October 19, 2021: “Myovant Sciences and Pfizer announced the presentation of new data from clinical studies of its once-daily relugolix combination therapy (relugolix 40 mg plus estradiol 1.0 mg and norethindrone acetate 0.5 mg) in premenopausal women with uterine fibroids and in women with endometriosis pain (an investigational use).
The data are being presented in oral sessions during the American Society for Reproductive Medicine (ASRM) 2021 Congress.
“These studies provide important new data for relugolix combination therapy, including detailed two-year efficacy and safety data in women with heavy menstrual bleeding associated with uterine fibroids from the Phase 3 LIBERTY studies,” said Juan Camilo Arjona Ferreira, M.D., Chief Medical Officer of Myovant Sciences, Inc.
“They also provide additional insight into the potential effect of relugolix combination therapy in women with pain associated with endometriosis.”
“These presentations also include the results of the first pooled analysis of data from the LIBERTY and SPIRIT studies, which strengthen our clinical understanding of relugolix combination therapy and its potential benefits for women with these common and often debilitating conditions,” said James Rusnak, M.D., Ph.D., Senior Vice President, Chief Development Officer, Internal Medicine and Hospital, Global Product Development at Pfizer.
Details of the presentations of data from the Phase 3 LIBERTY randomized withdrawal study of women with uterine fibroids are as follows:
LIBERTY Randomized Withdrawal Study: 2-Year Efficacy and Safety of Relugolix Combination Therapy in Women with Heavy Menstrual Bleeding Associated with Uterine Fibroids (Scientific Congress Prize Paper) This presentation reports on the results of the Phase 3 LIBERTY randomized withdrawal study, which was designed to evaluate the efficacy and safety of relugolix combination therapy for up to two years in premenopausal women with heavy menstrual bleeding associated with uterine fibroids who completed the 24-week LIBERTY 1 or 2 trials and the 28-week long-term extension study.
Effects of Relugolix Combination Therapy on Bone Mineral Density through 2 Years in Women with Heavy Menstrual Bleeding Associated with Uterine Fibroids This presentation shares data on changes in bone mineral density observed in the Phase 3 LIBERTY randomized withdrawal study, which reflects up to 104 weeks of treatment with relugolix combination therapy.
Details of the presentations of data from the SPIRIT 1 and 2 studies of women with pain associated with endometriosis are as follows:
Relugolix Combination Therapy Improves Multiple Dimensions of Quality of Life in Women with Endometriosis-Associated Pain: Results from the SPIRIT Program This presentation shares data on the potential effect of relugolix combination therapy on health-related quality of life domains, including emotional well-being, self-image and sense of control, which were assessed using the Endometriosis Health Profile (EHP)-30 questionnaire during the Phase 3 SPIRIT 1 and 2 studies.
Details of the presentations that assessed pooled data from both the LIBERTY and SPIRIT studies are as follows:
Assessment of Common Adverse Events of Relugolix Combination Therapy in Premenopausal Women Treated for Symptomatic Estrogen-Driven Conditions: LIBERTY and SPIRIT Studies This presentation shares data on the adverse events observed in premenopausal women on relugolix combination therapy, based on a pooled analysis of data from the LIBERTY 1/2 and SPIRIT 1/2 studies.
Integrated Long-Term Bone Mineral Density (BMD) Outcomes in Women Receiving Relugolix Combination Therapy in LIBERTY and SPIRIT Studies vs. Non-Treated Women This presentation reports on the results of a pooled assessment of data from the LIBERTY and SPIRIT studies and the LIBERTY long-term extension study, which analyzed bone mineral density outcomes in premenopausal women with uterine fibroids or endometriosis-associated pain.
In the U.S., relugolix combination tablet (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) is currently available as MYFEMBREE® for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women, with a treatment duration of up to 24 months.
The U.S. Food and Drug Administration (FDA) approved MYFEMBREE for this indication on May 26, 2021, based on data from the Phase 3 LIBERTY program.
Myovant and Pfizer are jointly developing and commercializing MYFEMBREE in the U.S. Relugolix combination therapy is under investigation for the use of pain in endometriosis; the efficacy and safety for this use have not been demonstrated.
On September 9, 2021, Myovant and Pfizer announced that the FDA accepted for review a supplemental New Drug Application (sNDA) for MYFEMBREE for the management of moderate to severe pain associated with endometriosis with a target action date of May 6, 2022.
About MYFEMBREE® MYFEMBREE (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) is the first once-daily oral treatment for heavy menstrual bleeding associated with uterine fibroids in premenopausal women approved by the U.S. Food and Drug Administration, with a treatment duration of up to 24 months.
MYFEMBREE contains relugolix, which reduces the amount of estrogen (and other hormones) produced by ovaries, estradiol (an estrogen) which may reduce the risk of bone loss, and norethindrone acetate (a progestin) which is necessary when women with a uterus (womb) take estrogen.
For full prescribing information including Boxed Warning and patient information, please click here.
Indications and Usage MYFEMBREE is indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. Limitations of Use: Use of MYFEMBREE should be limited to 24 months due to the risk of continued bone loss which may not be reversible.
Important Safety Information
BOXED WARNING: THROMBOEMBOLIC DISORDERS AND VASCULAR EVENTS
Estrogen and progestin combination products, including MYFEMBREE, increase the risk of thrombotic or thromboembolic disorders including pulmonary embolism, deep vein thrombosis, stroke and myocardial infarction, especially in women at increased risk for these events.
MYFEMBREE is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke or women with uncontrolled hypertension.
CONTRAINDICATIONS
MYFEMBREE is contraindicated in women with any of the following: high risk of arterial, venous thrombotic, or thromboembolic disorder; pregnancy; known osteoporosis; current or history of breast cancer or other hormone-sensitive malignancies; known hepatic impairment or disease; undiagnosed abnormal uterine bleeding; known hypersensitivity to components of MYFEMBREE.
WARNINGS AND PRECAUTIONS
Thromboembolic Disorders: Discontinue immediately if an arterial or venous thrombotic, cardiovascular, or cerebrovascular event occurs or is suspected.
Discontinue at least 4 to 6 weeks before surgery associated with an increased risk of thromboembolism, or during periods of prolonged immobilization, if feasible.
Discontinue immediately if there is sudden unexplained partial or complete loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis as these have been reported with estrogens and progestins.
Bone Loss: MYFEMBREE may cause a decrease in bone mineral density (BMD) in some patients, which may be greater with increasing duration of use and may not be completely reversible after stopping treatment.
Consider the benefits and risks in patients with a history of low trauma fracture or risk factors for osteoporosis or bone loss, including medications that may decrease BMD.
Assessment of BMD by dual-energy X-ray absorptiometry (DXA) is recommended at baseline and periodically thereafter. Consider discontinuing MYFEMBREE if the risk of bone loss exceeds the potential benefit.
Hormone-Sensitive Malignancies: Discontinue MYFEMBREE if a hormone-sensitive malignancy is diagnosed. Surveillance measures in accordance with standard of care, such as breast examinations and mammography are recommended.
Use of estrogen alone or estrogen plus progestin has resulted in abnormal mammograms requiring further evaluation.
Depression, Mood Disorders, and Suicidal Ideation: Promptly evaluate patients with mood changes and depressive symptoms including shortly after initiating treatment, to determine whether the risks of continued therapy outweigh the benefits.
Patients with new or worsening depression, anxiety, or other mood changes should be referred to a mental health professional, as appropriate.
Advise patients to seek immediate medical attention for suicidal ideation and behavior and reevaluate the benefits and risks of continuing MYFEMBREE.
Hepatic Impairment and Transaminase Elevations: Steroid hormones may be poorly metabolized in these patients.
Instruct women to promptly seek medical attention for symptoms or signs that may reflect liver injury, such as jaundice or right upper abdominal pain.
Acute liver test abnormalities may necessitate the discontinuation of MYFEMBREE use until the liver tests return to normal and MYFEMBREE causation has been excluded.
Gallbladder Disease or History of Cholestatic Jaundice: Discontinue MYFEMBREE if signs or symptoms of gallbladder disease or jaundice occur.
For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, assess the risk-benefit of continuing therapy. Studies among estrogen users suggest a small increased relative risk of developing gallbladder disease.
Elevated Blood Pressure: For women with well-controlled hypertension, monitor blood pressure and stop MYFEMBREE if blood pressure rises significantly.
Change in Menstrual Bleeding Pattern and Reduced Ability to Recognize Pregnancy: Advise women to use non-hormonal contraception during treatment and for one week after discontinuing MYFEMBREE.
Avoid concomitant use of hormonal contraceptives. MYFEMBREE may delay the ability to recognize pregnancy because it alters menstrual bleeding. Perform testing if pregnancy is suspected and discontinue MYFEMBREE if pregnancy is confirmed.
Risk of Early Pregnancy Loss: MYFEMBREE can cause early pregnancy loss. Exclude pregnancy before initiating and advise women to use effective non-hormonal contraception.
Uterine Fibroid Prolapse or Expulsion: Advise women with known or suspected submucosal uterine fibroids about the possibility of uterine fibroid prolapse or expulsion and instruct them to contact their physician if severe bleeding and/or cramping occurs.
Alopecia: Alopecia, hair loss, and hair thinning were reported in phase 3 trials with MYFEMBREE. Consider discontinuing MYFEMBREE if hair loss becomes a concern. Whether the hair loss is reversible is unknown.
Effects on Carbohydrate and Lipid Metabolism: More frequent monitoring in MYFEMBREE-treated women with prediabetes and diabetes may be necessary. MYFEMBREE may decrease glucose tolerance and result in increased blood glucose concentrations.
Monitor lipid levels and consider discontinuing if hypercholesterolemia or hypertriglyceridemia worsens.
In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations in triglycerides levels leading to pancreatitis. Use of MYFEMBREE is associated with increases in total cholesterol and LDL-C.
Effect on Other Laboratory Results: Patients with hypothyroidism and hypoadrenalism may require higher doses of thyroid hormone or cortisol replacement therapy.
Use of estrogen and progestin combinations may raise serum concentrations of binding proteins (e.g., thyroid-binding globulin, corticosteroid-binding globulin), which may reduce free thyroid or corticosteroid hormone levels. Use of estrogen and progestin may also affect the levels of sex hormone-binding globulin, and coagulation factors.
Hypersensitivity Reactions: Immediately discontinue MYFEMBREE if a hypersensitivity reaction occurs.
ADVERSE REACTIONS
Most common adverse reactions for MYFEMBREE (incidence ≥3% and greater than placebo) were hot flush/hyperhidrosis/night sweats, abnormal uterine bleeding, alopecia, and decreased libido. These are not all the possible side effects of MYFEMBREE.
DRUG INTERACTIONS
P-gp Inhibitors: Avoid use of MYFEMBREE with oral P-gp inhibitors. If use is unavoidable, take MYFEMBREE first, separate dosing by at least 6 hours, and monitor patients for adverse reactions.
Combined P-gp and Strong CYP3A Inducers: Avoid use of MYFEMBREE with combined P-gp and strong CYP3A inducers.
LACTATION Advise women not to breastfeed while taking MYFEMBREE.”
October 19, 2021: “The U.S. Food and Drug Administration issued a landmark proposal intended to improve access to and reduce the cost of hearing aid technology for millions of Americans.
The agency proposed a rule to establish a new category of over-the-counter (OTC) hearing aids. When finalized, the rule would allow hearing aids within this category to be sold directly to consumers in stores or online without a medical exam or a fitting by an audiologist.
The proposed rule is designed to help increase competition in the market while also ensuring the safety and effectiveness of OTC and prescription hearing aids.
Today’s action follows President Biden’s July Executive Order on Promoting Competition in the American Economy, which called for the FDA to take steps to allow hearing aids to be sold over the counter.
This effort also builds on the Biden-Harris Administration’s goal of expanding access to high-quality health care and lowering medical care costs for the American public.
“Reducing health care costs for everyone in America is a top priority,” said Health and Human Services Secretary Xavier Becerra.
“Today’s move by FDA takes us one step closer to the goal of making hearing aids more accessible and affordable for the tens of millions of people who experience mild to moderate hearing loss.”
Approximately 15% of American adults (37.5 million) age 18 and over report some trouble hearing.
However, despite the high prevalence and public health impact of hearing loss, only about one-fifth of people who could benefit from a hearing aid use one.
The proposed rule aims to address barriers to use, including cost, access, social stigma related to hearing loss, perceived value of the devices or certain state and federal regulations.
Many hearing aids can be expensive.
The rule aims to facilitate innovation and increase competition by lowering the barriers to entry for new hearing aid manufacturers. Under the proposed rule, hearing aids would be sold over the counter in more traditional brick-and-mortar retail stores or online (rather than doctors’ offices or specialty retail outlets) and will likely be less expensive than those currently sold – giving consumers greater choice at lower prices.
The proposed rule implements a key provision of the Over-the-Counter Hearing Aid Act, as enacted in the FDA Reauthorization Act of 2017. President Biden’s Executive Order on Competition included a timeline for action, and the FDA has now issued the proposed rule ahead of that schedule.
Hearing loss can be caused by aging, exposure to loud noises, certain medical conditions and other factors.
Individuals with permanent hearing loss can use hearing aids to help make speech and sounds around them louder, enabling more effective communication with others.
“Hearing loss has a profound impact on daily communication, social interaction and the overall health and quality of life for millions of Americans,” said Acting FDA Commissioner Janet Woodcock, M.D.
“The FDA’s proposed rule represents a significant step toward helping ensure that adults with mild to moderate hearing loss have improved access to more affordable and innovative product options.
The new regulatory category will provide the public with greater control over their hearing aid purchasing decisions at stores nationwide or online without the need for a professional hearing exam, fitting adjustment or a prescription.”
The proposed rule would also amend existing rules that apply to hearing aids for consistency with the new OTC category, repeal the conditions for sale for hearing aids and address state regulation of hearing aids.
The OTC category, when finalized, would apply to certain air-conduction hearing aids intended for adults age 18 and older who have perceived mild to moderate hearing loss.
Hearing aids for severe hearing loss or for users younger than age 18 would be prescription devices.
To ensure patient safety, the proposed rule also addresses a maximum output (volume) limit for OTC hearing aids that would prevent injuries from overamplification of sound.
In addition, the proposed rule includes certain device performance and design requirements, such as distortion control limits, self-generated noise limits, latency limits (how quickly an OTC hearing aid processes, amplifies and relays a sound), the range of frequencies that the device can reproduce and how uniformly the OTC hearing aid amplifies different frequencies over its bandwidth, as well as a requirement to limit the insertion depth of the device.
The proposed rule also includes labeling requirements for OTC hearing aids.
To coincide with the proposed rule, the FDA also issued an updated draft guidance, Regulatory Requirements for Hearing Aid Devices and Personal Sound Amplification Products (PSAPs).
The draft guidance describes hearing aids, PSAPs, their respective intended uses and regulatory requirements that apply to both types of products.
The draft guidance is intended to provide further clarification regarding the differences between PSAPs, which help people with normal hearing amplify sounds, and hearing aids and to inform consumers that PSAPs are not considered OTC alternatives for hearing aids.”
October 19, 2021: “The U.S. Food and Drug Administration announced it has authorized the marketing of four new oral tobacco products manufactured by U.S. Smokeless Tobacco Company LLC under the brand name of Verve.
Based on the FDA’s comprehensive review of available scientific evidence in the company’s premarket tobacco product applications (PMTAs), the agency determined the marketing of these products would be consistent with the statutory standard, “appropriate for the protection of the public health.”
This includes a review of data showing that youth, nonsmokers and former smokers are unlikely to initiate or reinitiate tobacco use with these products. The four products are: Verve Discs Blue Mint, Verve Discs Green Mint, Verve Chews Blue Mint, and Verve Chews Green Mint.
“Ensuring new tobacco products undergo a robust premarket evaluation by the FDA is a critical part of our mission to protect the public—especially kids.
While these are mint flavored products, data submitted to the FDA show the risk for youth uptake of these particular products is low, and stringent marketing restrictions will help prevent youth exposure,” said Mitch Zeller, J.D., director of the FDA’s Center for Tobacco Products.
“Importantly, evidence shows these products could help addicted smokers who use the most harmful combusted products completely switch to a product with potentially fewer harmful chemicals.”
The Verve products are oral tobacco products that contain nicotine derived from tobacco, but they do not contain cut, ground, powdered or leaf tobacco. All four products are chewed and then discarded, rather than swallowed, once the user is finished with the product.
The discs and chews differ in part by their texture. Both are flexible, but the discs are firm, and the chews are soft. These products are intended for adult tobacco users.
Before authorizing new tobacco products via the PMTA pathway, the FDA must, by law, take into consideration, among other things, the likelihood that current tobacco users will stop using tobacco products and the likelihood that current nonusers will start using tobacco products.
Research shows a low likelihood that youth, nonsmokers, or former smokers would initiate or reinitiate tobacco use with the Verve products.
Current users of Verve products and users who switch completely to Verve products are generally exposed to fewer harmful and potentially harmful constituents compared to cigarettes and other smokeless tobacco products.
The agency has posted the decision summary that further describes the basis for issuing marketing orders for these four products.
The marketing authorizations issued today allow the four tobacco products to be legally sold or distributed in the United States, but it does not mean the products are safe or “FDA approved,” as there are no safe tobacco products.
Additionally, the FDA is placing stringent restrictions on how Verve products are marketed, including via websites and through social media platforms, to help ensure that marketing targets only adults.
The FDA will evaluate new available data regarding the products through postmarketing records and reports required in the marketing order.
The company is required to regularly report to the FDA with information regarding the products on the market, including, but not limited to, ongoing and completed consumer research studies, advertising, marketing plans, sales data, information on current and new users, manufacturing changes and adverse experiences.
The FDA will withdraw a marketing order if it determines that the continued marketing of a product is no longer appropriate for the protection of the public health, for example, as a result of significant uptake of the product by youth.
The agency continues to conduct premarket review of thousands of tobacco product applications and remains committed to communicating with the public about progress, including the issuance of marketing denial orders for more than one million flavored e-cigarette products that lacked sufficient evidence that they have a benefit to adult smokers sufficient to overcome the public health concern posed by the well-documented and considerable appeal of such products to youth.”
October 18, 2021: “The U.S. FDA approved the first interchangeable biosimilar product to treat certain inflammatory diseases.
Cyltezo (adalimumab-adbm), originally approved in August 2017, is both biosimilar to, and interchangeable with (may be substituted for), its reference product Humira (adalimumab) for Cyltezo’s approved uses.
Cyltezo is the second interchangeable biosimilar product approved by the agency and the first interchangeable monoclonal antibody. Once on the market, approved biosimilar and interchangeable biosimilar products can play a role in facilitating access to treatments for many serious health conditions.
“The biosimilar and interchangeable approval pathway was created to help increase access to treatment options for patients with serious medical conditions,” said Acting FDA Commissioner Janet Woodcock, M.D.
“We continue to be steadfast in our commitment to provide patients with alternative high-quality, affordable medications that are proven to be safe and effective.”
Cyltezo is approved for the following indications in adult patients:
moderately to severely active rheumatoid arthritis;
active psoriatic arthritis;
active ankylosing spondylitis (an arthritis that affects the spine);
moderately to severely active Crohn’s disease;
moderately to severely active ulcerative colitis; and
moderate to severe chronic plaque psoriasis.
Cyltezo is also indicated for moderately to severely active polyarticular juvenile idiopathic arthritis in patients two years of age and older, and pediatric patients six years of age or older with Crohn’s disease.
Biological products, generally derived from a living organism, include medications for treating many serious illnesses and chronic health conditions.
A biosimilar is a biological product that is highly similar to, and has no clinically meaningful differences from, a biological product already approved by the FDA (also called the reference product).
Patients can expect the same safety and effectiveness from the biosimilar as they can from the reference product. Interchangeable biosimilar products can be expected to produce the same clinical result as the reference product in any given patient and, for biological products administered more than once to an individual, the risk in terms of safety or diminished efficacy of switching between the two products is not greater than the risk of using the reference product without such switching.
An interchangeable biosimilar product may be substituted for the reference product without the prescriber having to change the prescription.
The substitution may occur at the pharmacy, subject to state pharmacy laws which vary by state, a practice commonly called “pharmacy-level substitution” — similar to how generic drugs are substituted for brand name drugs. Biosimilar and interchangeable biosimilar products may cost less than the brand-name medicine.
Cyltezo, offered in a single-dose, pre-filled glass syringe (40 mg/0.8 mL, 20 mg/0.4 mL), is administered subcutaneously (under the skin) under the guidance of a physician.
The most serious known side effects with Cyltezo are infections and malignancies (cancers). The most common expected adverse reactions are upper respiratory and sinus infections, injection site reactions, headache and rash.
Like Humira, the labeling for Cyltezo contains a boxed warning to alert health care professionals and patients about an increased risk of serious infections that may lead to hospitalization or death.
The boxed warning also notes that lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including adalimumab products.
The drug must be dispensed with a patient Medication Guide that describes important information about its uses and risks.
The FDA granted approval of Cyltezo to Boehringer Ingelheim on October 15, 2021.
To date, the FDA has approved 31 biosimilar products, including two interchangeable products, for a variety of health conditions.”
October 15, 2021: “Silence Therapeutics plc, a leader in the discovery, development and delivery of novel short interfering ribonucleic acid (siRNA) therapeutics for the treatment of diseases with significant unmet medical need announces:
– the Company’s intention to cancel the admission of its ordinary shares of nominal value £0.05 each (the “Ordinary Shares“) to trading on AIM (the “AIM Delisting“), subject to shareholder approval, with effect from 30 November 2021.
Subject to shareholder approval, the Company’s last day of trading on AIM will be 29 November 2021. Silence will retain the listing on the Nasdaq Global Market (“Nasdaq“) of American Depositary Shares, each representing three Ordinary Shares (the “ADSs“), under ticker symbol “SLN”.
The Company expects Nasdaq to become the primary trading venue for its equity securities. Existing holders of ADSs not also holding Ordinary Shares do not need to take any action in relation to the AIM Delisting;
– the posting of a circular to shareholders (the “Circular“) which contains further information on the AIM Delisting and the process to deposit Ordinary Shares for delivery of ADSs and notice of a general meeting to be held on 1 November 2021 at 72 Hammersmith Road, London W14 8TH at 2.00 p.m. (London time) (the “General Meeting“) at which shareholder approval will be sought, inter alia, for the AIM Delisting; and
– the intention to today file with the U.S. Securities and Exchange Commission (the “SEC“) a shelf registration statement on Form F-3 (the “Registration Statement“) pursuant to which the Company may offer and sell up to $300,000,000 of its Ordinary Shares in the form of ADSs including the intention to enter into a sales agreement (the “Sales Agreement“) with a sales agent (the “Sales Agent“), pursuant to which the Company may sell, from time to time, at its option, up to $100,000,000 of ADSs through the Sales Agent (the “ATM Program“) in “at the market” transactions on Nasdaq.
The Proposed AIM Delisting and the General Meeting
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· Following the AIM Delisting, the Company’s ADSs will remain listed on Nasdaq, which will become the primary trading venue for its equity securities, and securities in the Company will only be publicly tradeable in the form of Nasdaq-listed ADSs.
· The board of directors of the Company (the “Board” and the “Directors“) believes that the AIM Delisting should enhance the liquidity of trading in the Company’s ADSs as all such trading will be concentrated in a single venue.
· The Company is providing an opportunity for shareholders to deposit their Ordinary Shares with the Company’s ADS depositary in exchange for delivery of ADSs, without cost, in connection with the AIM Delisting whether prior, on, or subsequent to 30 November 2021 (being the date on which the AIM Delisting takes effect), except that the Depositary has not agreed to waive that fee with respect to more than 81,831,467 Ordinary Shares, which is the number of Ordinary Shares that were in issue but not represented by ADSs on 15 October 2021 and has not agreed to waive fees on any deposit made by the Company.
Mark Rothera, President and Chief Executive Officer of Silence Therapeutics, said: “This marks a very important step in the evolution of our company and positions Silence as a global RNAi leader.
With our mRNAi GOLD™ platform advancing in the clinic, we see substantial opportunity to build value over the next 12 months and longer term. We are grateful to have the continued support of our loyal shareholders and look forward to this exciting new chapter of growth.”
Craig Tooman, Chief Financial Officer of Silence Therapeutics, said: “A key priority for us has been to create a more attractive and efficient trading mechanism for our shareholders and to support increasing interest from new investors. We believe the move to trade exclusively on the Nasdaq – a top global exchange – accomplishes that objective.
This is an exciting time for Silence and we look forward to continuing to expand our global shareholder base.”
The Company will today be posting the Circular to shareholders which will set out further information on the process to deposit Ordinary Shares for delivery of ADSs, including personalised forms for those holders of certificated Ordinary Shares who wish to deposit their Ordinary Shares for delivery of ADSs, as well as containing the notice of General Meeting.
Copies will also be available on Silence’s website at www.silence-therapeutics.com.
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The Company was incorporated in 1994 and its Ordinary Shares have been admitted to trading on AIM since 1995. In September 2020, the Company undertook a direct listing of ADSs representing its Ordinary Shares on the Nasdaq Capital Market.
In February 2021, the Company announced an oversubscribed private placement of ADSs for gross proceeds of approximately $45 million. In June 2021, the Company moved its Nasdaq listing from the Nasdaq Capital Market tier to the Nasdaq Global Market tier.
As at 13 October 2021, being the last practicable date prior to the date of this announcement, approximately 8.9 per cent. of the Company’s Ordinary Shares are represented by ADSs tradeable on Nasdaq.
All shareholders who have not already deposited their Ordinary Shares for delivery of ADSs are currently able to do so at any time. Affiliates of the Company who deposit their ordinary shares may be subject to limitations on resale of ADSs under U.S. securities law.
The Company intends to convert an existing secondary resale shelf registration statement on Form F-1 to a short-form registration statement on Form F-3, which will, upon effectiveness, continue to grant such affiliates the ability to freely resell such restricted securities without restriction.
The AIM Rules for Companies published by London Stock Exchange plc (the “London Stock Exchange“) (the “AIM Rules for Companies“) require that, unless the London Stock Exchange otherwise agrees, the cancellation of a company’s shares from trading on AIM requires the consent of not less than 75 per cent. of votes cast by its shareholders given in a general meeting. Notwithstanding that the Company may be able to seek the agreement of the London Stock Exchange that shareholder consent in general meeting is not required due to the listing of ADSs on Nasdaq, the Board has determined to seek shareholder approval for the proposed AIM Delisting.
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The Board has decided to implement the AIM Delisting for the following reasons:
· The AIM Delisting is expected to further enhance the liquidity of trading in the Company’s securities by combining on Nasdaq the volume of transactions from both Nasdaq and AIM.
· Having securities solely listed on Nasdaq, rather than dual-listed on Nasdaq and AIM as is the case at present, is expected to increase the willingness of US-based investors to invest in the Company’s securities.
· A Nasdaq-only listing structure provides for a streamlined operation that showcases the global nature of the Company’s scope and places it more clearly within the ranks of international biotechnology companies that are its true peers.
· The cost of complying with the AIM Rules for Companies is incremental to that for complying with the Nasdaq market rules and the Company sees advantages in reducing its cost base as it progresses its clinical programmes and commercial strategy.
· Internal financial and legal staff time spent on compliance with the AIM Rules for Companies is incremental to that required for compliance with the Nasdaq market rules.
· ADSs representing the Company’s Ordinary Shares will remain tradeable on Nasdaq.
Accordingly, the Directors believe that it is no longer in the best interests of the Company or its shareholders as a whole for the Company to retain admission of its Ordinary Shares to trading on AIM.
However, the Company is providing an opportunity for shareholders to deposit their Ordinary Shares with the Company’s ADS depositary in exchange for delivery of ADSs, without cost, in connection with the AIM Delisting whether prior, on, or subsequent to 30 November 2021 (being the date on which the AIM Delisting takes effect), except that the Depositary has not agreed to waive that fee with respect to more than 81,831,467 Ordinary Shares, which is the number of Ordinary Shares that were in issue but not represented by ADSs on 15 October 2021 and has not agreed to waive fees on any deposit made by the Company.
Effect of the AIM Delistingclose preference sidebar
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If the resolutions are passed at the General Meeting, Shareholders will no longer be able to buy and sell Ordinary Shares on AIM after 29 November 2021. Holders of Ordinary Shares should read “Information for holders of Ordinary Shares” below which explains in more detail the process of depositing Ordinary Shares for delivery of ADSs.
As a company incorporated in England and Wales, the Company will continue to be subject to the requirements of the Companies Act 2006.
Following the AIM Delisting taking effect, the Company will no longer be subject to the AIM Rules for Companies or be required to retain the services of an independent nominated adviser.
The Company will also no longer be subject to the QCA Corporate Governance Code or be required to comply with the continuing obligations set out in the Disclosure Guidance and Transparency Rules (the “DTRs“) of the Financial Conduct Authority (the “FCA“) or, provided the Company’s securities remain outside the scope of the regulation, UK MAR.
In addition, the Company and its shareholders will no longer be subject to the provisions of the DTRs relating to the disclosure of changes in significant shareholdings in the Company.
The Company intends to continue to comply with all regulatory requirements for the Nasdaq listing of ADSs, including all applicable rules and regulations of the SEC.
Shareholders who continue to hold Ordinary Shares following the AIM Delisting will continue to be notified of the availability of key documents on the Company’s website, including publication of annual reports and annual general meeting documentation.
Holders of ADSs will be able to continue to access all such information via the Silence website.
Holders of Ordinary Shares and ADSs will remain entitled to receive any future dividends that may be declared thereon, which dividends will also accrue to ADS holders in accordance with the terms of the Deposit Agreement.
Application of the City Code following the AIM Delistingclose preference sidebar
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Following the AIM Delisting, as the Company will remain a public limited company incorporated in England and Wales but its securities will not be admitted to trading on a regulated market or multilateral trading facility in the United Kingdom (or a stock exchange in the Channel Islands or the Isle of Man), the City Code on Takeovers and Mergers (the “City Code“) will only apply to the Company if it is considered by the Panel on Takeovers and Mergers (the “Panel“) to have its place of central management and control in the United Kingdom (or the Channel Islands or the Isle of Man). This is known as the “residency test”.
The way in which the test for central management and control is applied for the purposes of the City Code may be different from the way in which it is applied by the United Kingdom tax authorities, Her Majesty’s Revenue & Customs (“HMRC“).
Under the City Code, the Panel looks to where the majority of the directors of the Company are resident, amongst other factors, for the purposes of determining where the Company has its place of central management and control.
The Panel has confirmed to the Company that following the AIM Delisting, based on the current composition of the Board, the City Code will continue to apply to the Company.
However, the City Code could cease to apply to the Company in the future if any changes to the Board composition result in the majority of the Directors not being resident in the United Kingdom, Channel Islands and Isle of Man.
Further details of the Panel, the City Code and the protections given by the City Code are set out in the Circular.
Shareholders are encouraged to read this information carefully as it outlines certain important protections which they will be giving up if they agree to the AIM Delisting and the Company subsequently ceases to be subject to the City Code.
The Board is seeking shareholder approval to an amendment to the Company’s articles of association (the “Articles“) which would apply in the event that the City Code ceased to apply to the Company.
This amendment would insert a new article 159 into the Articles which would apply in the event that the City Code were no longer to apply to the Company.
Article 159 includes certain takeover protections so that the Company is able to defend itself and its shareholders from hostile takeovers.
An ordinary resolution will be put to shareholders at each annual general meeting, starting with the annual general meeting in 2022, as to whether article 159 should continue to apply for the period until the next following annual general meeting.
The full text of article 159 is set out in Appendix B to the Circular.
Information for holders of Ordinary Sharesclose preference sidebar
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If the resolutions are passed at the General Meeting, the Company’s Ordinary Shares will continue to be traded on AIM until market close (4.30 p.m. London time) on 29 November 2021.
Thereafter, holders of Ordinary Shares can still hold the Ordinary Shares, but there will be no public market in the United Kingdom on which the Ordinary Shares can be traded, and the Ordinary Shares will not be tradeable on Nasdaq in this form.
To sell Ordinary Shares on a public market following the AIM Delisting, shareholders will need to deposit their Ordinary Shares for delivery of ADSs.
Each ADS represents three Ordinary Shares.
This deposit can be made at any time, including before the AIM Delisting, subject in all cases to the provisions of, and the limitations set forth in, the New York law governed deposit agreement dated 4 September 2020 between the Company, the Bank of New York Mellon (the “Depositary“) and all holders and beneficial owners of ADSs issued thereunder (the “Deposit Agreement“).
The Board considers that shareholders should consider depositing their Ordinary Shares for delivery of ADSs prior to the AIM Delisting on 30 November 2021 for the following reasons:
· For those shareholders who hold their Ordinary Shares in certificated form and wish to deposit their Ordinary Shares for delivery of ADSs, the Company’s Receiving Agent, Link Group, will facilitate, on the Company’s behalf, a block transfer process.
Shareholders who hold their Ordinary Shares in certificated form will find enclosed with the Circular a personalised block transfer participation request form for use if they wish to deposit their Ordinary Shares for delivery of ADSs.
Subject to the requisite documents being returned to Link Group by the required deadline (being 1.00 p.m. on 3 November 2021), Link Group will arrange for the relevant Ordinary Shares to be transferred to and through Link Group’s CREST account to the CREST account of the Custodian, which has been appointed by the Depositary, The Bank of New York Mellon, to safe keep the Ordinary Shares upon deposit, so that the Depositary can arrange to deliver the corresponding number of ADSs.
The Custodian, on behalf of the Depositary, will hold all deposited Ordinary Shares in a custody account for the benefit of the holders and beneficial owners of ADSs.
· Shareholders who elect to deposit their Ordinary Shares for delivery of ADSs prior to the AIM Delisting will not incur a UK stamp duty, or SDRT, charge.
However, it is expected that shareholders who elect to deposit their Ordinary Shares for delivery of ADSs following the AIM Delisting will incur a stamp duty, or SDRT, charge, at a rate of 1.5 per cent. of the market value of the Ordinary Shares being deposited, to the UK taxation authority, HMRC.
· Ordinarily, shareholders who deposit their Ordinary Shares for delivery of ADSs are charged an ADS issuance fee, by the Depositary, of up to $5.00 per 100 ADSs or portion thereof.
However, no ADS issuance fees will be charged to shareholders who elect to deposit their Ordinary Shares in connection with the AIM Delisting whether prior, on, or subsequent to 30 November 2021 (being the date on which the AIM Delisting takes effect), except that the Depositary has not agreed to waive that fee with respect to more than 81,831,467 Ordinary Shares, which is the number of Ordinary Shares that were in issue but not represented by ADSs on 15 October 2021 and has not agreed to waive fees on any deposit made by the Company.
· Otherwise than in connection with the AIM Delisting, ADS issuance fees of up to $5.00 per 100 ADSs or portion thereof will be charged by the Depositary in connection with any future deposits of Ordinary Shares.
· Ordinary Shares may be deposited for delivery of ADSs only in multiples of three Ordinary Shares. It is not possible to receive a fraction of an ADS, so in the event that the deposit is completed after the AIM Delisting, there is a risk that shareholders will be left with a small number of Ordinary Shares (up to a maximum of two shares) which cannot be deposited for delivery of ADSs.
If the deposit is made before the AIM Delisting has taken effect, any residual Ordinary Shares can be sold by shareholders on AIM prior to, and including, 29 November 2021 so long as those Ordinary Shares are in uncertificated form.
Shareholders who hold their Ordinary Shares in certificated form may elect to donate their residual shares to the charity Share Gift by making that election on their personalised block transfer participation request form.
Shareholders who do not elect to participate in the block transfer process can utilise the services of a broker who is able to facilitate deposits of Ordinary Shares at the shareholder’s convenience.
Shareholders whose Ordinary Shares are held in uncertificated form in CREST and who wish to deposit their Ordinary Shares for delivery of ADSs, should contact their broker without delay to request that their Ordinary Shares are deposited.
Silence advises holders of Ordinary Shares to seek independent financial advice regarding the AIM Delisting and the deposit of their Ordinary Shares for delivery ADSs.
Information on the process to deposit Ordinary Shares for delivery of ADSs and the forms to be completed accompany the Circular.
The information and forms, and contacts at the Company’s Receiving Agent, Link Group, in respect of completion of the block transfer participation request form for certificated holders, and the Depositary, The Bank of New York Mellon, are included on Silence’s website at www.silence-therapeutics.com.
If the Resolutions are not passed at the General Meeting, all documents provided to Link Group and/or The Bank of New York Mellon in relation to the deposit of Ordinary Shares for delivery of ADSs shall be of no effect and all original share certificates will be returned to shareholders by Link Group.
UK tax treatmentclose preference sidebar
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Many investors purchase AIM-quoted shares because they are classed as unlisted/unquoted securities which may qualify individuals who are UK tax resident and UK domiciled for relief from inheritance taxation and certain other preferential tax benefits.
Silence cannot and does not provide any form of taxation advice to shareholders and therefore shareholders are strongly advised to seek their own taxation advice to confirm the consequences of continuing to hold unlisted Ordinary Shares or depositing Ordinary Shares for delivery of ADSs.
The following summary does not constitute legal or tax advice and is not exhaustive. The Company’s understanding of the current position for UK individuals who are UK domiciled for relevant tax purposes is as follows but it should be noted that the position on certain points is not free from uncertainty and that the Company has not taken steps to confirm the current position with HMRC.
Therefore, the following should not be relied upon by shareholders without taking further advice (and the Company accepts no liability in respect of any such reliance on any information provided herein on taxation matters):
· The AIM Delisting should not prevent the Ordinary Shares from qualifying as unlisted/unquoted securities for the purposes of certain specific UK tax rules (notably, the UK inheritance tax business property relief rules).
Accordingly, it is expected that HMRC should accept that those shareholders who elect to continue to hold unlisted Ordinary Shares should continue to be regarded as holding unlisted/unquoted securities under those same rules.
· Under HMRC’s stated practice those shareholders who elect to deposit their holdings of Ordinary Shares for delivery of Nasdaq-listed ADSs should not be considered as disposing of the Ordinary Shares for UK capital gains tax purposes when transferring the shares to the Depositary, The Bank of New York Mellon, in exchange for issue of ADSs on the basis that the shareholder retains beneficial ownership of the Ordinary Shares.
Shareholders who elect to deposit their holdings of Ordinary Shares for delivery of Nasdaq-listed ADSs prior to the AIM Delisting should not incur a stamp duty, or SDRT, charge.
It is expected that shareholders who elect to deposit their holdings of Ordinary Shares for delivery of Nasdaq-listed ADSs following the AIM Delisting may incur a stamp duty, or SDRT, charge at the rate of 1.5 per cent. of the market value of the Ordinary Shares being deposited.
It is strongly recommended that shareholders obtain appropriate professional advice in respect of these and other taxes.
Further information in relation to the AIM Delistingclose preference sidebar
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The Board believes that the proposed AIM Delisting is an appropriate next step for the Company and is in the best interests of shareholders as a whole.
Further information about the process required to deposit Ordinary Shares for delivery of ADSs tradeable on Nasdaq, together with a set of Frequently Asked Questions, accompany the Circular.
Details of the General Meeting and action to be taken in respect of the General Meetingclose preference sidebar
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A notice convening the General Meeting, which is to be held at 72 Hammersmith Road, London W14 8TH at 2.00 p.m. (London time) on 1 November 2021 is set out in the Circular.
At the time of publication of the notice of General Meeting, it is anticipated that the General Meeting will proceed as an open meeting.
However, given ongoing uncertainty, and bearing in mind the broader public health considerations and for the safety of others, the Board will continue to monitor government guidance in relation to the COVID-19pandemic, and if any changes to the arrangements set out in the notice of General Meeting are required, this will be communicated via a regulatory information service and the Company’s website.
Expected timetable for the AIM Delistingclose preference sidebar
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Dispatch of the Circular and the enclosed documents
15 October 2021
Latest date for receipt of proxy voting instructions and (if applicable) hard copy forms of proxy
2.00 p.m. on 28 October 2021
General Meeting
2.00 p.m. on 1 November 2021
Last date for receipt by Link Group from certificated shareholders of duly completed block transfer participation request forms and original share certificates
3 November 2021 at 1.00 p.m.
Last date for receipt by The Bank of New York Mellon from CREST holders of duly completed issuance forms
17 November 2021 at 3.00 p.m.
Expected date of issuance of ADSs to block transfer participants
24 November 2021
Expected date of posting of ADS confirmations to shareholders by The Bank of New York Mellon
24 November 2021
Last day of dealings in the Ordinary Shares on AIM
29 November 2021
Cancellation of admission to trading on AIM of the Ordinary Shares
30 November 2021 at 7.00 a.m.
Notes
(1) References to time in this announcement are to London time unless otherwise stated.
(2) Each of the times and dates in the above timetable are subject to change. If any of the above times and/or dates change, the revised times and/or dates will be notified to shareholders by announcement through a Regulatory Information Service.
(3) All steps after the General Meeting are dependent on the resolutions being passed at the General Meeting. If the resolutions are not passed at the General Meeting, all documents provided to Link Group and/or The Bank of New York Mellon in relation to the deposit of Ordinary Shares for delivery of ADSs shall be of no effect and all original share certificates will be returned to shareholders by Link Group.
SEC Registration Statement on Form F-3 and the ATM Program
The Company intends to today file the Registration Statement with the SEC, pursuant to which the Company may offer up to $300,000,000 of its Ordinary Shares in the form of ADSs, with each ADS representing three Ordinary Shares.
In connection with the Registration Statement, the Company also intends to enter into the Sales Agreement with the Sales Agent, in connection with the ATM Program.
Any Ordinary Shares to be represented by ADSs sold under the ATM Program will be allotted and issued pursuant to the resolutions adopted at the Company’s annual general meeting on 15 June 2021 and/or any replacement resolutions to allot and issue Ordinary Shares adopted by the Company’s shareholders from time to time.
The ADSs intended to be sold under the Sales Agreement, if any, will be issued and sold by methods deemed to be an “at the market offering” as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended, or in negotiated transactions, if authorised by the Company, in each case, pursuant to the Registration Statement.
The Registration Statement will contain a prospectus relating to the ATM Program pursuant to which any sales under the ATM Program will be made following the effectiveness of the Registration Statement.
Following the filing of the Registration Statement, it will not become effective until declared so by the SEC. These securities may not be sold nor may offers to buy be accepted prior to the time the Registration Statement becomes effective.
Once filed, a copy of the Registration Statement and the prospectus supplement relating to the ATM Program may be obtained on the SEC’s website at www.sec.gov.
The intended filing of the Registration Statement does not affect the statutory pre‐emption rights of shareholders in the Company.
Block Admission Application
Application will be made to the London Stock Exchange for a block admission (‘Block Admission‘) of 17,879,768 new ordinary shares of nominal value £0.05 each (the “New Ordinary Shares“) which may be allotted and issued in connection with the ATM Program, prior to the AIM Delisting becoming effective.
It is expected that the Block Admission will become effective on or around 20 October 2021.
The Block Admission, representing approximately 20% of the current issued share capital, is being made for the allotment and issue of any New Ordinary Shares arising from the issuance of ADSs in connection with the ATM Program prior to the AIM Delisting becoming effective:
If and when issued, the New Ordinary Shares will rank pari passu in all respects with the existing Ordinary Shares in the Company.
Prior to the AIM Delisting becoming effective, the Company will notify on a monthly basis when there are changes to the issued share capital of the Company, and these monthly figures may be used by shareholders as the denominator for the calculation by which they will determine if they are required to notify their interest in, or a change in their interest in, the share capital of the Company.
The Company will also make six-monthly announcements regarding the utilisation of the Block Admission in accordance with rule 29 of the AIM Rules for Companies.”
Pfizer Inc. (NYSE: PFE) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the 100 mg and 200 mg doses of abrocitinib, an oral, once-daily, Janus kinase 1 (JAK1) inhibitor, for marketing authorization to treat moderate to severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. The CHMP also adopted a positive opinion recommending an extension to the existing indications for XELJANZ® (tofacitinib) for the treatment of adults with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy.
“The CHMP’s positive recommendation brings us closer to our goal of helping people living with moderate to severe atopic dermatitis in Europe find relief,” said Michael Corbo, PhD, Chief Development Officer, Inflammation & Immunology, Pfizer Global Product Development. “We look forward to working with the European Commission and hope to soon provide abrocitinib to people in Europe and eventually to more people worldwide who are living with this debilitating disease, many of whom have limited treatment options today.”
“Atopic dermatitis can be a debilitating condition that impacts the daily lives of millions of people,” said Dr. Diamant Thaci, Comprehensive Center for Inflammation Medicine, University of Luebeck, Germany. “Abrocitinib has shown significant efficacy, including relief from the hallmark chronic itch, rapid improvements in skin clearance, extent and severity of disease versus placebo, and a favorable risk-benefit profile. If approved, abrocitinib may become an important new treatment option for patients living with moderate to severe atopic dermatitis.”
Based on these CHMP recommendations, a decision by the European Commission, which authorizes marketing approval in the European Union, is expected on the abrocitinib and XELJANZ applications later this year. If granted by the European Commission, the centralized marketing authorizations would be valid in all EU Member States as well as in Iceland, Liechtenstein, and Norway.
The recommendation for abrocitinib is based on the results of five Phase 3 studies and a long-term extension study from a robust clinical trial program including more than 3,100 patients.
The recommendation for XELJANZ is based on data from a Phase 3, multicenter, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of XELJANZ twice daily versus placebo in 269 adult patients living with active AS.
About Abrocitinib Abrocitinib is an oral small molecule that selectively inhibits Janus kinase (JAK) 1. Inhibition of JAK1 is thought to modulate multiple cytokines involved in pathophysiology of atopic dermatitis, including interleukin IL-4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin (TSLP).
CIBINQO® (abrocitinib) received marketing authorization from the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Japanese Ministry of Health, Labour and Welfare (MHLW) in September 2021.
About XELJANZ XELJANZ is approved in the European Union in four indications: adults with moderately to severely active rheumatoid arthritis (RA) after disease modifying antirheumatic drug (DMARD) failure or intolerance, adults with active psoriatic arthritis (PsA) after DMARD failure or intolerance, adults with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent, and active polyarticular juvenile idiopathic arthritis (JIA) and juvenile PsA in patients two years of age and older who have responded inadequately to previous therapy with DMARDs. Limitations of Use below.
XELJANZ has been studied in more than 50 clinical trials worldwide and prescribed to more than 300,000 adult patients (the majority of whom were RA patients) worldwide since 2012.i,ii.
In June 2021, the Committee for Medicine Products for Human Use of the European Medicines Agency adopted a recommendation from the Pharmacovigilance Risk Assessment Committee (PRAC) following its review of XELJANZ in the European Union, which states that in patients over 65 years of age, patients who are current or past smokers, patients with other cardiovascular (CV) risk factors, and patients with other malignancy risk factors, XELJANZ should only be used if no suitable treatment alternatives are available. The CHMP-endorsed PRAC recommendation is applicable to all EU member states and has been implemented in the XELJANZ summary of product characteristics.
Pfizer is also continuing to work with the U.S. Food and Drug Administration (FDA) and other regulatory agencies to review the full results and analysis of the ORAL Surveillance data.
Most recently in September 2021, the FDA issued a Drug Safety Communication (DSC) related to XELJANZ®/XELJANZ XR® and two other arthritis medicines in the same drug class, based on its completed review of the ORAL Surveillance trial.
About Atopic Dermatitis AD is a chronic skin disease characterized by inflammation of the skin and skin barrier defects.
Lesions of AD are characterized by erythema (skin turning red or purple depending on normal skin color), itching, induration (hardening)/papulation (formulation of papules), and oozing/crusting.
AD affects up to 10% of adults worldwide.v The prevalence of AD in adults in the European Union is approximately 5-10%.”
October 15, 2021: “Positive high-level results from the HIMALAYA Phase III trial showed a single, high priming dose of tremelimumab added to Imfinzi (durvalumab) demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit versus sorafenib as a 1st-line treatment for patients with unresectable hepatocellular carcinoma (HCC) who had not received prior systemic therapy and were not eligible for localised treatment.
This novel dose and schedule of tremelimumab, an anti-CTLA4 antibody, and Imfinzi is called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab).
The combination demonstrated a favourable safety profile, and the addition of tremelimumab to Imfinzi did not increase severe hepatic toxicity.
Imfinzi alone demonstrated non-inferior OS to sorafenib with a numerical trend in favour of Imfinzi and an improved tolerability profile compared to sorafenib.
Liver cancer, of which HCC is the most common type, is the third leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide with approximately 900,000 people diagnosed each year.Only 7% of patients with advanced disease survive five years.
Ghassan Abou-Alfa, MD, MBA, Attending Physician at Memorial Sloan Kettering Cancer Center and principal investigator in the HIMALAYA Phase III trial, said: “HIMALAYA is the first Phase III trial to add a novel single priming dose of an anti-CTLA4 antibody to another checkpoint inhibitor, durvalumab.
This serves to boost the patient’s own immune system against their liver cancer, aiming to maximise long-term survival with minimal side effects. This is very exciting news for our patients.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Inhibition of CTLA-4 has shown the ability to drive benefit particularly in the tail of the survival curve in several settings.
This is the first time a dual immunotherapy regimen has improved overall survival as a 1st-line treatment for patients with unresectable liver cancer for whom treatment options are limited and long-term outcomes are poor.”
The data from the HIMALAYA Phase III trial will be presented at a forthcoming medical meeting.
Imfinzi and tremelimumab were granted Orphan Drug Designations in the US for the treatment of HCC in 2020. Tremelimumab was also granted orphan designation in the EU in HCC in 2020.”
October 14, 2021: “The U.S. FDA announced it has awarded 11 new clinical trial research grants, equaling more than $25 million of funding over the next four years.
The FDA’s Congressionally-funded Orphan Products Grants Program awards these grants to clinical investigators to support the development of medical products for patients with rare diseases.
“Supporting the development and evaluation of new treatments for rare diseases is a critical part of the FDA’s mission,” said Acting FDA Commissioner Janet Woodcock, M.D.
“These grants are the latest examples of the FDA’s ongoing commitment to help meet the future and current health needs of those who suffer from a rare disease.”
The grant awards support clinical studies of products that address unmet needs in rare diseases or conditions or provide highly significant improvements in treatment or diagnosis.
Many of these studies involve children, as young as newborns, including one evaluating the treatment of a rare inherited skin disease known as recessive dystrophic epidermolysis bullosa, or RDEB, a condition that can lead to painful blisters and wounds that are often disfiguring and fatal.
Another study seeks to evaluate early treatment before the onset of seizures in infants with tuberous sclerosis complex, which is an inherited disease that can affect a variety of organs and can result in long term brain development issues.
This grant also includes an innovative demonstration project that will utilize a collaborative approach to evaluate a tool with the potential to improve data accuracy for clinical trials taking place at more than one location.
Some of the new awards fund clinical studies of products for use in brain cancers. Specifically, one will evaluate a novel peptide vaccine to treat pediatric brain cancers.
The vaccine is designed to be directed specifically to areas of tumor in the brain and has the potential to significantly impact the way these rare and deadly tumors are treated.
“The Office of Orphan Products Development works to identify, examine and ultimately fill the gaps that exist within the rare disease drug development community by funding necessary and revolutionary clinical studies to determine the safety and efficacy of potential treatment options,” said Sandra Retzky, D.O., J.D., MPH, director of OOPD.
“These grants demonstrate the FDA’s commitment to supporting the development of new treatments for patients living with rare diseases.”
Below is a complete list of the grants in alphabetical order:
Armgo Pharma, INC. (Ardsley, New York); Eugene Marcantonio; Phase 2 study of S48168 (ARM210) for the treatment of catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1); $1 million over two years
Boston Children’s Hospital (Boston, Massachusetts); Mark Puder; Phase 3 study of RELiZORB for the treatment of short bowel syndrome; $2.7 million over four years
Castle Creek Biosciences, LLC (Exton, Pennsylvania); Mary Spellman; Phase 3 study of FCX-007 (genetically modified autologous human dermal fibroblasts) for the treatment of recessive dystrophic epidermolysis bullosa; $1.8 million over four years
Cincinnati Children’s Hospital Medical Center (Cincinnati, Ohio); Darcy Krueger; Phase 2b study of sirolimus for the prevention of epilepsy in patients with tuberous sclerosis complex; $5 million over four years
Cincinnati Children’s Hospital Medical Center; Michael Jordan; Phase 2 study of abatacept for the treatment of common variable immunodeficiency with interstitial lung disease (ABCVILD); $3.1 million over four years
Duke University (Durham, North Carolina); Eric Thompson; Phase 2 study of peptide vaccine targeting CMV antigen for the treatment of newly diagnosed pediatric high-grade glioma and diffuse intrinsic pontine glioma and recurrent medulloblastoma; $1.8 million over four years
Massachusetts General Hospital (Boston, Massachusetts); Amy Dickey; Phase 2 study of oral cimetidine for the treatment of protoporphyrias; $1.6 million over four years
Mayo Clinic Rochester (Rochester, Minnesota); Sani Kizilbash; Phase 1 study of WSD0922-FU for the treatment of high-grade astrocytoma; $1 million over three years
Mayo Clinic Rochester (Rochester, Minnesota); Wolfgang Singer; Phase 2 study of intrathecally administered autologous mesenchymal stem cells for the treatment of multiple system atrophy; $3.2 million over four years
Reveragen Biopharma, Inc.; Eric Hoffman; Phase 2a study of vamorolone for the treatment of becker muscular dystrophy; $1.2 million over two years
University of Florida (Gainesville, Florida); Peter Stacpoole; Phase 2A trial of dichloroacetate for the treatment of glioblastoma multiforme; $2.5 million over four years
As challenges and increased costs continued this year for clinical trials due to the COVID-19 pandemic, the FDA remains committed to supporting rare disease research by providing existing grantees with additional funding.
These resources allow ongoing studies to implement necessary steps to allow their research to continue and assure the safety of study participants, maintain compliance with good clinical practice and minimize risks to trial integrity.”
October 14, 2021: The U.S. FDA is announcing an upcoming meeting of its Antimicrobial Drugs Advisory Committee (AMDAC) to discuss Merck and Ridgeback’s request for an emergency use authorization (EUA) for molnupiravir, an investigational antiviral drug to treat COVID-19.
On Nov. 30, the advisory committee will meet to discuss the available data supporting the use of molnupiravir to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults who have tested positive for COVID-19, and who are at high risk for progression to severe COVID-19, including hospitalization or death.
“The FDA is evaluating the safety and effectiveness data submitted by Merck and Ridgeback in their emergency use authorization request for molnupiravir, a new oral treatment for high-risk individuals with a newly diagnosed COVID-19 infection.
We believe that, in this instance, a public discussion of these data with the agency’s advisory committee will help ensure clear understanding of the scientific data and information that the FDA is evaluating to make a decision about whether to authorize this treatment for emergency use,” said Patrizia Cavazzoni, M.D., director of the FDA’s Center for Drug Evaluation and Research.
At the FDA’s discretion, the agency may convene an advisory committee to solicit advice from independent outside experts on various complex scientific, technical, and policy issues.
The FDA does not always convene an advisory committee meeting in connection with EUA reviews, but may do so under certain circumstances when discussion with the advisory committee will help inform agency decision making.
The meeting was scheduled as soon as possible following the submission of the EUA request by the company.
This timeline allows for the FDA to thoroughly evaluate the data and information submitted in the EUA request before the meeting and to be prepared for a robust public discussion with the advisory committee members.
During the meeting, the committee will hear presentations from the company regarding the data for the antiviral drug. The FDA will also present its perspective regarding the sponsor’s data.
There will be an open public hearing during which the public will be given an opportunity to provide comments.
The FDA intends to make background materials for the AMDAC meeting available to the public, including the meeting agenda and committee roster, no later than two business days before the meeting.”
October 13, 2021: “Merck, known as MSD outside the United States and Canada, announced that the U.S.FDA has approved KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1)as determined by an FDA-approved test.
The approval is based on the Phase 3 KEYNOTE-826 trial evaluating KEYTRUDA plus chemotherapy (paclitaxel plus cisplatin or paclitaxel plus carboplatin), with or without bevacizumab, compared to the same chemotherapy regimens, with or without bevacizumab.
In this patient population, KEYTRUDA plus chemotherapy, with or without bevacizumab, demonstrated superior overall survival (OS; HR=0.64 [95% CI, 0.50-0.81]; p=0.0001) and progression-free survival (PFS; HR=0.62 [95% CI, 0.50-0.77]; p<0.0001) compared to chemotherapy, with or without bevacizumab, in patients whose tumors express PD-L1 (CPS ≥1).
Additionally, more patients responded to KEYTRUDA plus chemotherapy, with or without bevacizumab, than to chemotherapy, with or without bevacizumab, with an objective response rate (ORR) of 68% (95% CI, 62-74) versus 50% (95% CI, 44-56), respectively.
Among patients who responded, the median duration of response (DOR) was 18.0 months (range, 1.3+ to 24.2+) for KEYTRUDA plus chemotherapy, with or without bevacizumab, and 10.4 months (range, 1.5+ to 22.0+) for chemotherapy, with or without bevacizumab.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously.
Immune-mediated adverse reactions can occur at any time during or after treatment with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation.
Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.
Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of KEYTRUDA.
Based on the severity of the adverse reaction, KEYTRUDA should be withheld or permanently discontinued and corticosteroids administered if appropriate.
KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see “Selected Important Safety Information” below.
“Cervical cancer more commonly affects younger women and certain women of color in the U.S., and unfortunately, women diagnosed with persistent, recurrent or metastatic cervical cancer often have a low survival rate,” said Dr. Bradley Monk, oncologist with Arizona Oncology, medical director of U.S. Oncology Research Gynecology Program and professor of obstetrics and gynecology at University of Arizona’s College of Medicine and Creighton University School of Medicine.
“There have been no first-line approvals for women with persistent, recurrent or metastatic cervical cancer in the past seven years. I am excited for today’s approval of a new combination with KEYTRUDA, which offers a new treatment option for appropriate patients.”
“Today’s news is a meaningful step forward, as it offers a new therapeutic option for these patients and reinforces the role of KEYTRUDA in treating certain types of cervical cancers, with a second indication for the disease,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.
“The data showing a 36% reduction in the risk of death are compelling, and this approval brings an important new first-line treatment option to women with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1).”
Additionally, the FDA converted the accelerated approval of KEYTRUDA as a single agent for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1), as determined by an FDA-approved test, to a regular approval based on confirmatory data from KEYNOTE-826.
This approval was originally granted in June 2018 based on results from the KEYNOTE-158 trial.
Merck is committed to delivering meaningful advances in women’s cancers.
The company is rapidly expanding its extensive clinical development program for KEYTRUDA and several other investigational and approved medicines across gynecologic cancers, including researching KEYTRUDA for the treatment of other types of cervical cancer.
About KEYNOTE-826
The approval was based on data from KEYNOTE-826 (ClinicalTrials.gov, NCT03635567), a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial that enrolled 617 patients with persistent, recurrent or first-line metastatic cervical cancer who had not been treated with chemotherapy except when used concurrently as a radio-sensitizing agent.
Patients were enrolled regardless of tumor PD-L1 expression status. Patients with autoimmune disease that required systemic therapy within two years of treatment or a medical condition that required immunosuppression were ineligible.
Randomization was stratified by metastatic status at initial diagnosis, investigator decision to use bevacizumab and PD-L1 status (CPS <1 vs. CPS 1 to <10 vs. CPS ≥10). Patients were randomized (1:1) to one of the two treatment groups.
Patients in the KEYTRUDA arm received KEYTRUDA 200 mg intravenously every three weeks (Q3W) plus investigator’s choice of paclitaxel plus cisplatin or paclitaxel plus carboplatin Q3W, with or without bevacizumab Q3W.
Patients in the placebo arm received placebo plus investigator’s choice of paclitaxel plus cisplatin or paclitaxel plus carboplatin Q3W, with or without bevacizumab Q3W. All study treatments were administered on Day 1 of each 3-week treatment cycle.
Cisplatin could be administered on Day 2 of each three-week treatment cycle. Treatment with KEYTRUDA continued until RECIST v1.1-defined progression of disease, unacceptable toxicity or a maximum of 24 months.
Administration of KEYTRUDA was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator.
Assessment of tumor status was performed every nine weeks for the first year, followed by every twelve weeks thereafter.
The main efficacy outcome measures were OS and PFS as assessed by investigator review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ.
Additional efficacy outcome measures were ORR and DOR, according to RECIST v1.1, as assessed by investigator review.
Of the 617 enrolled patients, 548 patients (89%) had tumors expressing PD-L1 with a CPS ≥1.
Among these 548 enrolled patients with tumors expressing PD-L1, 273 patients were randomized to KEYTRUDA in combination with chemotherapy, with or without bevacizumab, and 275 patients were randomized to placebo in combination with chemotherapy, with or without bevacizumab.
Sixty-three percent of the 548 patients received bevacizumab as part of study treatment.
At study entry, 21% of patients had metastatic disease only, and 79% had persistent or recurrent disease, with or without distant metastases, of whom 39% had received prior chemoradiation only, and 17% had received prior chemoradiation plus surgery.
The key efficacy results for patients with tumors expressing PD-L1 (CPS ≥1) are summarized below:
Endpoint
KEYTRUDA +Chemotherapy* With orWithout Bevacizumabn=273
Placebo + Chemotherapy*With or WithoutBevacizumabn=275
OS
Number of patients with event (%)
118 (43.2)
154 (56.0)
Median in months (95% CI)
NR (19.8, NR)
16.3 (14.5, 19.4)
Hazard ratio† (95% CI)
0.64 (0.50, 0.81)
p-Value‡
0.0001
PFS
Number of patients with event (%)
157 (57.5)
198 (72.0)
Median in months (95% CI)
10.4 (9.7, 12.3)
8.2 (6.3, 8.5)
Hazard ratio† (95% CI)
0.62 (0.50, 0.77)
p-Value§
<0.0001
ORR
ORR(95% CI)
68% (62, 74)
50% (44, 56)
Complete response rate
23%
13%
Partial response rate
45%
37%
DOR
Median in months (range)
18.0 (1.3+, 24.2+)
10.4 (1.5+, 22.0+)
* Chemotherapy (paclitaxel and cisplatin or paclitaxel and carboplatin)† Based on the stratified Cox proportional hazard model‡ p-Value (one-sided) is compared with the allocated alpha of 0.0055 for this interim analysis (with 72% of the planned number of events for final analysis)§ p-Value (one-sided) is compared with the allocated alpha of 0.0014 for this interim analysis (with 82% of the planned number of events for final analysis)Response: Best objective response as confirmed complete response or partial response+ Denotes ongoing responseNR = not reached
Select Safety Profile From KEYNOTE-826
Fatal adverse reactions occurred in 4.6% of patients receiving KEYTRUDA plus chemotherapy, with or without bevacizumab, including three cases of hemorrhage, two cases of sepsis, two cases due to unknown causes and one case each of acute myocardial infarction, autoimmune encephalitis, cardiac arrest, cerebrovascular accident, femur fracture with perioperative pulmonary embolus, intestinal perforation and pelvic infection.
Serious adverse reactions occurred in 50% of patients receiving KEYTRUDA plus chemotherapy, with or without bevacizumab. Serious adverse reactions in ≥3% of patients included febrile neutropenia (6.8%), urinary tract infection (5.2%), anemia (4.6%), and acute kidney injury and sepsis (3.3% each).
KEYTRUDA was discontinued for adverse reactions in 15% of patients. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA (≥1%) was colitis (1%).
Adverse reactions leading to interruption of KEYTRUDA occurred in 66% of patients; the most common adverse reactions or laboratory abnormalities leading to interruption of KEYTRUDA (≥2%) were thrombocytopenia (15%), neutropenia (14%), anemia (11%), increased alanine aminotransferase (ALT) (6%), leukopenia (5%), fatigue/asthenia (4.2%), urinary tract infection (3.6%), increased aspartate aminotransferase (AST) and pyrexia (3.3% each), diarrhea, acute kidney injury and increased blood creatinine (2.6% each), colitis (2.3%), and decreased appetite and cough (2% each).
For patients treated with KEYTRUDA plus chemotherapy with bevacizumab (n=196), the most common adverse reactions (≥20%) were peripheral neuropathy (62%), alopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia (41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each), constipation and arthralgia (31% each), vomiting (30%), urinary tract infection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%) and decreased appetite (21%).
The most common adverse reactions (all grades ≥20%) for KEYTRUDA plus chemotherapy, with or without bevacizumab (n=307), were peripheral neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%), diarrhea (36%), constipation (28%), arthralgia (27%), vomiting (26%), hypertension and urinary tract infection (24% each), and rash (22%).
About Cervical Cancer
Cervical cancer forms in the cells lining the cervix, which is the lower part of the uterus.
While screenings and prevention have resulted in declining cervical cancer rates, the disease continues to affect many people in the U.S. and around the world. Cervical cancer is the fourth most commonly diagnosed cancer in women and the fourth leading cause of cancer-related death in women worldwide.
It is estimated there were more than 604,000 new cases of cervical cancer diagnosed and nearly 342,000 deaths resulting from the disease in 2020 globally. In the U.S., it is estimated there will be nearly 14,500 new cases of invasive cervical cancer diagnosed and almost 4,300 deaths resulting from the disease in 2021.
For patients in the U.S. who are diagnosed with cervical cancer, the five-year relative survival rate is 66.3%. For patients diagnosed with cervical cancer that has spread to distant parts of the body, this drops to 17.6%.
About KEYTRUDA® (pembrolizumab) Injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.
KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings.
The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.”
October 13, 2021: “Bristol Myers Squibb announced interim results from the Phase 3 open-label extension trial DAYBREAK, demonstrating the long-term efficacy and safety profile of Zeposia (ozanimod) in patients with relapsing forms of multiple sclerosis (MS).
These data (Presentation #P737) and five additional abstracts from company-sponsored studies will be presented at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place virtually October 13-15, 2021.
“Early and effective intervention can significantly impact physical and cognitive results over time, with low relapse rates an important indicator of patient outcomes,” said Bruce Cree, M.D., Ph.D., M.A.S., study investigator and Professor of Clinical Neurology, University of California San Francisco (UCSF) Weill Institute for Neurosciences and clinical research director, UCSF MS Center.
“These data from the DAYBREAK trial provide a clear picture of the long-term safety and efficacy profile of Zeposia, and reinforce its potential when used early in the treatment process for people living with relapsing forms of MS.”
In the DAYBREAK extension study, safety was consistent with prior findings and no new safety signals emerged during the reporting period with long-term use of Zeposia. Treatment with Zeposia demonstrated a low annualized relapse rate (ARR) of 0.103.
At months 36 and 48, 75% and 71% of participants were relapse-free and 3- and 6-month confirmed disability progression was observed in 13.9% and 11.4% of participants in the trial, respectively.
“Our presentations at ECTRIMS 2021 bolster the growing body of evidence underscoring the long-term efficacy and safety of Zeposia to treat relapsing forms of MS and demonstrate our focus on delivering meaningful innovations to help preserve the body and mind of people living with MS,” said Jonathan Sadeh, M.D., MSc., head of Immunology and Fibrosis Development, Bristol Myers Squibb. “We are committed to advancing our knowledge of this unpredictable, debilitating disease, with the goal of transforming medicine through science.”
In the DAYBREAK trial, of 2,494 participants exposed to Zeposia for an average of 46.8 months, 2,143 participants (85.9%) had any treatment-emergent adverse event (TEAE), 298 (11.9%) had a serious TEAE and 75 (3.0%) discontinued the study due to a TEAE.
The most common TEAEs were nasopharyngitis (19.6%), headache (15.8%), upper respiratory tract infection (11.1%) and lymphopenia (10.3%).
Data from this long-term observational study of patients treated for up to 62.7 months are consistent with the established safety profile of Zeposia and with sustained control of disease activity and disability progression.
At the ECTRIMS 2021 Congress, Bristol Myers Squibb and collaborators will present multiple abstracts that reinforce the company’s growing body of research in MS and commitment to people living with the disease.
Accepted abstracts are available on the ECTRIMS 2021 Congress website.
Visit this page on BMS.com for more information on Bristol Myers Squibb’s scientific approach and resources on MS.
Summary of Presentations:
Bristol Myers Squibb studies featured at the ECTRIMS 2021 Congress include:
Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: interim analysis of the DAYBREAK open-label extension study Author: Krzysztof W. Selmaj Presentation Number: P737 Presentation Topic: Long-term treatment monitoring
Hepatic safety of ozanimod in relapsing multiple sclerosis in the DAYBREAK open-label extension study Author: Krzysztof W. Selmaj Presentation Number: P725 Presentation Topic: Long-term treatment monitoring
Pharmacovigilance program for ozanimod, a recently approved treatment for relapsing forms of multiple sclerosis Author: Sonia Afsari Presentation Number: P156 Presentation Topic: Epidemiology
Effect of ozanimod on circulating leukocyte subtypes in patients with relapsing multiple sclerosis and comparison with healthy volunteers Author: Sarah Harris Presentation Number: P659 Presentation Topic: Immunomodulation/immunosuppression
Relationships between on-treatment changes in glial fibrillary acidic protein levels and clinical outcomes in patients with relapsing multiple sclerosis: post hoc analysis of the Phase 3 ozanimod SUNBEAM trial Author: Sarah Harris Presentation Number: P570 Presentation Topic: Fluid biomarkers
Treatment patterns in patients with multiple sclerosis: a single hospital cohort study in Sweden Author: Anna Castelo-Branco Presentation Number: P905 Presentation Topic: Others
About DAYBREAK
DAYBREAK is a Phase 3, multi-center, long-term open-label extension (OLE), randomized, double-blind, double-dummy, active-controlled, parallel group study to evaluate the safety and efficacy of Zeposia (ozanimod) administered orally to patients with relapsing forms of multiple sclerosis (MS).
Eligible patients from the RADIANCE, SUNBEAM and RPC01-1001 trials diagnosed with relapsing forms of MS are enrolled to receive treatment until the end of the DAYBREAK trial or until the development program is discontinued.
Patients in the trial are receiving Zeposia 0.92 mg (equivalent to ozanimod HCl 1 mg).
In total, 2,639 participants completed the parent clinical trials, and this interim analysis (data cutoff February 2021), includes a total of 2,494 participants with mean (range) Zeposia exposure of 46.8 (0.03–62.7) months in the OLE.
The primary objective of the trial is to evaluate safety in the overall population. Bristol Myers Squibb thanks the patients and investigators who are participating in this clinical trial.
About Multiple Sclerosis
Multiple sclerosis (MS) is a disabling, unpredictable disease in which the immune system attacks the protective myelin sheath that covers the nerves.
The myelin damage disrupts communication between the brain and the rest of the body.
Ultimately, the nerves themselves may deteriorate—a process that’s currently irreversible. MS affects 700,000 people in Europe and approximately 2.5 million people worldwide.
Relapsing forms of MS, including clinically isolated syndrome, relapsing remitting disease and active secondary progressive disease, is characterized by clearly defined attacks of worsening neurologic function.
These attacks—often called relapses, flare-ups or exacerbations—are followed by partial or complete recovery periods. During these recovery periods, also called remissions, symptoms improve partially or completely with no apparent progression of disease.
Since MS relapses are unpredictable, patients can feel frustrated, stressed, or scared when they occur.
Relapsing forms of MS are the most common disease course at the time of diagnosis. Approximately 85% of patients are initially diagnosed with relapsing forms of MS, compared with 10-15% with progressive forms of the disease.”
October 13, 2021: “A cornerstone of the U.S. FDA’s public health mission is to reduce the burden of chronic disease through improved nutrition.
As a nation, we are facing a growing epidemic of preventable, diet-related conditions like cardiovascular disease, diabetes and obesity, and the agency’s work in this area has become even more urgent.
For these reasons, we’re taking a critical step to further address preventable diet-related chronic diseases and advance health equity that we hope will become one of the most significant public health nutrition interventions in a generation.
Limiting certain nutrients, such as sodium, in our diets plays a crucial role in preventing diseases like hypertension and cardiovascular disease that disproportionately impact racial and ethnic minority groups; these diseases often result in hundreds of thousands of lives lost and billions in annual health care costs.
The ongoing COVID-19 pandemic has only amplified these health disparities and the need for improved nutrition, as people with cardiovascular disease and other underlying conditions are at increased risk for severe outcomes from COVID-19.
For these reasons, we’re taking a critical step to further address preventable diet-related chronic diseases and advance health equity that we hope will become one of the most significant public health nutrition interventions in a generation.
Today, the FDA is issuing a final guidance, “Voluntary Sodium Reduction Goals: Target Mean and Upper Bound Concentrations for Sodium in Commercially Processed, Packaged, and Prepared Foods,” which provides voluntary short-term sodium reduction targets for food manufacturers, chain restaurants and food service operators for 163 categories of processed, packaged and prepared foods.
The guidance is another step the agency is taking to advance the Administration’s whole-of-government approach to nutrition and health and improve future health outcomes.
By limiting certain nutrients like sodium in our diets, we can help prevent diseases like hypertension and cardiovascular disease that disproportionately impact racial and ethnic minority groups, often resulting in hundreds of thousands of lives lost and billions in annual health care costs.
The ongoing COVID-19 pandemic has only amplified these health disparities and the need for improved nutrition, as people with cardiovascular disease and other underlying conditions are at increased risk for severe outcomes from COVID-19.
Research shows that people consume 50% more sodium than recommended.
This includes our youngest and most vulnerable populations, with more than 95% of children aged 2 to 13 years old exceeding recommended limits of sodium for their age groups.
Although many consumers may want to reduce their sodium intake, about 70% of the sodium we eat comes from packaged, processed and restaurant foods, making it challenging to limit sodium.
Changes across the overall food supply will make it easier to access lower-sodium options and reduce intake even in the absence of behavior change.
The targets in the final guidance seek to decrease average sodium intake from approximately 3,400 milligrams (mg) to 3,000 mg per day, about a 12% reduction, over the next 2.5 years.
Although the average intake would still be above the Dietary Guidelines for Americans’ recommended limit of 2,300 mg per day for those 14 and older, we know that even these modest reductions made slowly over the next few years will substantially decrease diet-related diseases.
The final guidance outlines short-term goals that we’re recommending the food industry work to meet as soon as possible to help optimize public health.
We will continue our discussions with the food industry as we monitor the sodium content of the food supply to evaluate progress.
In the future, we plan to issue revised, subsequent targets to further lower the sodium content incrementally and continue to help reduce sodium intake.
This iterative approach will help support gradual reductions in sodium levels broadly across the food supply so that consumers’ tastes adjust, health outcomes improve and no one company or category of food is singled out or scrutinized.
Voluntary and gradual approaches such as this have also been successful in other countries, such as Canada and the U.K.
We first proposed recommendations for reducing sodium content in a 2016 draft guidance.
A number of companies in the food industry have already made changes to sodium content in their products, which is encouraging, but additional support across all types of foods to help consumers meet recommended sodium limits is needed.
Today, consumers can take steps to lower their sodium intake by reading food labels, including the Nutrition Facts label, asking for nutrition information at chain restaurants, choosing lower sodium options and speaking with their health care providers about eating healthier foods.
The FDA is committed to playing its part with the tools available to us to help create a healthier food supply, promote healthy habits early and empower consumers to make healthier food choices.
We have already taken steps through our Closer to Zero action plan for reducing exposure to toxic elements in foods commonly eaten by babies and young children to the lowest possible levels and have more work ahead using a similar iterative process.
Many of our federal, state and local partners also have initiatives underway that support sodium reduction and help people achieve healthier eating patterns overall. If we act together, we can have a profound impact on the health of millions of people.”
