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FDA and Mexican Counterparts Report Progress and Next Steps for Food Safety Partnership

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August 23, 2021: “As part of our ongoing efforts to ensure the safety of food imported from Mexico and advance protections for consumers in both countries, the U.S. FDA and its regulatory counterparts in Mexico – the Federal Commission for the Protection from Sanitary Risks External Link Disclaimer (Cofepris) and the National Service of Agro-Alimentary Health, Safety and Quality External Link Disclaimer (SENASICA) held the first Food Safety Partnership Annual Meeting on August 20, an important milestone in food safety. 

The meeting builds upon the Statement of Intent that was signed in September 2020 to enhance the partnership between all three agencies to work together on food safety in both countries.

A previous partnership, signed in 2014, focused on produce safety, while the current partnership has broadened the scope of products to include all human foods under the FDA’s jurisdiction that are traded between the two countries. 

During the meeting, the FDA, SENASICA and Cofepris reflected on accomplishments from the past year and set goals for the coming year of the partnership.

The FDA plans to work closely with SENASICA and Cofepris on activities that will enhance communication and oversight and enable us to share our experience with new approaches.

This kind of collaboration is critical because of the high volume of food trade across our border. About one-third of all imported food into the U.S. is from Mexico, including 60% of all imported produce.

As a result, the FDA, SENASICA and Cofepris work closely together on food establishment inspections and responding to foodborne illness outbreaks, as well as developing and implementing plans to enhance food safety in other areas of mutual public health interest.

The partnership aligns with the aims of the FDA’s New Era of Smarter Food Safety Blueprint through its core elements of tech-enabled traceability, smarter tools and approaches for prevention and outbreak response, new business models and food safety culture.

The FDA and its Mexican counterparts are working on four strategic priorities under the partnership: foodborne illness prevention (e.g., Salmonella in papaya and Cyclospora in produce), enhanced coordination for outbreak response, regulatory laboratory coordination (e.g., whole genome sequencing of foodborne bacteria, viruses and other pathogens) and food safety training opportunities for industry (e.g., produce safety and preventive controls for human foods). 

A key element of the New Era of Smarter Food Safety Blueprint is the use of smarter tools and approaches, especially for foodborne illness prevention and outbreak response.

The partnership is utilizing this approach by exchanging analytical methods to detect foodborne illness pathogens, such as Cyclospora.

The alignment of laboratory protocols can help to improve detection and reduce the risk of exposure to foodborne illness.

In addition, the partnership is increasing data sharing to improve outbreak response communications between the three agencies. The agencies are moving forward to update and refine the Binational Protocol (coordinated response) for outbreak response.

These modern approaches will ultimately help better protect public health on both sides of the border.

The partnership has also focused on ways to leverage SENASICA’s risk reduction standards and foster the development of industry best practices to further the safety of exported Mexican produce.

For example, since September 2020, through collaborative efforts with SENASICA and the Mexican papaya industry, more than 300 growers have been trained on the Produce Safety Alliance’s grower-training curricula and about 90% of the Mexican papaya industry has been trained on papaya best practices.

As part of a comprehensive effort to disseminate food safety training, the partnership will continue to strengthen work with industry on Foreign Supplier Verification Programs (FSVP) trainings for importers and the verification of papaya best practice implementation.

Over the last year and in the face of challenges associated with the global pandemic response, the partnership has continued to facilitate outreach and training in multiple languages on the FDA’s Produce Safety Rule (PSR) and FSVP rule for the produce industry. Working to keep consumers supplied with healthy, safe and nutritious food, SENASICA and Cofepris worked with the FDA to promote virtual webinars across Mexico.

The PSR is one of seven major rules established under the FDA Food Safety Modernization Act (FSMA) and includes requirements for produce that is grown domestically and imported or offered for import into the U.S. Next steps include assessing further outreach and training needs to enhance produce safety and traceability and supporting trainers to host additional grower trainings.

As the food supply becomes increasingly global, the FDA’s partnerships with our regulatory counterparts and food producers in other nations are more important than ever.

We look forward to our continued collaboration on food safety and hopefully in-person meetings and trainings in the coming year.”

https://www.fda.gov/news-events/press-announcements/fda-and-mexican-counterparts-report-progress-and-next-steps-food-safety-partnership

More than 700 million people with untreated hypertension

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August 25, 2021:

World Health Organization and Imperial College London joint press release

The number of adults aged 30–79 years with hypertension has increased from 650 million to 1.28 billion in the last thirty years, according to the first comprehensive global analysis of trends in hypertension prevalence, detection, treatment and control, led by Imperial College London and WHO, and published today in The Lancet. Nearly half these people did not know they had hypertension.

Hypertension significantly increases the risk of heart, brain and kidney diseases, and is one of the top causes of death and disease throughout the world.

It can be easily detected through measuring blood pressure, at home or in a health centre, and can often be treated effectively with medications that are low cost.

The study, conducted by a global network of physicians and researchers, covered the period 1990–2019.

It used blood pressure measurement and treatment data from over 100 million people aged 30–79 years in 184 countries, together covering 99% of the global population, which makes it the most comprehensive review of global trends in hypertension to date.

By analysing this massive amount of data, the researchers found that there was little change in the overall rate of hypertension in the world from 1990 to 2019, but the burden has shifted from wealthy nations to low- and middle-income countries.

The rate of hypertension has decreased in wealthy countries – which now typically have some of the lowest rates – but has increased in many low- or middle-income countries.

As a result, Canada, Peru and Switzerland had among the lowest prevalence of hypertension in the world in 2019, while some of the highest rates were seen in the Dominican Republic, Jamaica and Paraguay for women and Hungary, Paraguay and Poland for men. (See notes to editors for country breakdowns/rankings).

Although the percent of people who have hypertension has changed little since 1990, the number of people with hypertension doubled to 1.28 billion. This was primarily due to population growth and ageing.

In 2019, over one billion people with hypertension (82% of all people with hypertension in the world) lived in low- and middle-income countries.

Significant gaps in diagnosis and treatment

Although it is straightforward to diagnose hypertension and relatively easy to treat the condition with low-cost drugs, the study revealed significant gaps in diagnosis and treatment.

About 580 million people with hypertension (41% of women and 51% of men) were unaware of their condition because they were never diagnosed.  

The study also indicated that more than half of people (53% of women and 62% of men) with hypertension, or a total 720 million people, were not receiving the treatment that they need.

Blood pressure was controlled, which means medicines were effective in bringing blood pressure to normal ranges, in fewer than 1 in 4 women and 1 in 5 men with hypertension.

Professor Majid Ezzati, senior author of the study and Professor of Global Environmental Health at the School of Public Health at Imperial College London, said: “Nearly half a century after we started treating hypertension, which is easy to diagnose and treat with low-cost medicines, it is a public health failure that so many of the people with high blood pressure in the world are still not getting the treatment they need.”

Men and women in Canada, Iceland and the Republic of Korea were most likely to receive medication to effectively treat and control their hypertension, with more than 70% of those with hypertension receiving treatment in 2019.

Comparatively, men and women in sub-Saharan Africa, central, south and south-east Asia, and Pacific Island nations are the least likely to be receiving medication.

Treatment rates were below 25% for women, and 20% for men, in a number of countries in these regions, creating a massive global inequity in treatment.

Encouragingly, some middle-income countries have successfully scaled up treatment, and are now achieving better treatment and control rates than most high-income nations. For example, Costa Rica and Kazakhstan now have higher treatment rates than most higher-income countries.

Dr Bin Zhou, a research fellow at the School of Public Health at Imperial College London, who led the analysis, said: “Although hypertension treatment and control rates have improved in most countries since 1990, there has been little change in much of sub-Saharan Africa and Pacific Island nations.  

International funders and national governments need to prioritize global treatment equity for this major global health risk.”

New WHO guideline for hypertension treatment

The ‘WHO Guideline for the pharmacological treatment of hypertension in adults’, also released today, provides new recommendations to help countries improve the management of hypertension.

Dr Taskeen Khan, of WHO’s Department of Noncommunicable Diseases, who led the guideline development, said: “The new global guideline on the treatment of hypertension, the first in 20 years, provides the most current and relevant evidence-based guidance on the initiation of medicines for hypertension in adults.”

The recommendations cover the level of blood pressure to start medication, what type of medicine or combination of medicines to use, the target blood pressure level, and how often to have follow-up checks on blood pressure.

In addition, the guideline provides the basis for how physicians and other health workers can contribute to improving hypertension detection and management.

Dr Bente Mikkelsen, Director of WHO’s Department of Noncommunicable Diseases added: “The need to better manage hypertension cannot be exaggerated.

By following the recommendations in this new guideline, increasing and improving access to blood pressure medication, identifying and treating comorbidities such as diabetes and pre-existing heart disease, promoting healthier diets and regular physical activity, and more strictly controlling tobacco products, countries will be able to save lives and reduce public health expenditures.”

https://www.who.int/news/item/25-08-2021-more-than-700-million-people-with-untreated-hypertension

EU Approves RINVOQ® as First JAK Inhibitor for Atopic Dermatitis

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August 24, 2021: “AbbVie announced the EU approved RINVOQ® (upadacitinib), an oral, selective and reversible JAK inhibitor, for the treatment of moderate to severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy.

The recommended dose of RINVOQ for atopic dermatitis in adults is 15 mg or 30 mg once daily based on individual patient presentation, and 15 mg once daily for adolescents (12-17 years of age) and adults 65 years and older.

RINVOQ can be used with or without topical corticosteroids (TCS).

“This is a significant milestone for AbbVie in our pursuit to transform care in atopic dermatitis,” said Michael Severino, M.D., vice chairman and president, AbbVie.

“We are excited to provide an additional treatment option in Europe to help alleviate the burden of unrelenting itch and rash that many of these patients struggle with in daily life, despite available treatment options.”

The EC approval is supported by data from one of the largest registrational Phase 3 programs in atopic dermatitis with more than 2,500 adults and adolescents with moderate to severe disease.1 These studies evaluated the efficacy and safety of RINVOQ monotherapy (Measure Up 1 [MU1] and Measure Up 2 [MU2]) and with topical corticosteroids (AD Up [AU]) compared to placebo.1 In all three studies, the co-primary endpoints were at least a 75 percent improvement in the Eczema Area and Severity Index (EASI 75) and validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0/1 (clear or almost clear) at week 16.1

“As a dermatologist researching and treating atopic dermatitis for more than 25 years, I’ve seen first-hand the debilitating impact this disease can have on a person’s daily life,” said Alan Irvine, M.D., D.Sc., professor of dermatology, Trinity College Dublin, Ireland, and RINVOQ clinical study investigator.

“Clinicians need more tools to help them treat and manage this complex disease.

The degree and early onset of skin clearance and itch relief in the RINVOQ Phase 3 clinical studies are very encouraging. The outcomes have the potential to advance treatment goals for patients with moderate to severe atopic dermatitis.” 

Highlights From the Global Phase 3 Atopic Dermatitis Clinical Trial Program

Across the Phase 3 studies, all primary and secondary endpoints were met with 15 mg and 30 mg doses of RINVOQ compared to placebo. Highlights include:

  • Significantly more patients achieved EASI 75 at week 16 in the RINVOQ 15 mg group (MU1: 70%; MU2: 60%; AU: 65%) and the RINVOQ 30 mg group (MU1: 80%; MU2: 73%; AU: 77%), compared to placebo (MU1: 16%; MU2: 13%; AU: 26%).
  • Significantly more patients achieved vIGA-AD 0/1 at week 16 in the RINVOQ 15 mg group (MU1: 48%; MU2: 39%; 40: 31%) and the RINVOQ 30 mg group (MU1: 62%; MU2: 52%; AU: 59%) compared to placebo (MU1: 8%; MU2: 5%; AU: 11%).
  • Significantly more patients achieved clinically meaningful itch reduction (improvement in Worst Pruritus NRS ≥4) in the RINVOQ 15 mg group (MU1: 52%; MU2: 42%; AU: 52%) and the RINVOQ 30 mg group (MU1: 60%; MU2: 60%; AU: 64%) compared to placebo (MU1: 12%; MU2: 9%; AU: 15%) at week 16.
  • Clinically meaningful itch reduction (improvement in Worst Pruritus NRS ≥4) and skin clearance (EASI 75) were observed as early as week 1 and week 2, respectively, in patients treated with either dose of RINVOQ compared to those treated with placebo.
  • Results at week 16 continued to be maintained through week 52 in patients treated with either dose of RINVOQ.

The most commonly reported adverse reactions (≥5% of patients) with RINVOQ 15 mg or 30 mg were upper respiratory tract infection (25.4%), acne (15.1%), herpes simplex (8.4%), headache (6.3%) and increased blood creatine phosphokinase (CPK; 5.5%).The most common serious adverse reactions were serious infections (<1.0%).1

The Marketing Authorization means that RINVOQ is approved in all member states of the European Union, as well as Iceland, Liechtenstein, Norway and Northern Ireland.

RINVOQ is already approved for the treatment of moderate to severe atopic dermatitis in Russia, Saudi Arabia, United Arab Emirates, New Zealand and Chile, and is currently under review in the U.S. by the Food and Drug Administration (FDA).

*10,500 patients includes all patients across all arms (active treatment and placebo) in 8 Phase 3 trials in rheumatoid arthritis, 2 in psoriatic arthritis, 1 in ankylosing spondylitis and 5 in atopic dermatitis.

This includes 344 adolescent patients (aged 12 to 17 years) in the Phase 3 Measure Up 1, Measure Up 2 and, AD Up studies in atopic dermatitis.

Of the total number of patients included in these trials, 6,280 were randomized to receive RINVOQ at either dose.

About RINVOQ® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.

In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.

RINVOQ 15 mg is also approved by the U.S. Food and Drug Administration (FDA) for adults with moderately to severely active rheumatoid arthritis, and by the European Commission for adults with moderate to severe active rheumatoid arthritis, adults with active psoriatic arthritis (PsA) and adults with active ankylosing spondylitis (AS).

Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.”

https://news.abbvie.com/news/press-releases/european-commission-approves-rinvoq-upadacitinib-as-first-jak-inhibitor-in-european-union-for-treatment-both-adults-and-adolescents-with-moderate-to-severe-atopic-dermatitis.htm

Pfizer-BioNTech COVID-19 Vaccine COMIRNATY® wins Full FDA Approval

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August 23, 2021: “Pfizer Inc. and BioNTech SE announced that the U.S. Food and Drug Administration (FDA) approved the BLA for COMIRNATY® (COVID-19 Vaccine, mRNA) to prevent COVID-19 in individuals 16 years of age and older.

COMIRNATY is the first COVID-19 vaccine to be granted approval by the FDA.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210823005499/en/

The vaccine has been available in the U.S. under Emergency Use Authorization (EUA) since December 11, 2020 (as the Pfizer-BioNTech COVID-19 Vaccine).

The EUA permitted essential rollout of vaccine doses across the U.S. to help provide protection during the COVID-19 public health emergency, based on initial data from the pivotal Phase 3 clinical trial.

For FDA approval, Pfizer and BioNTech submitted a comprehensive data package that included longer-term follow-up data from the Phase 3 trial, where the vaccine’s high efficacy and favorable safety profile were observed up to six months after the second dose.

The BLA submission package also included the manufacturing and facilities data required for licensure.

Pfizer and BioNTech completed submission of the BLA in May 2021, and the BLA was granted Priority Review in July 2021.

“Based on the longer-term follow-up data that we submitted, today’s decision by the FDA affirms the efficacy and safety profile of our vaccine at a time when it is urgently needed.

About 60 percent of eligible Americans are fully vaccinated, and infection, hospitalization and death rates continue to rise rapidly among unvaccinated populations across the country,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer.

“I am hopeful this approval will help increase confidence in our vaccine, as vaccination remains the best tool we have to help protect lives and achieve herd immunity.

Hundreds of millions of doses of our vaccine already have been administered in the U.S. since December 2020, and we look forward to continuing to work with the U.S. government to reach more Americans now that we have FDA approval.”

“Today’s full approval by the FDA underlines the vaccine’s high efficacy and favorable safety profile,” said Ugur Sahin, M.D., CEO and Co-founder of BioNTech.

“Our companies have shipped more than one billion doses worldwide, and we will continue to work tirelessly to broaden the access to our vaccine and to be prepared for potential emerging escape variants.”

As announced on August 16, Pfizer and BioNTech plan to seek licensure of a third, or booster, dose of COMIRNATY in individuals 16 years of age and older via a supplemental BLA.

The companies also intend to submit a supplemental BLA to support potential full FDA approval of COMIRNATY in individuals 12 through 15 years of age once the required data out to six months after the second vaccine dose are available.

In the meantime, the vaccine remains available to 12- to 15-year-olds under the Emergency Use Authorization (EUA) granted by the FDA on May 10, 2021.

For individuals at least 12 years of age who have undergone solid organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise, a third dose of the vaccine also remains available under EUA following an amendment by the FDA on August 12.

COMIRNATY, which is based on BioNTech’s proprietary mRNA technology, was developed by both BioNTech and Pfizer.

BioNTech is the Marketing Authorization Holder in the United States, the European Union and the United Kingdom, and the holder of emergency use authorizations or equivalents in the United States (jointly with Pfizer), Canada and other countries.

Submissions to pursue regulatory approvals in those countries where emergency use authorizations or equivalent were initially granted are planned.

Indication & Authorized Use

COMIRNATY® (COVID-19 Vaccine, mRNA) is an FDA-approved COVID-19 vaccine made by Pfizer for BioNTech.

  • It is approved as a 2-dose series for prevention of COVID-19 in individuals 16 years of age and older
  • It is also authorized under Emergency Use Authorization (EUA) to be administered for emergency use to:
    • prevent COVID-19 in individuals 12 through 15 years, and
    • provide a third dose to individuals 12 years of age and older who have been determined to have certain kinds of immunocompromise

The Pfizer-BioNTech COVID-19 Vaccine has received EUA from FDA to:

  • prevent COVID-19 in individuals 12 years of age and older, and
  • provide a third dose to individuals 12 years of age and older who have been determined to have certain kinds of immunocompromise

The FDA-approved COMIRNATY® (COVID-19 Vaccine, mRNA) and the EUA-authorized Pfizer-BioNTech COVID-19 Vaccine have the same formulation and can be used interchangeably to provide the COVID-19 vaccination series. An individual may be offered either COMIRNATY® (COVID-19 Vaccine, mRNA) or the Pfizer-BioNTech COVID-19 Vaccine to prevent coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2.

EUA Statement

This emergency use of the product has not been approved or licensed by FDA, but has been authorized by FDA under an Emergency Use Authorization (EUA) to prevent Coronavirus Disease 2019 (COVID-19) for use in individuals 12 years of age and older; and the emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of the medical product under Section 564(b)(1) of the FD&C Act unless the declaration is terminated or authorization revoked sooner.

Important Safety Information

Individuals should not get the Pfizer-BioNTech COVID-19 Vaccine if they:

  • had a severe allergic reaction after a previous dose of this vaccine
  • had a severe allergic reaction to any ingredient of this vaccine

Individuals should tell the vaccination provider about all of their medical conditions, including if they:

  • have any allergies
  • have had myocarditis (inflammation of the heart muscle) or pericarditis (inflammation of the lining outside the heart)
  • have a fever
  • have a bleeding disorder or are on a blood thinner
  • are immunocompromised or are on a medicine that affects the immune system
  • are pregnant, plan to become pregnant, or are breastfeeding
  • have received another COVID-19 vaccine
  • have ever fainted in association with an injection

The vaccine may not protect everyone.

Side effects reported with the vaccine include:

  • There is a remote chance that the vaccine could cause a severe allergic reaction
    • A severe allergic reaction would usually occur within a few minutes to one hour after getting a dose of the vaccine. For this reason, vaccination providers may ask individuals to stay at the place where they received the vaccine for monitoring after vaccination
    • Signs of a severe allergic reaction can include difficulty breathing, swelling of the face and throat, a fast heartbeat, a bad rash all over the body, dizziness, and weakness
    • If an individual experiences a severe allergic reaction, they should call 9-1-1 or go to the nearest hospital
  • Myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining outside the heart) have occurred in some people who have received the vaccine. In most of these people, symptoms began within a few days following receipt of the second dose of the vaccine. The chance of having this occur is very low. Individuals should seek medical attention right away if they have any of the following symptoms after receiving the vaccine:
    • chest pain
    • shortness of breath
    • feelings of having a fast-beating, fluttering, or pounding heart
  • Side effects that have been reported with the vaccine include:
    • severe allergic reactions; non-severe allergic reactions such as rash, itching, hives, or swelling of the face; myocarditis (inflammation of the heart muscle); pericarditis (inflammation of the lining outside the heart); injection site pain; tiredness; headache; muscle pain; chills; joint pain; fever; injection site swelling; injection site redness; nausea; feeling unwell; swollen lymph nodes (lymphadenopathy); diarrhea; vomiting; arm pain
  • These may not be all the possible side effects of the vaccine. Serious and unexpected side effects may occur. The vaccine is still being studied in clinical trials. Call the vaccination provider or healthcare provider about bothersome side effects or side effects that do not go away

There is no information on the use of the vaccine with other vaccines.”

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-biontech-covid-19-vaccine-comirnatyr-receives-full

AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19

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 August 20,2021: “Positive high-level results from the PROVENT Phase III pre-exposure prophylaxis trial showed AstraZeneca’s AZD7442 achieved a statistically significant reduction in the incidence of symptomatic COVID-19, the trial’s primary endpoint.

AZD7442, a combination of two long-acting antibodies (LAAB), reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval (CI): 46, 90), compared to placebo.

The trial accrued 25 cases of symptomatic COVID-19 at the primary analysis.

There were no cases of severe COVID-19 or COVID-19-related deaths in those treated with AZD7442.

In the placebo arm, there were three cases of severe COVID-19, which included two deaths.

AZD7442 is the first antibody combination (non-vaccine) modified to potentially provide long-lasting protection that has demonstrated prevention of COVID-19 in a clinical trial.

The trial included 5,197 participants in a 2:1 randomisation AZD7442 to placebo. The primary analysis was based on 5,172 participants who did not have SARS-CoV-2 infection at baseline.

More than 75% of participants had co-morbidities, which include conditions that have been reported to cause a reduced immune response to vaccination.

The LAAB was well tolerated and preliminary analyses show adverse events were balanced between the placebo and AZD7442 groups.

Myron J. Levin, MD, Professor of Pediatrics and Medicine, University of Colorado School of Medicine, US, and principal investigator on the trial, said: “The PROVENT data show that one dose of AZD7442, delivered in a convenient intramuscular form, can quickly and effectively prevent symptomatic COVID-19.

With these exciting results, AZD7442 could be an important tool in our arsenal to help people who may need more than a vaccine to return to their normal lives.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “We need additional approaches for individuals who are not adequately protected by COVID-19 vaccines.

We are very encouraged by these efficacy and safety data in high-risk people, showing our long-acting antibody combination has the potential to protect from symptomatic and severe disease, alongside vaccines.

We look forward to sharing further data from the AZD7442 Phase III clinical trial programme later this year.”

AZD7442 was optimised using AstraZeneca’s proprietary YTE half-life extension technology, which could afford up to 12 months of protection from COVID-19, and is delivered by intramuscular injection.

Preliminary ‘in vitro’ findings from investigators at Oxford University and Columbia University demonstrate that AZD7442 neutralises recent emergent SARS-CoV-2 viral variants, including the Delta variant.1-6

AstraZeneca will prepare regulatory submission of the prophylaxis (PROVENT and STORM CHASER) data to health authorities for potential emergency use authorisation or conditional approval of AZD7442. Full results from PROVENT will be submitted for publication in a peer-reviewed medical journal and presented at a forthcoming medical meeting.

PROVENT
PROVENT is a Phase III, randomised, double-blind, placebo-controlled, multi-centre trial assessing the safety and efficacy of a single 300mg dose of AZD7442 compared to placebo for the prevention of COVID-19.

The trial was conducted in 87 sites in the US, UK, Spain, France and Belgium. 5,197 participants were randomised in a 2:1 ratio to receive a single intramuscular (IM) dose of either 300mg of AZD7442 (n = 3460) or saline placebo (n = 1,737), administered in two separate, sequential IM injections.

The primary efficacy endpoint was the first case of any SARS-CoV-2 RT-PCR positive symptomatic illness occurring post dose prior to day 183. Subjects will continue to be followed for 15 months.

Participants were adults 18 years-old and over who would benefit from prevention with the LAAB, defined as having increased risk for inadequate response to active immunisation (predicted poor responders to vaccines or intolerant of vaccine) or having increased risk for SARS-CoV-2 infection, including those whose locations or circumstances put them at appreciable risk of exposure to the SARS-CoV-2 virus.

Participants at the time of screening were unvaccinated and had a negative point-of-care SARS-CoV-2 serology test.

Approximately 43% of participants were 60 years and over.

In addition, more than 75% had baseline co-morbidities and other characteristics that are associated with an increased risk for severe COVID-19 should they become infected, including those with immunosuppressive disease or taking immunosuppressive medications, diabetes, severe obesity or cardiac disease, chronic obstructive pulmonary disease, chronic kidney and chronic liver disease.

Approximately 73% were White/Caucasian, 17% Black/African American, and 3% Asian. Approximately 15% of participants were Hispanic.

AZD7442
AZD7442 is a combination of two LAABs – tixagevimab (AZD8895) and cilgavimab (AZD1061) – derived from B-cells donated by convalescent patients after SARS-CoV-2 virus. Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein and were optimised by AstraZeneca with half-life extension and reduced Fc receptor and complement C1q binding.

The half-life extension more than triples the durability of its action compared to conventional antibodies and could afford up to 12 months of protection from COVID-19 following a single administration.

The reduced Fc receptor binding aims to minimise the risk of antibody-dependent enhancement of disease – a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.

AZD7442 is being studied in a comprehensive clinical trial programme for both prevention and treatment of COVID-19 in over 9,000 participants.

Ongoing trials include TACKLE COVID-19, a Phase III treatment trial in an outpatient setting and collaborator treatment trials in outpatient and hospitalised settings. AZD7442 is being assessed in both IM and intravenous administration routes.

AZD7442 is being developed with support from the US Government, including federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority in partnership with the Department of Defense; Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, under Contract No. W911QY-21-9-0001.

AstraZeneca is working with governments around the world to make AZD7442 accessible to high-risk populations as another valuable option in the fight to end COVID-19, should it prove to be effective and well tolerated.

Data published in Nature in July 2020 showed that in preclinical experiments, the LAABs were able to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease.

Under the terms of the licensing agreement with Vanderbilt, AstraZeneca will pay single-digit royalties on future net sales.”

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html

Novartis updates on BELINDA study for B-cell non-Hodgkin lymphoma

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Aug 24, 2021: “Novartis announced an update on the Phase III BELINDA study investigating Kymriah® (tisagenlecleucel) in aggressive B-cell non-Hodgkin lymphoma (NHL) after relapse or lack of response to first-line treatment.

The BELINDA study did not meet its primary endpoint of event-free survival compared to treatment with the standard-of-care (SOC).

SOC was salvage chemotherapy followed in responding patients by high-dose chemotherapy and stem cell transplant. The safety profile was consistent with the established safety profile of Kymriah.

Novartis will complete a full evaluation of the BELINDA data and work with investigators on the future presentation of the results.

“Patients with aggressive B-cell non-Hodgkin lymphoma who are refractory to first-line treatment are vulnerable and we are disappointed that the BELINDA study did not meet its primary endpoint in this setting,” said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development.

“Kymriah continues to demonstrate durable responses for patients with certain advanced blood cancers in the third-line setting.

We remain committed to accelerating development of Kymriah and our next-generation CAR-Ts and anticipate sharing early clinical results for these therapies at an upcoming medical meeting.”

“We were hopeful the BELINDA study would show that Kymriah could improve outcomes and the overall treatment experience for these patients in need. The study investigators will work together with Novartis in the coming weeks and months to understand the factors that contributed to this outcome,” said Michael R. Bishop, MD, Professor of Medicine and Director of the Hematopoietic Stem Cell Transplantation Program, University of Chicago Medicine and BELINDA Steering Committee Chair.

Novartis is grateful to the patients, families and investigators who participated in this trial for their determination to contribute to advancing the treatment of this aggressive blood cancer.

About the BELINDA study
The BELINDA study is a pivotal Phase III, randomized, open label, multicenter trial comparing two treatment strategies and assessing the efficacy, safety, and tolerability of Kymriah (tisagenlecleucel) compared to standard-of-care (SOC).

Patients in the trial had aggressive B-cell non-Hodgkin lymphoma with primary refractory disease, or which relapsed within 12 months of first-line treatment.

SOC was salvage chemotherapy followed in responding patients by high-dose chemotherapy and hematopoietic stem cell transplant (HSCT).

This international trial enrolled patients from over 73 sites in 18 countries worldwide.

The primary endpoint was event-free survival (EFS) defined as the time from the date of randomization to the date of the first documented disease progression or stable disease at or after the week 12 assessment, per blinded independent review committee (BIRC), or death at any time.

Secondary endpoints include EFS as assessed by local investigator, overall survival, overall response rate, duration of response, time to response and safety.

Patients in the control arm, receiving SOC, had the opportunity to cross over to receive Kymriah upon progression determined by BIRC.”

https://www.novartis.com/news/media-releases/novartis-provides-update-belinda-study-investigating-kymriah-second-line-treatment-aggressive-b-cell-non-hodgkin-lymphoma

Job Interview Questions for Clinical Data Management 2024

This blog is writing for 0-1 years of experienced individuals. Fresher’s and less experienced individuals should focus on basics of clinical research and clinical data management. Interviewers does not expect that freshers should know each and every thing about clinical data management. it is always expected that freshers should have a strong knowledge about basics of clinical research and clinical data management.

You can refer this blog to learn about basic of clinical research:

Please refer the below questions while preparing for CDM Job interviews. The Short answers are provided for each questions and links are provided if you want to explore it further.

What is eDC system?

It is a abbreviation of  electronic data capture and it is system/tool which is used to capture clinical trial data in electronic forms.

Explore our best Clinical Data Management Course

What are the different eDC systems?

There are many eDC system in the market such as Inform, RAVE, OC-RDC etc.

What do you understand by CRF?

As per ICH E6 (R2),

“A printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject”

In simple terms, we can say that it is the form (electronic/paper) which is used to capture the clinical data/information of patients as per the clinical trial protocol. It is a abbreviation of case report form. You can read in details here:
Basics of case report form

What are variables and fields:

Variable are the questions or data points present in the case report forms (CRF).
For example Patient age , country in demographics CRF are called variables. We are asking (question) about patient age and his country in the case report form, hence they are variable.
Fields are the places where site personals enter the data. for example in demography CRF, site has to enter patient age so adjacent to variable-age, there would be a blank space, where site can enter age.

If I need to give a real life example, then I would given an example of college admission form where your name and surnames questions are variables and that blank space where you write your name and surname are fields.

Basics of case report form

What is protocol?

It is clinical trial document which tells how to perform the trial, its purpose, drug being tested, method, statistical criteria, structure/design of the clinical trial, and visit schedules. It also focuses on wellbeing of participants and validity of clinical trial data.

Please note this is must know document for any fresher and experienced professionals.
Parts of a clinical trial protocol and Clinical Data Management (CDM) prospective to review
Clinical Trial Protocol

What is visit in clinical trial?

As per the protocol, participants have to come to  site/hospital to take  the  drug and/or for  assessments such as Lab, x ray etc, this is called as visit. It is properly defined in the visit schedule section of the protocol.

What do you know about CRC?

CRC or clinical research coordinators are the site personals who enters the clinical trial data in eDC and perform many activities on behalf of Principle investigator. They assist Principle investigator in many site activities as per protocol. Please note that ultimate responsibility goes to PI for performing the study at  site.
Beginner’s Guide to Clinical Research Coordinator

What do  you know about Auto queries and edit checks?

Whenever there is a discrepancy in the data entered in eCRF, a query (question) is fired by the eDC system asking more about data discrepancy. This is called auto query.

These auto queries are written by programmer on the input from data management or other line function such as safety etc. The programs firing auto queries are called edit checks.

Auto queries helps DM to know the discrepancy in the database. In general auto queries are directed towards site and site personals (CRC and PI) has to check auto queries and correct the data and/or reply to the auto queries. Based on corrected data and replies on auto queries, DM or other line function can close it or re-query it. Kindly refer the below link for details:
https://lifepronow.com/2020/07/11/free-course-on-clinical-data-management/

What is CDISC?

It is a abbreviation of Clinical Data Interchange Standards Consortium. It  is non for profit organization. It develops the standard for data  collection and reporting.

Please read more  about SDTM and ADAM  here.
ttps://www.cdisc.org/

What is serious adverse event?

As per FDA “An adverse event is any undesirable experience associated with the use of a medical product in a patient. The event is serious and should be reported to FDA when the patient outcome is:”

It  is considered serious  if it results in death, life threatening, Hospitalization (initial or prolonged), disability or  permanent damage and congenital anomaly/birth defect.”

https://www.fda.gov/safety/reporting-serious-problems-fda/what-serious-adverse-event

What do you understand by clinical data management?.

Clinical data  management deals  with clinical trial data and is responsible for data collection, data cleaning, maintaining its integrity, drafting of various clinical trial documents, collaboration across various  line function such as safety, medical, clinical, programming etc and final submission to statistical team for its analysis

  • What are various Phases of clinical data management?

Clinical data management activities can be divided into three parts:

Set up: In this activity, DM in collaboration with programming and other team, builds the CRFs into eDC as per protocol. DM has to perform testing of eDC to know if it functions as intended or not and draft many documents. Handling of third party data (external data)  is also finalised.

Conduct Phase: Once data base (eDC) is ready, site start entering the clinical data  and DM has to review the data  and raise queries if he/she observes any  discrepancies. Third party data and AE reconciliation is done here

Close out: In this phase, the clinical data is finally cleaned and data base is locked. All efforts are done to ensure that data is clean for submission to stats.

What is source data verification (SDV)?

site captures the clinical trial data on patient diaries or  similar documents and receive various lab reports on paper or different electronic format. All this clinical data needs to be transcribed into eDC by CRC and PI. The initial  documents (patient  diaries, lab reports) are  called source documents. Clinical research associate (CRA) verifies  the information of eDC to check whether information entered on eDC is same as captured on source document or not. This process is  called SDV.

Clinical Research Associate: Role, Responsibilities, Skills, and Salary

More experienced individuals can explore the below topics as well.

FDA Grants First of its Kind Indication for Chronic Sleep Disorder Treatment

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August 12, 2021: “The U.S. Food and Drug Administration approved a new indication for Xywav for idiopathic hypersomnia (IH) in adults.

IH is an uncommon chronic sleep disorder that causes people to be excessively sleepy during the day even after a good night’s sleep.

Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution is already approved for the treatment of cataplexy or excessive daytime sleepiness in patients seven years or older with narcolepsy.

“A novel indication for Xywav is significant as the FDA has never granted an approval for idiopathic hypersomnia,” said Eric Bastings, M.D., deputy director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research.

“Idiopathic hypersomnia is a life-long condition, and the approval of Xywav will be instrumental in providing treatment for symptoms such as excessive sleepiness and difficulty waking, and in effectively managing this debilitating disorder.”

The effectiveness of Xywav was evaluated in a double-blind placebo-controlled randomized-withdrawal study in 154 adult patients (ages 19 to 75 years) with IH.

In the clinical study, patients who were randomized to switch from Xywav to placebo experienced worsening on measures of sleepiness and symptoms of IH compared to patients randomized to continue treatment with Xywav.

In the clinical trial for IH, the most common adverse events as a result of the treatment observed in the study included nausea (21.4%), headache (16.2%), dizziness (11.7%), anxiety (10.4%) and vomiting (10.4%).

Xywav has a boxed warning for central nervous system depression and abuse and misuse.

The active moiety of Xywav is oxybate, also known as gamma-hydroxybutyrate (GHB), a Schedule I controlled substance. Abuse or misuse of illicit GHB has been associated with serious side effects including seizures, trouble breathing, changes in alertness, coma, and death.

Clinically significant respiratory depression and reduced level of alertness has occurred in adult patients taking sodium oxybate.

Because of the potential risks associated with Xywav, it is subject to strict safety controls on prescribing and dispensing under a program called a Risk Evaluation and Mitigation Strategy (REMS).

Specifically, under the Xywav REMS, it can be prescribed only by a certified prescriber, and dispensed only to an enrolled patient by a certified pharmacy.

Only a certified pharmacy that ships directly to patients can dispense Xywav. Xywav will not be available in retail pharmacies.

The FDA granted this application Fast Track and Priority Review designations. Xywav also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted the approval of Xywav to Jazz Pharmaceuticals plc.”

https://www.fda.gov/news-events/press-announcements/fda-grants-first-its-kind-indication-chronic-sleep-disorder-treatment

FDA Authorizes Additional Vaccine Dose for Certain Immunocompromised Individuals

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August 12, 2021: “The U.S. Food and Drug Administration amended the emergency use authorizations (EUAs) for both the Pfizer-BioNTech COVID-19 Vaccine and the Moderna COVID-19 Vaccine to allow for the use of an additional dose in certain immunocompromised individuals, specifically, solid organ transplant recipients or those who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices is scheduled to meet Friday to discuss further clinical recommendations regarding immunocompromised individuals.

Today’s action does not apply to people who are not immunocompromised.

“The country has entered yet another wave of the COVID-19 pandemic, and the FDA is especially cognizant that immunocompromised people are particularly at risk for severe disease.

After a thorough review of the available data, the FDA determined that this small, vulnerable group may benefit from a third dose of the Pfizer-BioNTech or Moderna Vaccines,” said Acting FDA Commissioner Janet Woodcock, M.D.

“Today’s action allows doctors to boost immunity in certain immunocompromised individuals who need extra protection from COVID-19.

As we’ve previously stated, other individuals who are fully vaccinated are adequately protected and do not need an additional dose of COVID-19 vaccine at this time.

The FDA is actively engaged in a science-based, rigorous process with our federal partners to consider whether an additional dose may be needed in the future.”

People who are immunocompromised in a manner similar to those who have undergone solid organ transplantation have a reduced ability to fight infections and other diseases, and they are especially vulnerable to infections, including COVID-19.

The FDA evaluated information on the use of a third dose of the Pfizer-BioNTech or Moderna Vaccines in these individuals and determined that the administration of third vaccine doses may increase protection in this population.

These patients should be counseled to maintain physical precautions to help prevent COVID-19.

In addition, close contacts of immunocompromised persons should get vaccinated, as appropriate for their health status, to provide increased protection to their loved ones.

It is recommended that immunocompromised individuals discuss monoclonal antibody treatment options with their health care provider should they contract or be exposed to COVID-19.

The FDA has authorized monoclonal antibody treatments for emergency use during this public health emergency for adults and pediatric patients (ages 12 and older weighing at least 40 kilograms or about 88 pounds) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization. 

One authorized product includes use for preventative (prophylaxis) treatment after being exposed to SARS-CoV-2; however, this product is not a substitute for vaccination. 

The Pfizer-BioNTech COVID-19 Vaccine is currently authorized for emergency use in individuals ages 12 and older, and the Moderna COVID-19 Vaccine is authorized for emergency use in individuals ages 18 and older.

Both vaccines are administered as a series of two shots: the Pfizer-BioNTech COVID-19 Vaccine is administered three weeks apart, and the Moderna COVID-19 Vaccine is administered one month apart.

The authorizations for these vaccines have been amended to allow for an additional, or third, dose to be administered at least 28 days following the two-dose regimen of the same vaccine to individuals 18 years of age or older (ages 12 or older for Pfizer-BioNTech) who have undergone solid organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise.

The EUA amendments for the Pfizer-BioNTech COVID-19 Vaccine and the Moderna COVID-19 Vaccine were issued to Pfizer Inc. and ModernaTX Inc., respectively.”

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised

Update on US regulatory review of AZ’s roxadustat in anaemia of chronic kidney disease

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August 11, 2021: “The US FDA has issued a complete response letter (CRL) regarding the New Drug Application (NDA) for roxadustat for the treatment of anaemia of chronic kidney disease (CKD), in both non-dialysis dependent (NDD) and dialysis-dependent (DD) adult patients.

The CRL requested an additional clinical trial on the safety of roxadustat in both the NDD and DD patient populations.

AstraZeneca is working with its partner FibroGen, Inc. (FibroGen) and the FDA to evaluate next steps.

The safety and efficacy of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, have been demonstrated in the Phase III programme including more than 8,000 patients and published in five peer-reviewed journal articles.

Roxadustat is approved in a number of countries, including China and Japan, for the treatment of anaemia in CKD in NDD and DD adult patients. It is under regulatory review in other jurisdictions, including in the European Union, where it has recently received a positive CHMP opinion.

Anaemia
Anaemia can be a serious medical condition in which patients have insufficient red blood cells (RBCs) and low levels of haemoglobin, a protein in RBCs that carries oxygen to cells throughout the body.

Anaemia of CKD frequently causes significant fatigue, cognitive dysfunction and decreased quality of life, and is associated with increased risk of hospitalisation, CV complications and death.

Severe anaemia is common in patients with CKD, cancer, myelodysplastic syndrome (MDS), inflammatory diseases and other serious illnesses. Anaemia is particularly prevalent in patients with CKD.

CKD affects 840 million patients worldwide and is generally progressive, characterised by gradual loss of kidney function that may eventually lead to kidney failure.

Phase III programme
The Phase III programme included more than 8,000 patients and was conducted by AstraZeneca, FibroGen and Astellas Pharma Inc. (Astellas).

The OLYMPUS, ALPS and ANDES trials evaluated roxadustat compared to placebo in NDD-CKD patients. ROCKIES, SIERRAS and HIMALAYAS evaluated roxadustat compared to epoetin alfa in DD-CKD and incident dialysis (ID) patients. 

HIMALAYAS evaluated roxadustat compared to epoetin alfa in ID patients; ROCKIES and SIERRAS included ID and prevalent dialysis patients.

Roxadustat
Roxadustat, an oral medicine, could be the first in a new class of treatments called oral HIF-PH inhibitors that promotes erythropoiesis, or RBC production, through increased endogenous production of erythropoietin, improved iron absorption and mobilisation, and reduction of hepcidin.

Roxadustat is also in clinical development for anaemia associated with MDS and for chemotherapy-induced anaemia.

Roxadustat is approved in China, Japan, Chile and South Korea (under the name Evrenzo), for the treatment of anaemia in CKD in NDD and DD adult patients.

In Europe, the Marketing Authorisation Application for Evrenzo for the treatment of anaemia in CKD in NDD and DD patients was submitted by Astellas and accepted by the European Medicines Agency for review in May 2020. It is under final regulatory review following a positive EU CHMP opinion in June 2021.

AstraZeneca and FibroGen are collaborating on the development and commercialisation of roxadustat for the potential treatment of anaemia in the US, China and other countries in the Americas, Australia and New Zealand, as well as Southeast Asia.

Astellas and FibroGen are collaborating on the development and commercialisation of roxadustat for the potential treatment of anaemia in Japan, Europe, Turkey, Russia and the Commonwealth of Independent States, the Middle East and South Africa.”

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/update-on-us-review-of-roxadustat.html

Santen and Sydnexis execute an exclusive licensing agreement for progressive childhood myopia

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August 10, 2021: “Santen SA, a specialist in ophthalmology, and Sydnexis Inc., a
biopharmaceutical company focused on the development of therapies for the treatment of progressive myopia, announce the signing of an exclusive licensing agreement for SYD-101, Sydnexis’ investigational proprietary low dose atropine formulation, for Europe, Middle East and Africa (EMEA).

SYD-101 is currently undergoing a large multicenter phase III clinical trial, the STAAR study, in Europe and the US.

If the study is successful and SYD-101 is thereafter approved, it will address the need for a medical product to help control myopia progression.

“Uncorrected myopia is the leading cause of distance vision impairment and it is children with early onset who are at greater risk of long-term eye complications,” says Dr Martina Brandner, Department of Ophthalmology, Medical University of Graz, Austria.

“At present, only the symptoms of myopia are corrected and so researching SYD-101 in the largest clinical study in this field is a critical step in finding a treatment to target the underlying disease.”

SYD-101 is an investigational low-dose atropine sulfate ophthalmic solution, 0.01% and 0.03%, designed to achieve efficacy, stability and reduce discomfort for improved treatment continuity.

While published reports have shown low concentrations of compounded atropine to be effective, these solutions are limited by a short shelf life and remain only stable if markedly acidified, which can also cause excessive burning and stinging in children.

Based on its unique and proprietary formulation, SYD-101 is an investigational low-dose atropine formulation designed to be pharmacologically stable without needing to
lower the pH in order to achieve a shelf life of up to three years at room temperature.”

https://www.santen.com/en/news/20210810.pdf

Enhertu improves progression-free survival in breast cancer trial

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August 09, 2021: “Positive high-level results from the head-to-head DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan), the AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) HER2-directed antibody drug conjugate (ADC), demonstrated superiority over trastuzumab emtansine (T-DM1).

At a planned interim analysis, the Independent Data Monitoring Committee (IDMC) concluded that DESTINY-Breast03 met the primary endpoint of progression-free survival (PFS) showing a highly statistically significant and clinically meaningful improvement for patients with HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

In DESTINY-Breast03, Enhertu also showed a strong trend toward improved overall survival (OS) compared to T-DM1 in a key secondary endpoint, although the OS data are still immature.

The safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified and no Grade 4 or 5 treatment-related interstitial lung disease events.

Susan Galbraith, Executive Vice President, Oncology R&D, said: “There is a continued need for new options and better outcomes for patients with HER2-positive metastatic breast cancer who often experience disease progression after initial treatment with available standards of care.

These transformative progression-free survival results demonstrate the superiority of Enhertu compared to T-DM1, and the encouraging safety data may open future opportunities to bring this benefit to patients in earlier treatment settings.”

Ken Takeshita, Global Head, Research and Development, Daiichi Sankyo, said: “DESTINY-Breast03 is the first global Phase III head-to-head trial of Enhertu against an active control and supports the potential of this medicineto become the new standard of care for patients with HER2-positive metastatic breast cancer following initial treatment with trastuzumab and a taxane.

We believe this highly sophisticated and specifically engineered ADC is fulfilling its promise to reshape the treatment of HER2-positive metastatic breast cancer, with the goal to move into earlier lines of treatment for HER2-positive breast cancer and many other HER2-expressing tumour types across our broad clinical trial programme.”

The data will be presented at an upcoming medical meeting and shared with health authorities.

Enhertu is approved for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting in the US, Japan, the EU and several other countries based on the results from the DESTINY-Breast01 trial.

Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.


Related News: Datopotamab deruxtecan and Enhertu show promising clinical activity in NSCL
Enhertu approved in EU for HER2-positive metastatic breast cancer

HER2-positive breast cancer
Breast cancer remains the most common cancer and is one of the leading causes of cancer-related deaths in women worldwide.

More than two million patients with breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.

Approximately one in five patients with breast cancer are considered HER2-positive.

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast, gastric, lung and colorectal cancers.

HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and a poor prognosis in breast cancer.

Despite initial treatment with trastuzumab and a taxane, patients with HER2-positive metastatic breast cancer will often experience disease progression.

More effective options are needed to further delay progression and extend survival.

The primary efficacy endpoint of DESTINY-Breast03 is PFS based on blinded independent central review.

DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised, open-label, registrational Phase III trial evaluating the safety and efficacy of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

Secondary efficacy endpoints include OS, objective response rate, duration of response, clinical benefit rate, PFS based on investigator assessment and safety.

DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. 

Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg)is approved in Canada, the EU, Israel, Japan, the UK and the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the results from the DESTINY-Breast01 trial.

Enhertu (6.4mg/kg) is also approved in Israel, Japan and the US for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Enhertu was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the “ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers,” based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC), based on the interim results of the HER2-mutated cohort of the DESTINY-Lung01 trial.

In May 2020, Enhertu also received Breakthrough Therapy Designation for the treatment of patients with metastatic NSCLC whose tumours have a HER2-mutation and with disease progression on or after platinum-based therapy.”

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/enhertu-head-to-head-trial-meets-primary-endpoint.html