CLINSQUARE: CLINICAL RESEARCH COURSES
Saturday, June 7, 2025
CLINSQUARE: Clinical Rsearch Courses by LIFEPRONOW
Home Blog Page 51

FDA approves Sanofi’s Nexviazyme® for late-onset Pompe disease

admin
-
0
FDA approves Sanofi’s Nexviazyme® for late-onset Pompe disease

August 06 2021: “The U.S. FDA has approved Nexviazyme® (avalglucosidase alfa-ngpt) for the treatment of patients one year of age and older with late-onset Pompe disease, a progressive and debilitating muscle disorder that impairs a person’s ability to move and breathe.

Nexviazyme is an enzyme replacement therapy (ERT) designed to specifically target the mannose-6-phosphate (M6P) receptor, the key pathway for cellular uptake of enzyme replacement therapy in Pompe disease.

Nexviazyme has been shown in clinical trials to provide patients with improvements in respiratory function and walking distance.

“Pompe disease is a debilitating and progressive condition that significantly inhibits mobility and breathing,” said Bill Sibold, Executive Vice President of Sanofi Genzyme.

“For decades, we’ve made it our responsibility to research how to target the M6P receptor, the key pathway for cellular uptake of enzyme replacement therapy.

Nexviazyme is a potential new standard of care for people living with late-onset Pompe disease and delivers on our promise to pursue medicines for patients living with rare diseases.”

Pompe disease affects an estimated 3,500 people in the United States and can present as infantile-onset Pompe disease (IOPD), the most severe form of Pompe disease with rapid onset in infancy, and late-onset Pompe disease (LOPD), which progressively damages muscles over time.

LOPD symptoms may present at any age. However, due to the wide spectrum of clinical presentations and progressive nature of the disease, it can take seven to nine years before patients receive an accurate diagnosis.

As the disease progresses, people with LOPD may require mechanical ventilation to help with breathing or a wheelchair to assist with mobility.

Targeted delivery to clear glycogen in muscle cells

Pompe disease is caused by a genetic deficiency or dysfunction of the lysosomal enzyme acid alpha-glucosidase (GAA), which results in build-up of complex sugars (glycogen) in muscle cells throughout the body.

The accumulation of glycogen leads to irreversible damage to the muscles, including the diaphragm that supports respiratory function and skeletal muscles that affect mobility, functional endurance and breathing.
        
The key pathway to transport GAA enzyme into the lysosomes in the cell is through the M6P receptor.

Nexviazyme is specifically designed to target M6P to improve cellular enzyme uptake and enhance glycogen clearance in target tissues with an approximate 15-fold increase in M6P content compared to alglucosidase alfa, the comparator arm in the pivotal study.

Nexviazyme demonstrated improvements in pivotal study

Nexviazyme has demonstrated improvements for people living with late-onset Pompe disease.

In the pivotal Phase 3 trial (COMET), Nexviazyme showed improvements in respiratory function and walking distance measures in people with LOPD and established its safety profile.

“Nexviazyme is a new and exciting therapeutic option for people with late-onset Pompe disease,” said Mazen M. Dimachkie, MD, FAAN, FANA, Professor of Neurology, Chief of the Neuromuscular Division and Executive Vice Chair of the Department of Neurology at the University of Kansas Medical Center. 

“The Phase 3 study results showed meaningful improvements in respiratory function and walking distance, which are impactful in this serious condition.”

Results from the COMET study comparing Nexviazyme to alglucosidase alfa in LOPD included:

  • When compared to baseline, patients treated with Nexviazyme had a 2.9-point improvement (SE=0.9) in forced vital capacity (FVC) percent-predicted at Week 49, the study’s primary endpoint.

    Patients treated with Nexviazyme had a 2.4-point greater improvement in FVC percent-predicted compared to patients treated with alglucosidase alfa at Week 49 meeting the measurement of non-inferiority (p=0.0074; 95% CI, -0.13, 4.99).

    Statistical superiority of Nexviazyme over alglucosidase alfa was not achieved (p=0.06).
  • A key secondary endpoint in the trial measured functional endurance with the 6-minute walk test (6MWT). When compared to baseline, patients treated with Nexviazyme walked 32.2 meters farther (SE=9.9) at Week 49.

    Patients treated with Nexviazyme walked 30 meters farther (95% CI, 1.33, 58.69) than patients treated with alglucosidase alfa at Week 49. Per the hierarchy of the study protocol, formal statistical testing for all secondary endpoints was not conducted.
  • During the double-blind active-controlled period of 49 weeks, serious adverse reactions were reported in two (2%) patients treated with Nexviazyme and in three (6%) patients treated with alglucosidase alfa.

    The most frequently reported adverse reactions (>5%) in Nexviazyme-treated patients were headache, pruritus (itching sensation), nausea, hives and fatigue.
  • Infusion associated reactions were reported in 13 (25%) of the Nexviazyme-treated patients and in 16 (33%) of patients treated with alglucosidase alfa.

    Infusion associated reactions reported in more than one patient on Nexviazyme were mild to moderate and included headache, diarrhea, itching, hives, and rash.
    None of the infusion associated reactions were severe.

Nexviazyme, a new ERT for late-onset Pompe disease

Nexviazyme is administered as a monotherapy ERT every two weeks.

The recommended dose is based on body weight (20 mg/kg for LOPD patients ≥30 kg or 40 mg/kg for LOPD patients <30 kg) and is administered incrementally via intravenous infusion.

Nexviazyme is expected to be available in the U.S. in the coming weeks.”

https://www.sanofi.com/en/media-room/press-releases/2021/2021-08-06-17-42-21-2276588

Bayer strengthens drug discovery platform through acquisition of Vividion Therapeutics

admin
-
0
Bayer strengthens drug discovery platform through acquisition of Vividion Therapeutics

August 5, 2021: “Bayer announced the acquisition of Vividion Therapeutics, Inc. (Vividion), a US-headquartered biopharmaceutical company utilizing novel discovery technologies to unlock high value, traditionally undruggable targets with precision therapeutics.

Vividion’s platform is able to produce a variety of small molecule therapies across indications, with initial focus on targets relevant to oncology and immunology.

Vividion’s lead programs include multiple precision oncology targets and precision immunology targets, with ongoing efforts on a transcription factor NRF2 antagonist for the potential treatment of NRF2 mutant cancers, as well as NRF2 activators for various inflammatory diseases such as irritable bowel disease – among other pre-clinical programs.

Following closing of the acquisition, Bayer will own full rights to Vividion’s proprietary discovery platform, which comprises three integrated, synergistic components: a novel chemoproteomic screening technology, an integrated data portal, and a proprietary chemistry library.

The acquisition of Vividion strengthens Bayer’s small molecule capabilities and expands Bayer’s reach into new modalities. Under the terms of the agreement, Bayer will pay an upfront consideration of USD 1.5 billion and potential success-based milestone payments of up to USD 500 million.

“This acquisition is a cornerstone of our strategy to fuel our pipeline with breakthrough innovation,” said Stefan Oelrich, Member of the Board of Management, Bayer AG and President of the Bayer’s Pharmaceuticals Division.

“Vividion’s technology is the most advanced in the industry, and it has demonstrated its ability to identify drug candidates that can target challenging proteins.

Together with Bayer’s existing know-how, we will be able to develop first-in-class drug candidates, increasing the value of our pipeline. We want to provide innovative therapies for patients whose medical needs are not yet met by today’s treatment options.”

Identification of drug candidates for proteins that are considered undruggable is a great challenge in drug discovery.

Vividion’s chemoproteomic screening platform is able to identify previously unknown binding pockets on well-validated protein targets by screening chemical probes against the entire human proteome to assess selectivity.

This yields highly potent and selective compounds that provide a wide therapeutic window for a variety of areas of high-unmet medical need.

Vividion’s technology has already proven its applicability pre-clinically in oncology and immune-related diseases, and has the potential to expand into additional indications.

“Despite advances in genomics, structural biology and high-throughput screening, about 90% of disease-causing proteins cannot be targeted by current therapies due to the lack of a known addressable binding site.

Our proprietary chemoproteomic platform technology addresses the key limitations of conventional screening techniques and allows us to discover previously unknown, or cryptic, functional pockets on the surface of proteins and identify small molecules that selectively bind to those targets,” said Jeff Hatfield, Chief Executive Officer at Vividion.

“When combined with Bayer’s expertise in the development of small molecules to market and patient, an unparalleled position comes into existence to unlock undruggable targets and generate first-in-class novel compounds for the benefit of patients.”

To preserve its entrepreneurial culture as an essential pillar for nurturing successful innovation, Vividion will continue to operate as an independent organization on an arm’s length basis.

Vividion will remain accountable to advance its technology and portfolio while benefiting from the experience, infrastructure and reach of Bayer as a global pharmaceutical company.

Closing of the transaction is contingent on customary closing conditions, including receipt of the required regulatory approvals, and is expected to take place in Q3 2021.”

https://media.bayer.com/baynews/baynews.nsf/id/Bayer-strengthens-drug-discovery-platform-through-acquisition-of-Vividion-Therapeutics?Open&parent=news-overview-category-search-en&ccm=020

FDA Participates in New ‘Collaborative Communities’ to Address Emerging Challenges in Medical Devices

admin
-
0
FDA Participates in New ‘Collaborative Communities’ to Address Emerging Challenges in Medical Devices

August 04, 2021: “The U.S. FDA announced participation in several new collaborative communities aimed at addressing challenges in patient health care.

Collaborative communities are a continuing forum where private and public sector representatives of the community work together on medical device challenges to achieve common objectives and outcomes. 

“We’re pleased to announce the progress we’ve made with participation in collaborative communities.

These collaborations with diverse stakeholders are not only a strategic priority for the FDA’s Center for Devices and Radiological Health, they also provide much needed forums for deep discussion and solution-driven initiatives to tackle important issues within the medical device ecosystem,” said Jeff Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health.

“The insights and outcomes developed by these groups will have long-standing impacts on public health.”

The FDA currently participates in 12 collaborative communities, which are established, managed and controlled by external stakeholders.

Collectively these communities are charting paths to accelerate and address regulatory science and other knowledge gaps to aid in medical device review and oversight.

They may also impact the delivery of healthcare and change clinical care paradigms. 

The most recent collaborations focus on topics such as: medical device development and product quality; understanding of valvular heart disease; innovations in digital pathology; reducing rates of intended self-injury and suicidal acts by people with diabetes; and strategies to increase the awareness, understanding and participation of racial and ethnic minorities in the medical technology industry.

The FDA participates in these collaborative communities:

  • Collaborative Community on Ophthalmic Imaging 
  • National Evaluation System for health Technology Coordinating Center (NESTcc) Collaborative Community
  • Standardizing Laboratory Practices in Pharmacogenomics Initiative (STRIPE) Collaborative Community
  • International Liquid Biopsy Standardization Alliance (ILSA)
  • Xavier Artificial Intelligence (AI) World Consortium
  • Case for Quality Collaborative Community
  • Heart Valve Collaboratory (HVC)
  • Wound Care Collaborative Community
  • Pathology Innovation Collaborative Community (PICC)
  • REducing SuiCide Rates Amongst IndividUals with DiabEtes (RESCUE) Collaborative Community
  • MedTech Color Collaborative Community on Diversity and Inclusion in Medical Device Product Development and Clinical Research (MedTech Color Collaborative Community)
  • Digital Health Measurement Collaborative Community (DATAcc)

“The number of collaborative communities has continued to grow, showing that, amidst the backdrop of the COVID-19 pandemic, many remain dedicated to the idea that together, they can better achieve common outcomes, solve shared challenges and leverage collective opportunities to improve public health,” said Michelle Tarver, M.D., Ph.D., deputy director of the Office of Strategic Partnerships and Technology Innovation in the FDA’s Center for Devices and Radiological Health.

Collaborative communities are convened by interested stakeholders and may exist indefinitely, produce deliverables as needed and tackle challenges with broad impacts.

The FDA does not establish, lead or operate collaborative communities, nor are collaborative communities intended to advise the FDA.

Instead, the FDA may participate in the community in order to contribute its knowledge and perspective to discussions of public health challenges and solutions.

The FDA reached the goal set as part of CDRH’s 2018-2020 Strategic Priorities of participating in at least 10 new collaborative communities by December 31, 2020.”

https://www.fda.gov/news-events/press-announcements/fda-participates-new-collaborative-communities-address-emerging-challenges-medical-devices

Positive phase 3 results for Valneva’s chikungunya vaccine

admin
-
0
Positive phase 3 results for Valneva’s chikungunya vaccine

Aug 5, 2021: A phase 3 trial of Valneva’s chikungunya vaccine candidate has induced protection in 98.5% of participants, exceeding the level needed for the FDA to accept an application for review and cementing the biotech’s lead over Merck in the race to develop a product to prevent the viral disease. 

Valneva went into the clinical trial aiming to show a single dose of the vaccine, VLA1553, induced protection in at least 70% of participants, a threshold set with the FDA.

Of the 268 subjects tested, 264 had protective neutralizing antibody titers against the virus 28 days after receiving the vaccine, resulting in a protection rate of 98.5%. The rates were similar in elderly and younger participants. 

The safety analysis included 3,082 subjects.

Valneva said 1.6% of subjects reported severe adverse events, typically fever. Around half of the participants experienced milder adverse events, with more than 20% of subjects suffering headache, fatigue and muscle pain. 

Valneva is now on course to be the first company to win FDA approval for a chikungunya vaccine. Merck, which entered the race through the $366 million 

takeover of Themis, recently completed a phase 2 trial of its chikungunya vaccine candidate.

The study was suspended “due to a clinical stock recovery action” from December 2020 to the completion date in June—never hitting its original enrollment goal. 

Emergent BioSolutions is also in the race. In May, Emergent shared two-year persistence data from a phase 2 clinical trial of its vaccine candidate. Emergent plans to start a phase 3 study this year, putting it on the heels of Valneva but likely too far back to beat VLA1553 to market.  

The chikungunya race is about more than just first-mover advantage.

The FDA is expected to grant a priority review voucher to the first company to win approval for a chikungunya vaccine under a push to incentivize tropical disease R&D. Priority review vouchers now sell for around $100 million.

Once on the market, Valneva sees reasons to think VLA1553 will fare well even if competition arrives from Merck and Emergent.

In IPO paperwork filed earlier this year, Valneva said both rival vaccines “face limitations relative to VLA1553,” notably because they “are likely to require multiple shots to reach necessary effectiveness.”

https://www.fiercebiotech.com/biotech/valneva-racing-merck-for-a-prv-hits-goal-vaccine-phase-3

Moderna Receives FDA Fast Track Designation for Respiratory Syncytial Virus Vaccine

admin
-
0
Moderna Receives FDA Fast Track Designation for Respiratory Syncytial Virus Vaccine

August 3, 2021: “Moderna, a biotechnology company pioneering messenger RNA therapeutics and vaccines announced that the U.S.FDA has granted Fast Track designation for mRNA-1345, its investigational single-dose mRNA vaccine against respiratory syncytial virus (RSV) in adults older than 60 years of age.

“We are pursuing an mRNA RSV vaccine to protect the most vulnerable populations – young children and older adults,” said Stéphane Bancel, Chief Executive Officer of Moderna.

“We are studying mRNA-1345 in these populations in an ongoing clinical trial and we look forward to sharing data when available.

The Fast Track designation for older adults underscores the urgent need for a vaccine against RSV. With our investments in science and manufacturing, we have taken eleven infectious disease vaccines into human clinical trials.

We have accelerated research and development of our infectious disease therapeutic area and we will continue to advance our mRNA vaccines into new areas of high unmet need.”

Respiratory syncytial virus is a common respiratory virus that generally causes cold-like symptoms. In the United States and areas with similar climates, RSV infections occur primarily during fall, winter, and spring.

Most people recover in a week or two, but RSV can be serious, especially for infants and older adults.

RSV is the most common cause of bronchiolitis and pneumonia in children younger than one year of age in the United States and can result in pneumonia and respiratory distress in older adults.

According to the U.S. Centers for Disease Control and Prevention, in the United States, RSV leads each year, on average, to approximately 58,000 hospitalizations among children younger than five years old, 177,000 hospitalizations among adults 65 years and older and 14,000 deaths among adults 65 years and older.

There is no approved vaccine available today for RSV.

Fast Track is designed to facilitate the development and expedite the review of therapies and vaccines for serious conditions and that fill an unmet medical need.

Programs with Fast Track designation may benefit from early and frequent communication with the FDA, in addition to a rolling submission of the marketing application.

The Company previously received Fast Track designation for its COVID-19 vaccine candidate, Zika vaccine candidate (mRNA-1893), methylmalonic acidemia (MMA) (mRNA-3704) and propionic acidemia (PA) (mRNA-3927) programs.

The Phase 1 study of mRNA-1345 to evaluate the tolerability and reactogenicity of mRNA-1345 in younger adults, older adults and children is ongoing.

All four cohorts of younger adults (ages 18-49 years) are fully enrolled. Dosing in the older adult cohort (ages 65-79 years) is ongoing.

The age range of toddlers in this de-escalation Phase 1 study is 12-59 months.

The Company shared the first interim analysis of the Phase 1 study of mRNA-1345, through 1-month post-vaccination, of the younger adult cohorts at its annual Vaccines Day on April 14, 2021.

Results showed the vaccine candidate generated a geometric mean rise in neutralizing antibodies relative to baseline of at least 11-fold.

The Company also intends to evaluate the potential of combinations of mRNA-1345 with its vaccines against other respiratory pathogens in children and separately in older adults. Moderna owns worldwide commercial rights to mRNA-1345.

About mRNA-1345

mRNA-1345 is a vaccine against RSV encoding for a prefusion F glycoprotein, which elicits a superior neutralizing antibody response compared to the postfusion state.

RSV is the leading cause of respiratory illness in young children.

Older adults (65+) are at high risk for severe RSV infections. mRNA-1345 uses the same lipid nanoparticle (LNP) as Moderna’s authorized COVID-19 vaccine and contains optimized protein and codon sequences.”

https://investors.modernatx.com/news-releases/news-release-details/moderna-receives-fda-fast-track-designation-respiratory

Pfizer Announces Phase 2b/3 Trial Results of Ritlecitinib in Alopecia Areata

admin
-
0
Pfizer Announces Phase 2b/3 Trial Results of Ritlecitinib in Alopecia Areata

August 04, 2021: “Pfizer announced positive top-line results from the Phase 2b/3 ALLEGRO trial evaluating oral once-daily ritlecitinib in patients with alopecia areata, an autoimmune disease driven by an immune attack on the hair follicles that causes hair loss on the scalp and can also affect the face and body.

Ritlecitinib 50 mg and 30 mg achieved the primary efficacy endpoint of the study, namely the proportion of patients with less than or equal to 20 percent scalp hair loss after six months of treatment versus placebo.

“We are pleased by these positive results for ritlecitinib in patients with alopecia areata, a devastating and complex autoimmune disease for which there are currently no U.S. FDA or European Medicines Agency approved treatments,” said Michael Corbo, PhD, Chief Development Officer, Inflammation & Immunology, Pfizer Global Product Development.

“We look forward to bringing this potential new treatment option to patients living with alopecia areata as soon as possible.”

The Phase 2b/3 ALLEGRO trial met the primary efficacy endpoint of improving scalp hair regrowth.

All participants entered the study with at least 50 percent scalp hair loss due to alopecia areata, as measured by the Severity of Alopecia Tool (SALT) score.

A statistically significantly greater proportion of patients who took ritlecitinib 30 mg or 50 mg once-daily, with or without a four-week initial treatment of 200 mg once-daily, had 20 percent or less scalp hair loss (an absolute SALT score ≤20) after 24 weeks of treatment compared with placebo.

This was followed by a 24-week extension period, during which all participants initially randomized to receive ritlecitinib continued on the same regimen, while participants who received placebo during the initial 24 weeks advanced to one of two regimens: 200 mg for four weeks followed by 50 mg for 20 weeks, or 50 mg for 24 weeks.

The study also included a 10 mg dosing arm, which was assessed for dose-ranging and was not tested for statistically significant efficacy compared to placebo.

The safety profile seen with ritlecitinib was consistent with previous studies. Overall, the percentage of patients with adverse events (AEs), serious AEs and discontinuing due to AEs was similar across all treatment groups.

The most common AEs seen in the study were nasopharyngitis, headache and upper respiratory tract infection.

There were no major adverse cardiac events (MACE), deaths or opportunistic infections in the trial. Eight patients who were treated with ritlecitinib developed mild to moderate herpes zoster (shingles).

There was one case of pulmonary embolism in the ritlecitinib 50 mg group, which was reported to have occurred on Day 169.

There were two malignancies (both breast cancers) reported in the ritlecitinib 50 mg group, which were reported to have occurred on Day 68 and Day 195. Both participants were discontinued from the study.

Full results from this study will be submitted for future scientific publication and presentation. These data, together with data that will become available from ALLEGRO-LT, will form the basis for planned future regulatory filings.

Ritlecitinib is the first in a new investigational class of covalent kinase inhibitors that have high selectivity for Janus kinase 3 (JAK3) and members of the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family.

In laboratory studies, ritlecitinib has been shown to block the activity of signaling molecules and immune cells believed to contribute to loss of hair in people with alopecia areata.

Ritlecitinib, which was granted Breakthrough Therapy designation from the U.S. FDA for the treatment of alopecia areata in September 2018, is also being evaluated for vitiligo, rheumatoid arthritis, Crohn’s disease and ulcerative colitis.

About the Phase 2b/3 ALLEGRO Trial

This randomized, placebo-controlled, double-blind study investigated ritlecitinib in patients 12 years of age and older with alopecia areata (n=718).

Patients included in the study had 50 percent or more hair loss of the scalp, including patients with alopecia totalis (complete scalp hair loss) and alopecia universalis (complete scalp, face and body hair loss), and were experiencing a current episode of alopecia areata that had lasted between six months and ten years.

Patients were randomized to receive ritlecitinib 50 mg or 30 mg (with or without one month of initial treatment with once-daily ritlecitinib 200 mg), ritlecitinib 10 mg or placebo.

The primary endpoint was the proportion of patients with scalp hair regrowth in response to ritlecitinib treatment, based on an absolute SALT Score ≤20 at Week 24. SALT is a tool that measures the amount of scalp hair loss.

The tool divides the scalp into standard regions, and each region contributes to the total SALT score, which ranges from 0 to 100.

A SALT score of 0 corresponds to no scalp hair loss, while a SALT score of 100 corresponds to a total lack of hair on the scalp.”

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-results-phase-2b3-trial

What is Dechallenge, Rechallenge and Prechallenge in Clinical trials?

admin
-
0
What is Dechallenge, Rechallenge and Prechallenge in Clinical trials?

“Challenge – Challenge refers to the giving of the drug to the patient during the AE or treatment in question. 

That is, a patient is started today on, say, ampicillin orally.  This is the “challenge”.

Dechallenge (DC) and Rechallenge (RC) terminology often used in clinical trial to determine action taken for medical product.

It specifically refers to suspect drug but not for event as whole.

Dechallenge : 

Dechallenge : This term is use when the suspect drug was discontinued or withdrawn or dose reduced due to adverse event (AE).

Dechallenge (DC) can be classified into

  1. Positive Dechallenge: When the suspect drug was stopped or withdrawn, or the dose was reduced, and the adverse event was improved or resolved.

For example, the AE (which could actually be an adverse reaction – AR) of diarrhoea went away a day after the patient stopped taking ampicillin.

  • Negative Dechallenge: When the suspect drug was discontinued or withdrawn, or the dose was reduced, but the adverse event did not improve or resolve. For instance, the diarrhoea persisted even after the ampicillin was discontinued.

It’s important to note that these can be a little confusing because a “positive” dechallenge refers to the problem disappearing.

  • Unknown: When suspect drug was discontinued or withdrawn or dose reduced but the result of dechallange was unknown.
  • Dechallenge not applicable: This term is used in the following situations: treatment for an adverse event, death, drug discontinuation prior to the AE, medication error, drug overdose, and drug exposure during pregnancy.

Rechallenge (RC):

Rechallenge (RC): This term is use when the suspect drug wasrestarted after dechallenge and it only applicable after positive dechallenge.

Rechallenge (RC) can be classified into:

  1. Positive Rechallenge: When the suspect drug was re-introduced and event reappeared.
  2. Negative Rechallenge: when the suspect drug re-introduced and event did not reappear.
  3. Unknown: when the suspect drug re-introduced but result of rechallange was unknown.
  4. Rechallenge not applicable: when the drug was not re-introduced.

Prechallenge:

Prechallenge: This is a relatively new term that refers to the use of the same drug in the past. For example, the patient may have taken Ampicillin for an infection two years ago. If the patient previously took the drug and no adverse events occurred, this argues against the drug causing the AE in the current instance.

Moreover, this has a number of flaws, including forgetting what happened if it happened years ago.

In the case of an allergic reaction, the first use “primes the pump,” so to speak, and the allergic reaction manifests itself only on subsequent uses. This is a flimsy concept.

So, the general principles around these concepts run as follows:

If a patient takes a drug and experiences an adverse effect (AE), the question is whether the AE is due to the drug (thus an AR or Adverse Drug Reaction ADR) or not.

Obviously, this is a critical point in determining the drug’s safety and whether or not it can or should be continued in the specific patient.

As the FDA has stated, it is typically difficult to determine causality in a single individual experiencing an AE.

However, we must do so in clinical trials as well as in post-marketing signalling cases. After the AE occurs, it is common for the physician to discontinue the drug to see if the AE resolves.

If it does disappear, this is a positive dechallenge and suggests that, at least in terms of the temporal aspects of the case, the drug may be the source of the AE.

If it does not disappear, it may be less likely that drug was the cause of the event, unless the drug caused an irreversible change that cannot be reversed (e.g. blindness).

If the AE disappears and the patient really needs the drug and there are no adequate substitutes, the doctor may consider restarting drug if the AE was not serious or severe (one would avoid restarting if the AE was, say, laryngospasm or ventricular tachycardia).

This is the rechallenge.

If the drug is used again and the same AE occurs, this is considered a positive rechallenge and is regarded by many as a fairly strong indicator of causality: the drug is a likely suspect cause of the AE.

If the AE does not reoccur, many people believe that the drug did not cause it, and causality is less likely.

Finally, a second dechallenge is possible. The same scenario as before.”

https://www.c3isolutions.com/blog/challenges-prechallenges-dechallenges-and-rechallenges/

https://www.yourdictionary.com/rechallenge

https://link.springer.com/article/10.1007/s40264-013-0023-0

CMA fines pharma firm over pricing of crucial thyroid drug

admin
-
0
CMA fines pharma firm over pricing of crucial thyroid drug

July 29, 2021: “The CMA has imposed over £100 million in fines after Advanz inflated the price of thyroid tablets, causing the NHS and patients to lose out.

  • Advanz increased the price of thyroid tablet packs from £20 in 2009 to £248 in 2017 – an increase of 1,110%.
  • Latest CMA fine “sends a clear message” to the pharma sector that breaking the law will not be tolerated.

Following an investigation, the Competition and Markets Authority (CMA) has found that from 2009 until 2017 the pharmaceutical company Advanz charged excessive and unfair prices for supplying liothyronine tablets which are used to treat thyroid hormone deficiency.

They achieved this because liothyronine tablets were among a number of drugs that, although genericised, faced limited or no competition and therefore could sustain repeated price increases.

This strategy, which began in 2007, involved an overall price increase for liothyronine tablets of more than 6,000%.

The CMA has fined the firms involved a total of over £100 million for the relevant periods in which they broke the law: Advanz (£40.9 million), together with HgCapital (£8.6 million) and Cinven (£51.9 million) – two private equity firms which were previously owners of the businesses now forming part of Advanz.

The price increases were not driven by any meaningful innovation or investment, volumes remained broadly stable, and the cost of producing the tablets did not increase significantly.

NHS spending on the tablets in 2006, the year before the implementation of the strategy, was £600,000, but by 2009 had increased to more than £2.3 million and jumped to more than £30 million by 2016.

Eventually the drug was placed on the NHS ‘drop list’ in July 2015. This led to patients being faced with the prospect of having their current treatment stopped or having to purchase liothyronine tablets at their own expense.

That is particularly concerning, given that many patients do not respond adequately to the main treatment for hypothyroidism, levothyroxine tablets – and instead rely on liothyronine tablets to alleviate symptoms such as extreme fatigue and depression.

Andrea Coscelli, Chief Executive of the CMA, said:

“Advanz’s decision to ratchet up the price of liothyronine tablets and impose excessive and unfair prices for over eight years came at a huge cost to the NHS, and ultimately to UK taxpayers.

But that wasn’t all – it also meant that people dealing with depression and extreme fatigue, as a result of their thyroid conditions, were told they could not continue to receive the most effective treatment for them due its increased price.

“Advanz’s strategy exploited a loophole enabling it to reap much higher profits.

This fine of over £100 million, and our work in the pharma sector to date, sends a clear message that breaking the law has serious consequences.”

As well as imposing substantial fines, the CMA’s decision makes it easier for the NHS to seek compensation for the firms’ behaviour, by way of damages, should it choose to do so.

The investigation into these firms is part of the CMA’s ongoing work in the pharmaceutical sector.

Recent action includes securing an £8 million repayment to the NHS after companies took part in illegal arrangements relating to the supply of fludrocortisone, and fining firms £260 million for competition law breaches in relation to the supply of hydrocortisone tablets.

A number of other CMA investigations are continuing.”

https://www.gov.uk/government/news/cma-fines-pharma-firm-over-pricing-of-crucial-thyroid-drug

Sanofi to acquire Translate Bio, boost its mRNA technology across vaccines

admin
-
0
Sanofi to acquire Translate Bio, boost its mRNA technology across vaccines

August 03 2021: “As part of Sanofi’s endeavor to accelerate the application of messenger RNA (mRNA) to develop therapeutics and vaccines, the company has entered into a definitive agreement with Translate Bio, a clinical-stage mRNA therapeutics company, under which Sanofi will acquire all outstanding shares of Translate Bio for $38.00 per share in cash, which represents a total equity value of approximately $3.2 billion (on a fully diluted basis).

The Sanofi and Translate Bio Boards of Directors unanimously approved the transaction.

“Translate Bio adds an mRNA technology platform and strong capabilities to our research, further advancing our ability to explore the promise of this technology to develop both best-in-class vaccines and therapeutics,” said Paul Hudson, Sanofi Chief Executive Officer. 

“A fully owned platform allows us to develop additional opportunities in the fast-evolving mRNA space.

We will also be able to accelerate our existing partnered programs already under development. Our goal is to unlock the potential of mRNA in other strategic areas such as immunology, oncology, and rare diseases in addition to vaccines.”

“Sanofi and Translate Bio have a shared commitment to innovation in the mRNA space.

With Sanofi’s long-standing expertise in developing and commercializing vaccines and other innovative medicines on a global scale, Translate Bio’s mRNA technology is now even better positioned to reach more people, faster,” said Ronald Renaud, Chief Executive Officer, Translate Bio. 

“The talented and dedicated Translate Bio team has built the foundation of a strong mRNA platform.

Our expertise coupled with that of Sanofi has driven significant progress under the collaboration thus far, and we believe that this acquisition will strengthen the team’s ability to achieve the full potential of the mRNA technology.”

In June 2018, Sanofi and Translate Bio entered into a collaboration and exclusive license agreement to develop mRNA vaccines which was further expanded in 2020 to broadly address current and future infectious diseases.

There are two ongoing mRNA vaccine clinical trials under the collaboration, the COVID-19 vaccine Phase 1/2 study with results expected in Q3 2021 and the mRNA seasonal influenza vaccine Phase 1 trial with results due in Q4 2021.

The acquisition builds on Sanofi’s establishment of a first-of-its kind vaccines mRNA Center of Excellence.

On the therapeutic side, Translate Bio has an early-stage pipeline in cystic fibrosis and other rare pulmonary diseases.

In addition, discovery work is ongoing in diseases that affect the liver, and Translate Bio’s MRTTM platform may be applied to various classes of treatments, such as therapeutic antibodies or vaccines in areas such as oncology.

Sanofi’s recent acquisition of Tidal Therapeutics expanded the company’s mRNA research capabilities in both immuno-oncology and inflammatory diseases.

The Translate Bio acquisition further accelerates Sanofi’s efforts to develop transformative medicines using mRNA technology.

Transaction Terms

Under the terms of the merger agreement, Sanofi will commence a cash tender offer to acquire all outstanding shares of Translate Bio common stock for $38.00 per share in cash reflecting a total equity value of Translate Bio of approximately $3.2 billion.

The purchase price represents a premium of 56% to Translate Bio’s volume-weighted average price per share over the past 60 days.

To demonstrate their commitment to the transaction, the chief executive officer of Translate Bio and Translate Bio’s largest shareholder, The Baupost Group, L.L.C., have signed binding commitments to support the tender offer.

These binding commitments, combined with the Translate Bio shares already owned by Sanofi or its affiliates, represent a total of approximately 30% of Translate Bio’s total shares outstanding.

The consummation of the tender offer is subject to customary closing conditions, including the tender of a number of shares of Translate Bio common stock that together with shares already owned by Sanofi or its affiliates represents at least a majority of the outstanding shares of Translate Bio common stock, the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, and other customary conditions.

Following the successful completion of the tender offer, a wholly owned subsidiary of Sanofi will merge with Translate Bio and the outstanding Translate Bio shares not already owned by Sanofi or its affiliates that are not tendered in the tender offer will be converted into the right to receive the same $38.00 per share in cash paid in the tender offer.

The tender offer is expected to commence later this month. Sanofi plans to fund the transaction with available cash resources.

Subject to the satisfaction or waiver of customary closing conditions, Sanofi expects to complete the acquisition in the third quarter of 2021.

Morgan Stanley & Co. International plc is acting as exclusive financial advisor to Sanofi while Weil, Gotshal & Manges LLP is acting as legal counsel.

Centerview Partners is acting as lead financial advisor to Translate Bio in the transaction, while Paul, Weiss, Rifkind, Wharton & Garrison LLP is acting as legal counsel.

Evercore is also acting as a financial advisor in this transaction to Translate Bio. MTS Health Partners, LP is also giving financial advice to Translate Bio.”

https://www.sanofi.com/en/media-room/press-releases/2021/2021-08-03-07-00-00-2273307

BMS Statement on Istodax® for Relapsed Peripheral T-cell Lymphoma

admin
-
0
BMS Statement on Istodax® for Relapsed Peripheral T-cell Lymphoma

July 02, 2021: “In 2011, Celgene Corporation, now a wholly owned subsidiary of Bristol Myers Squibb, received accelerated approval by the U.S. FDA for Istodax® (romidepsin), a histone deacetylase (HDAC) inhibitor, as monotherapy for the treatment of peripheral T-cell lymphoma (PTCL) in adult patients who have received at least one prior therapy.

This accelerated approval was based upon results from two clinical studies, assessing the effect of Istodax on the surrogate endpoint of overall response rate.

Bristol Myers Squibb conducted a subsequent confirmatory Phase 3 study evaluating romidepsin plus CHOP (Ro-CHOP) versus CHOP in first-line PTCL patients, but the trial did not meet the primary efficacy endpoint of progression free survival. 

Based on this outcome, Bristol Myers Squibb made the decision to withdraw the PTCL indication from the U.S. market.

The company took this action in accordance with the FDA’s requirements for evaluating accelerated approvals that have not demonstrated sufficient clinical benefit.

Bristol Myers Squibb is notifying healthcare professionals about the withdrawal. 

Istodax remains on the market for treatment of patients with cutaneous T-cell lymphoma (CTCL) who have received at least one prior systemic therapy.

Patients who are being treated with Istodax for PTCL should consult with their healthcare provider in all aspects of their medical care and may remain on treatment if deemed clinically appropriate by the treating physician. 

“While the outcome of the confirmatory study in peripheral T-cell lymphoma is disappointing, Bristol Myers Squibb will continue to provide Istodax for patients with cutaneous T-cell lymphoma, where it remains an approved and important treatment option,” said Noah Berkowitz, M.D., Ph.D., senior vice president, Hematology Development, Bristol Myers Squibb. 

“As always, our efforts across blood cancer research and development remain centered on delivering better outcomes for patients in need.”

Since the initial approval of Istodax, nearly a decade ago, more options have been made available for patients, many of which have redefined treatment across PTCL and other hematologic conditions.

Bristol Myers Squibb continues to evaluate the potential of its therapies for people with blood cancers and disorders who may benefit, while pursuing the next breakthroughs for patients.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science.

The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility.

Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus.

Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle.

Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship.

Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.”

https://news.bms.com/news/corporate-financial/2021/Bristol-Myers-Squibb-Statement-on-Istodax-romidepsin-Relapsed-Refractory-Peripheral-T-cell-Lymphoma-U.S.-Indication/default.aspx

AZ’s Saphnelo approved in US for systemic lupus erythematosus

admin
-
0
AZ’s Saphnelo approved in US for systemic lupus erythematosus

August 02, 2021: “AstraZeneca’s Saphnelo (anifrolumab-fnia) has been approved in the US for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy.

The approval by the Food and Drug Administration (FDA) was based on efficacy and safety data from the Saphnelo clinical development programme, including two TULIP Phase III trials and the MUSE Phase II trial.

In these trials, more patients treated with Saphnelo experienced a reduction in overall disease activity across organ systems, including skin and joints, and achieved sustained reduction in oral corticosteroid (OCS) use compared to placebo, with both groups receiving standard therapy

This marks the first regulatory approval for a type I interferon (type I IFN) receptor antagonist and the only new treatment approved for SLE in more than 10 years.

Type I IFN plays a central role in the pathophysiology of lupus and increased type I IFN signalling is associated with increased disease activity and severity.

Dr. Richard Furie, Chief of the Division of Rheumatology at Northwell Health, New York, US and a principal investigator in the Saphnelo clinical development programme, said: “Our treatment goals in systemic lupus erythematosus are to reduce disease activity, prevent organ damage from either the illness itself or the medications, especially steroids, and improve one’s quality of life.

Today’s approval of anifrolumab represents a big step forward for the entire lupus community.

Physicians will now be able to offer an effective new treatment that has produced significant improvements in overall disease activity, while reducing corticosteroid use.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Today’s landmark approval of Saphnelo is the culmination of years of AstraZeneca’s pioneering research in the type I interferon pathway, a central driver in systemic lupus erythematosus pathophysiology.

This ground-breaking medicine has the potential to meaningfully improve the lives of patients living with this often debilitating disease.”

The adverse reactions that occurred more frequently in patients who received Saphnelo in the three clinical trials included nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster and cough.

SLE, the most common form of lupus affecting up to 300,000 people in the US, disproportionately affects the African-American, Hispanic and Asian populations.

It is a complex autoimmune condition that can affect any organ, and people often experience debilitating symptoms, long-term organ damage and poor health-related quality of life. 

Results from the TULIP-2 Phase III trial were published in The New England Journal of Medicine in January 2020, results from the TULIP-1 Phase III trial were published in The Lancet Rheumatology in December 2019 and results from the MUSE Phase II trial were published in Arthritis & Rheumatology in November 2016.

Saphnelo is under regulatory review for SLE in the EU and Japan.

The Phase III trial in SLE using subcutaneous delivery has been initiated and additional Phase III trials are planned for lupus nephritis, cutaneous lupus erythematosus and myositis.

Financial considerations
AstraZeneca acquired global rights to Saphnelo through an exclusive license and collaboration agreement with Medarex, Inc. in 2004.

The option for Medarex to co-promote the product expired on its acquisition by Bristol-Myers Squibb (BMS) in 2009. Under the agreement AstraZeneca will pay BMS a low to mid-teens royalty for sales dependent on geography.

Systemic lupus erythematosus
SLE is an autoimmune disease in which the immune system attacks healthy tissue in the body.

It is a chronic and complex disease with a variety of clinical manifestations that can impact many organs and can cause a range of symptoms including pain, rashes, fatigue, swelling in joints and fevers.

More than 50% of patients with SLE develop permanent organ damage, caused by the disease or existing treatments, which exacerbates symptoms and increases the risk of mortality.

At least five million people worldwide have a form of lupus.

TULIP-1, TULIP-2 and MUSE
All three trials for Saphnelo (TULIP-1, TULIP-2 and MUSE) were randomised, double-blinded, placebo-controlled trials in patients with moderate to severe SLE who were receiving standard therapy.

Standard therapy included at least one of the following: OCS, antimalarials and immunosuppressants (methotrexate, azathioprine or mycophenolate mofetil).

The pivotal TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) Phase III programme included two trials, TULIP-1 and TULIP-2, that evaluated the efficacy and safety of Saphnelo versus placebo.

TULIP-2 demonstrated superiority across multiple efficacy endpoints versus placebo with both arms receiving standard therapy.

In the trial, 362 eligible patients were randomised (1:1) and received a fixed-dose intravenous infusion of 300mg Saphnelo or placebo every four weeks.

TULIP-2 assessed the effect of Saphnelo in reducing disease activity as measured by the BILAG-Based Composite Lupus Assessment (BICLA) scale.

In TULIP-1, 457 eligible patients were randomised (1:2:2) and received a fixed-dose intravenous infusion of 150mg Saphnelo,300mg Saphnelo or placebo every four weeks, in addition to standard therapy.

The trial did not meet its primary endpoint based on the SLE Responder Index 4 (SRI4) composite measure.

The MUSE Phase II trial evaluated the efficacy and safety of two doses of Saphnelo versus placebo.

In MUSE, 305 adults were randomised and received a fixed-dose intravenous infusion of 300mg Saphnelo, 1,000mg Saphnelo or placebo every four weeks, in addition to standard therapy, for 48 weeks.

The trial showed improvement versus placebo across multiple efficacy endpoints with both arms receiving standard therapy.

In SLE, along with the pivotal TULIP Phase III programme, Saphnelo continues to be evaluated in a long-term extension Phase III trial and a Phase III trial assessing subcutaneous delivery.

In addition, AstraZeneca is exploring the potential of Saphnelo in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus and myositis.

Saphnelo
Saphnelo (anifrolumab) is a fully human monoclonal antibody that binds to subunit 1 of the type I IFN receptor, blocking the activity of type I IFNs.

Type I IFNs such as IFN-alpha, IFN-beta and IFN-kappa are cytokines involved in regulating the inflammatory pathways implicated in SLE.

The majority of adults with SLE have increased type I IFN signalling, which is associated with increased disease activity and severity.”

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/saphnelo-approved-in-the-us-for-sle.html

Coronavirus (COVID-19) Update: July 30, 2021

admin
-
0
Coronavirus (COVID-19) Update: July 30, 2021

July 30, 2021: The U.S. FDA announced the following actions taken in its ongoing response effort to the COVID-19 pandemic:

  • Today, the FDA revised the Emergency Use Authorization (EUA) for REGEN-COV (casirivimab and imdevimab, administered together) to add an authorization of REGEN-COV for emergency use as post-exposure prophylaxis (prevention) for COVID-19 in adults and pediatric individuals (12 years of age and older weighing at least 40 kilograms) who are at high risk for progression to severe COVID-19, including hospitalization or death.

    REGEN-COV is not authorized for pre-exposure prophylaxis to prevent COVID-19 before being exposed to the SARS-CoV-2 virus — only after exposure to the virus.

    REGEN-COV should only be used as post-exposure prophylaxis for specific patient populations.

    Prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19. FDA has authorized three vaccines to prevent COVID-19 and serious clinical outcomes caused by COVID-19, including hospitalization and death.

    FDA urges you to get vaccinated, if you are eligible. Learn more about FDA’s COVID-19 vaccination efforts.
  • On Wednesday, July 28, the FDA revised the EUA for baricitinib (sold under the brand name Olumiant) now authorizing baricitinib alone for the treatment of COVID-19 in hospitalized adults and pediatric patients two years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

    Under the revised EUA, baricitinib is no longer required to be administered with remdesivir (Veklury). Baricitinib is not FDA-approved as a treatment for COVID-19.
  • On Wednesday, the FDA authorized an extension for the shelf life of the refrigerated Janssen (Johnson & Johnson) COVID-19 Vaccine, allowing the product to be stored at 2-8 degrees Celsius for six months.

    This extension from four and a half months to six months was granted following a thorough review of data submitted by Janssen and applies to all refrigerated vials of Janssen COVID-19 Vaccine that have been held in accordance with the manufacturer’s storage conditions.

    The concurrence letter can be read here.

    The expiration dates for vaccines that are authorized under an EUA may be extended based on data submitted by the manufacturers, and in accordance with FDA’s authorization.  Health care providers administering the vaccine should check the company’s website, www.vaxcheck.jnjExternal Link Disclaimer, to obtain the most up-to-date expiration dates for specific lots of the Janssen COVID-19 vaccine. 
  • As part of the FDA’s effort to protect consumers, the agency issued a warning letter to the operator of www.rxmedkart.com for selling unapproved drugs for multiple diseases, including COVID-19. Drugs that have circumvented regulatory safeguards may be contaminated, counterfeit, contain varying amounts of active ingredients or contain different ingredients altogether. Consumers can visit BeSafeRx to learn about how to safely buy medicine online. Consumers concerned about COVID-19 should consult with their health care provider.
  • This week, the FDA added three new frequently asked questions (FAQs) on COVID-19 vaccines and the approval process. The FAQs can be found here and the questions include:
    • Is an approval (or biologics license approval) different from an emergency use authorization? Does it change the availability of COVID-19 vaccines?
    • How long will it take to approve COVID-19 vaccines?
    • How important is it to make sure approved vaccines are available versus other public health measures? Do you have the resources to do this quickly?
  • Testing updates:
    • As of today, 396 tests and sample collection devices are authorized by the FDA under emergency use authorizations (EUAs).

      These include 279 molecular tests and sample collection devices, 86 antibody and other immune response tests and 31 antigen tests. There are 53 molecular authorizations and one antibody authorization that can be used with home-collected samples.

      There is one molecular prescription at-home test, three antigen prescription at-home tests, five antigen over-the-counter (OTC) at-home tests and two molecular OTC at-home tests.
    • The FDA has authorized 12 antigen tests and eight molecular tests for serial screening programs. The FDA has also authorized 593 revisions to EUA authorizations.”

      https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-july-30-2021
1...505152...157Page 51 of 157

EDITOR PICKS

POPULAR POSTS

POPULAR CATEGORY

ABOUT US

LifeProNow provides guidance and high quality contents to help job seekers to get their dream Job. All the contents are written by experienced folks and peer reviewed by experts.

Contact us: [email protected]

FOLLOW US

© LifeProNow | All Rights Reserved