FDA Panel Meetings on Emergency Use Authorization for Boosters, COVID Vaccines for Young Children

 Today, the U.S. Food and Drug Administration is announcing two upcoming meetings of its Vaccines and Related Biological Products Advisory Committee (VRBPAC) to discuss newly available data for the currently available COVID-19 vaccines.

VRBPAC Meeting on Janssen and Moderna COVID-19 Vaccine Boosters 

On Oct. 14 and 15, the advisory committee will meet to discuss the use of booster doses of the Moderna COVID-19 Vaccine and the Janssen COVID-19 Vaccine. Both vaccines are currently authorized for emergency use to prevent COVID-19 in individuals 18 years of age and older. The committee will also hear presentations and discuss the available data on the use of a booster of a different vaccine than the one used for the primary series of an authorized or approved COVID-19 vaccine (heterologous or “mix and match” booster). 

“Vaccines are one of the most important interventions for bringing an end to the ongoing pandemic. It’s critical that as many eligible individuals as possible get vaccinated as soon as possible. Once vaccinated, we want to ensure that individuals continue to be protected against the adverse effects of COVID-19. The available data make clear that protection against symptomatic COVID-19 in certain populations begins to decrease over time, so it’s important to evaluate the information on the use of booster doses in various populations,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. 

On Oct. 14, the committee will discuss an amendment to the emergency use authorization of the Moderna COVID-19 Vaccine for the administration of a booster dose, in individuals 18 years of age and older. 

On Oct. 15, the VRBPAC will discuss amending the emergency use authorization of Johnson and Johnson’s Janssen COVID-19 Vaccine for the administration of a booster dose, in individuals 18 years of age and older. 

Additionally, on Oct. 15, the committee will hear a presentation from the National Institute of Health’s National Institute of Allergy and Infectious Diseases on the heterologous use of booster doses following the primary series of the three currently authorized or approved COVID-19 vaccines. 
   
During the meeting, the committee will hear presentations from the companies on the data for their respective vaccines. The FDA will also present its own analyses of each of the manufacturers’ data. There will be an open public hearing each day during which the public will be given an opportunity to provide comments.

VRBPAC Meeting on Pfizer Data on Its COVID-19 Vaccine for Children 5-11

The FDA anticipates receiving a request from Pfizer to amend its emergency use authorization to allow the use of its COVID-19 vaccine in children 5 through 11 years of age. In anticipation of the request, the FDA is moving forward with scheduling an advisory committee meeting on Oct. 26 to inform the agency’s decision-making.

“We know from our vast experience with other pediatric vaccines that children are not small adults, and we will conduct a comprehensive evaluation of clinical trial data submitted in support of the safety and effectiveness of the vaccine used in a younger pediatric population, which may need a different dosage or formulation from that used in an older pediatric population or adults,” said Acting FDA Commissioner Janet Woodcock, M.D. 

The FDA intends to make background materials for both VRBPAC meetings available to the public, including the meeting agendas and committee rosters, no later than two business days before each meeting. 

The FDA intends to livestream the VRBPAC meetings on the agency’s YouTube page (Oct. 14 meeting linkExternal Link Disclaimer; Oct. 15 meeting linkExternal Link Disclaimer; Oct. 26 meeting linkExternal Link Disclaimer), which will be viewable on the agency’s FacebookExternal Link Disclaimer and TwitterExternal Link Disclaimer channels; the meetings will also be webcast from the FDA website.

https://www.fda.gov/news-events/press-announcements/fda-hold-advisory-committee-meetings-discuss-emergency-use-authorization-booster-doses-and-covid-19

FDA approval tracker: September

 While there were FDA setbacks for Calliditas and Verrica last month there were also a couple of early oncology approvals. One such win was for Tivdak, Seagen/Genmab’s treatment for recurrent or metastatic cervical cancer. However, expected sales of Tivdak could be hit by an unexpected black box warning regarding ocular toxicity. An early approval for Takeda’s Exkivity also came with safety implications. The oral therapy, used to treat lung cancer driven by EGFR exon 20 insertions, has a black box warning for QTc prolongation. J&J’s competing project Rybrevant does not come with a warning, but is less convenient as it is an infused antibody. Separately, Takeda investors are still holding out for FDA news on Eohilia after the FDA's action date was missed in April. Takeda says Eohilia could become the first treatment for eosinophilia oesophagitis, but with a filing for Sanofi/Regeneron’s Dupixent expected next year Takeda will want the regulators to hurry.

Notable first-time US approval decisions in September
Project	Company	Indication(s)	2026e sales by indication ($m)	Outcome
Qulipta (atogepant)	Abbvie	Episodic migraine prevention	954	Approved
Tivdak (tisotumab vedotin)	Seagen/Genmab	Previously treated recurrent or metastatic cervical cancer	629*	Accelerated approval (over 2 weeks early)
Nefecon	Calliditas	IgA nephropathy	629**	Extended to Dec 15
Exkivity (moborcertinib)	Takeda	EGFR exon 20 Insertion+ NSCLC	436	Accelerated approved (over a month early)
Livmarli (maralixibat)	Mirum	Cholestatic pruritus in Alagille syndrome	432	Approved
VP-102	Verrica	Molluscum contagiosum	271*	Second CRL (deficiencies at contract manufacturer)
Eohilia (TAK-721)	Takeda	Eosinophilic esophagitis	187	No decision yet (April Pdufa missed)
Illuccix	Telix	Prostate cancer imaging	42	Extended to December 23
Reltecimod	Atox Bio	Resolution of organ dysfunction in necrotising soft tissue infections	-	Supposed to have been Sep 30, no news released
Epsolay	Sol-Gel	Papulopustular rosacea	-	No decision yet (delayed in Apr)
*Sales by indication not split out, **includes undisclosed partner sales. Source: Evaluate Pharma & company releases

 

 

Supplementary and other notable approval decisions in September
Product	Company	Indication (clinical trial)	Outcome
AVT02 (Humira biosimilar)	Alvotech/Teva	Inflammatory conditions, PK study AVT02-GL-101, efficacy study AVT02-GL-301	Delayed (facility inspection)
Repatha	Amgen	Paediatric patients with heterozygous familial hypercholesterolemia (Hauser-RCT)	Approved
Invega Hafyera (Paliperidone palmitate 6-month, PP6M)	J&J	Adults with schizophrenia (Route 6)	Approved
INP104/ Trudhesa	Impel	505(b)(2) application acute treatment of migraine (dihydroergotamine mesylate with olfactory delivery)	Approved
Brukinsa	Beigene	Marginal zone lymphoma who have received at least one prior anti-CD20-based therapy (Magnolia, Ph1/2)	Approved
Brukinsa	Beigene	Waldenström’s macroglobulinemia (Aspen)	Approved
Opzelura (ruxolitinib cream)	Incyte	Atopic dermatitis (TruE-AD1, TruE-AD2)	Approved
Jakafi	Incyte/Novartis	Paediatric patients with steroid-refractory GvHD (Reach3)	Approved
Byooviz (Lucentis biosimilar)	Biogen/ Samsung Bioepis	Wet AMD, myopic choroidal neovascularisation and macular oedema following retinal vein occlusion	Approved
Erbitux + Braftovi	Lilly/Pfizer	Adult patients with metastatic colorectal cancer with a BRAF V600E mutation (Beacon CRC)	Approved
Source: Evaluate Pharma, company releases & clinicaltrials.gov https://www.evaluate.com/vantage/articles/news/snippets/us-fda-approval-tracker-september-0

Unexpected win opens the way to an oral Covid antiviral

 If Merck’s acquisition of Acceleron yesterday had been widely expected the same cannot be said of today’s positive results for the group’s Covid-19 antivital molnupiravir. The Ridgeback Biotherapeutics-partnered project had already failed in hospitalised subjects, so today’s pivotal study success in outpatients is a major shot in the arm.

With analysts hailing the data, from a planned interim analysis of the Move-Out trial, a “game changer”, Merck opened up 10% this morning, equivalent to a market cap increase of almost $20bn. The success comes in contrast to the lacklustre performance of some other Covid treatments, and marks a turnaround for molnupiravir, a repurposed flu antiviral.

As Vantage Analysis had pointed out, the pipeline for oral antivirals for Covid-19 was looking thin. Merck itself, in addition to scrapping part of its molnupiravir work, had abandoned MK-7110, a separate project it had gained via Oncoimmune, in hospitalised patients after an FDA request for more data made it unviable for the coronavirus in the short term.

Oral game-changer

Today the story is quite different, however, and molnupiravir's oral dosing is the main reason why this is being hailed as such a success. The convenience of a drug that can be taken as a tablet, at home, within five days of Covid-19 symptoms starting, cannot be understated.

Not only that, but Move-Out has shown a 50% reduction in risk of hospitalisation or death, Merck said today, hitting a p value of 0.0012 at an interim analysis triggered by the evaluation of the first 775 of a total 1,550 mild-to-moderate Covid-19 patients. A decision to stop recruitment based on compelling interim efficacy was taken on August 5, Merck said, with over 90% of the total enrolled, and full analysis is forthcoming.

The only US-approved antiviral is Gilead’s Veklury, but this has the disadvantage of IV dosing. Moreover, its clinical backing is somewhat unconvincing: two trials showed an improved time to recovery versus placebo but a third did not, and no decrease in mortality has been demonstrated with Veklury.

Remaining existing competition in the treatment setting comes from antibodies. Regeneron’s Regen-Cov, a combo of the MAbs casirivimab and imdevimab, and Lilly/Abcellera’s bamlanivimab plus etesevimab are both available under emergency use authorisation for post-exposure prophylaxis, and both have demonstrated reductions in hospitalisation or death.

However, like Veklury both have to be injected. Another MAb combo, Astrazeneca’s AZD7442, does have the convenience of intramuscular dosing and a long half life, but failed in post-exposure prophylaxis. It did succeed in pre-exposure prophylaxis, but clearly this is a separate market from the treatment setting Merck is now targeting.

Oral antivirals for treating Covid-19
Project	Company	Setting	Note
Molnupiravir	Merck & Co/Ridgeback	Ph3 in outpatients succeeded (Move-Out, NCT04575597); Ph2/3 in hospitalised pts terminated (Move-In; NCT04575584)	Repurposed flu antiviral
AT-527	Roche/Atea	Ph3 in outpatients ends Nov 2021 (Morningsky, NCT04889040)	Repurposed hep C antiviral
PF-07321332	Pfizer	Ph3 in low-risk outpatients ends Oct 2021 (NCT05011513) Ph3 in high-risk outpatients ends Nov 2021 (NCT04960202)	Ritonavir combo
Favipiravir	Appili	Ph3 in outpatients ends Sep 2021 (Preseco, NCT04600895)	Repurposed flu antiviral
Upamostat	Redhill Biopharma	Ph2/3 in outpatients ends Sep 2022 (NCT04723537)	Repurposed oncology project (Mesupron)
Source: Evaluate Pharma & clinicaltrials.gov.

The Move-Out data have yet to be scrutinised in full, but the interim readout breaks down into a 39% reduction in day-29 hospitalisation, and zero deaths on molnupiravir versus eight on placebo. It will be important for these data to hold up at final analysis.

Other reasons for optimism is that Merck said the results were consistent across the viral variants Gamma, Delta and Mu in patients where sequencing had been carried out. Logically, Merck intends to file for US emergency use authorisation.

In terms of competition the next dataset to look out for will come from Roche/Atea’s AT-527, Pfizer’s PF-07321332 and Appili's favipiravir, but beyond that the oral antiviral space looks bleak. Illustrating the game-changing nature of an oral Covid-19 treatment, Atea this morning traded up 20%, while the MAb players Regeneron and Abcellera were off 7% and 8% respectively.

A final point to consider is why this took Merck so long; Move-Out had begun last October, yet with the Covid-19 pandemic raging in many of the countries in which the trial was run it took 10 months to generate 775 patients’ worth of 29-day data. Perhaps this illustrates just how low hopes had been.

https://www.evaluate.com/vantage/articles/news/trial-results/unexpected-win-opens-way-oral-covid-antiviral

Merck pill seen as 'huge advance,' raises hope of preventing COVID-19 deaths

 Co will seek U.S. approval for pill as soon as possible

* If approved, would be 1st oral antiviral COVID-19 drug

* Merck shares rally, some vaccine makers fall

* U.S govt to buy 1.7 mln courses at $700 each (Adds White House official, details on potential side effects, updates shares)

An experimental antiviral pill developed by Merck & Co could halve the chances of dying or being hospitalized for those most at risk of contracting severe COVID-19, according to data that experts hailed as a potential breakthrough in how the virus is treated.

If it gets authorization, molnupiravir, which is designed to introduce errors into the genetic code of the virus, would be the first oral antiviral medication for COVID-19.

Merck and partner Ridgeback Biotherapeutics said they plan to seek U.S. emergency use authorization for the pill as soon as possible and to make regulatory applications worldwide.

“An oral antiviral that can impact hospitalization risk to such a degree would be game changing,” said Amesh Adalja, senior scholar at the Johns Hopkins Center for Health Security.

Current treatment options include Gilead Sciences Inc’s infused antiviral remdesivir and generic steroid dexamethasone, both of which are generally only given once a patient has already been hospitalized.

“This is going to change the dialogue around how to manage COVID-19,” Merck Chief Executive Robert Davis told Reuters.

Existing treatments are “cumbersome and logistically challenging to administer. A simple oral pill would be the opposite of that,” Adalja added.

The results from the Phase III trial, which sent Merck shares up more than 9%, were so strong that the study is being stopped early at the recommendation of outside monitors.

Shares of Atea Pharmaceuticals Inc, which is developing a similar COVID-19 treatment, were up more than 21% on the news.

Shares of COVID-19 vaccine makers here Moderna Inc were off more than 10%, while Pfizer was down less than 1%.

Jefferies analyst Michael Yee said investors believe “people will be less afraid of COVID and less inclined to get vaccines if there is a simple pill that can treat COVID.”

Pfizer and Swiss drugmaker Roche Holding AG are also racing to develop an easy-to-administer antiviral pill here for COVID-19. For now, only antibody cocktails that have to be given intravenously are approved for non-hospitalized patients.

White House COVID-19 response coordinator Jeff Zients said on Friday that molnupiravir is “a potential additional tool... to protect people from the worst outcomes of COVID,” but added that vaccination “remains far and away, our best tool against COVID-19.”

A planned interim analysis of 775 patients in Merck’s study looked at hospitalizations or deaths among people at risk for severe disease. It found that 7.3% of those given molnupiravir twice a day for five days were hospitalized and none had died by 29 days after treatment. That compared with a hospitalization rate of 14.1% for placebo patients. There were also eight deaths in the placebo group.

“Antiviral treatments that can be taken at home to keep people with COVID-19 out of the hospital are critically needed,” Wendy Holman, Ridgeback’s CEO, said in a statement.

‘A HUGE ADVANCE’

Scientists welcomed the potential new treatment to help prevent serious illness from the virus, which has killed almost 5 million people around the world, 700,000 in the United States.

“A safe, affordable, and effective oral antiviral would be a huge advance in the fight against COVID,” said Peter Horby, a professor of emerging infectious diseases at the University of Oxford.

The study enrolled patients with laboratory-confirmed mild-to-moderate COVID-19, who had symptoms for no more than five days. All patients had at least one risk factor associated with poor disease outcome, such as obesity or older age.

Drugs in the same class as molnupiravir have been linked to birth defects in animal studies. Merck has said similar studies of molnupiravir – for longer and at higher doses than used in humans – indicate that the drug does not affect mammalian DNA.

Merck said viral sequencing done so far shows molnupiravir is effective against all variants here of the coronavirus including the highly transmissible Delta, which has driven the recent worldwide surge in hospitalizations and deaths.

It said rates of adverse events were similar for both molnupiravir and placebo patients, but did not give details.

Merck has said data shows molnupiravir is not capable of inducing genetic changes in human cells, but men enrolled in its trials had to abstain from heterosexual intercourse or agree to use contraception. Women of child-bearing age in the study could be pregnant and also had to use birth control.

The U.S. drugmaker said it expects to produce 10 million courses of the treatment by the end of 2021.

The company has a U.S. government contract to supply 1.7 million courses of molnupiravir at a price of $700 per course.

Davis said Merck has similar agreements with other governments, and is in talks with more. Merck said it plans a tiered pricing approach based on country income criteria.

Merck has also agreed to license the drug to several India-based generic drugmakers, which would be able to supply the treatment to low- and middle-income countries.

Molnupiravir is also being studied in a Phase III trial for preventing infection in people exposed to the coronavirus.

Merck officials said it is unclear how long the FDA review will take, although Dean Li, head of Merck’s research labs, said, “they are going to try to work with alacrity on this.”

https://www.reuters.com/article/health-coronavirus-merck-treatment/update-4-merck-pill-seen-as-huge-advance-raises-hope-of-preventing-covid-19-deaths-idUSL1N2QX0QJ

Cal. 1st State To Require Students Be Vaccinated To Attend School

 Fresh of his victory in the gubernatorial runoff, California Gov. Gavin Newsom just announced that California's schools will soon require all eligible public and private school students in 7th grade and higher in the Golden State to be vaccinated against COVID, a first-in-the-nation policy that Newsom says will impact millions of students by fall 2022, or possibly sooner.

The mandate would impact students in grades 7 through 12 and will be imposed during the next semester after (and assuming) the FDA gives full approval for vaccines for children ages 12 and older.

"This is just another vaccine," Newsom said during a news conference after he announced the "state-wide" mandate, claiming the COVID jab would join "a well-established list that currently includes 10 vaccines and well-established rules and regulations that have been advanced by the Legislature for decades."

Readers can watch the clip below:

Once the vaccines are approved for use in younger students, they will likely be phased in. Apparently, it doesn't matter whether COVID is still a problem by then or not.

The mandate could take effect for students 12 and older as early as January 2022, if full federal approval comes along by then, the governor said during live remarks at a San Francisco school.

Presently, the vaccine is only approved for patients aged 16 or older, though Pfizer has published trial results and submitted them to the FDA, suggesting approval for students aged 12 o 15 could likely come before the end of the year. If this happens, all students in 7th grade and above will be required to get the vaccine, or attend online school - or home school - permanently.

Medical and religious exemptions will be offered, Newsom said.

What's more, vaccines for students aged 5 to 11 are not that far off, which means the state could soon extend its requirements to all children in Kindergarten or older. Pfizer is expected to apply for authorization imminently with evidence that shows its vaccine is safe for children in that age range.

California was famously the first state to lock down, minting the "two weeks to stop the spread" slogan that's remembered.

https://www.zerohedge.com/political/california-becomes-first-state-require-students-be-vaccinated-attend-school/

Why Vir Biotechnology Stock Is Sinking

 Shares of Vir Biotechnology (NASDAQ:VIR) were sinking last week. Vir was pulled down by the overall stock market sell-off earlier this week. However, its shares really took a dive after Goldman Sachs analyst Paul Choi downgraded the company from buy to neutral.

It's best to avoid making investment decisions based on analysts' downgrades (and upgrades, for that matter). However, you can sometimes learn things by understanding why a given analyst is bearish about a given stock.

In this case, though, Choi actually isn't bearish about Vir. Yes, he downgraded the biotech stock, and even lowered his 12-month price target. However, that price target still reflects a 14% upside from the stock's closing price at the end of last week and a 39% premium to the current share price.

Vir and its partner GlaxoSmithKline (NYSE:GSK) appear to have a winner with monoclonal antibody sotrovimab in treating COVID-19. Sotrovimab has won Emergency Use Authorization (EUA) in the U.S. and authorizations or approvals in several other key markets, including the European Union. Australia recently quadrupled its order of the monoclonal antibody after physicians reported positive results in treating COVID-19 patients.

Vir should have several potential catalysts on the way. GlaxoSmithKline and Vir plan to file for full U.S. Food and Drug Administration approval of sotrovimab later this year. Results from a late-stage study of the therapy in treating mild-to-moderate COVID-19 are expected within the next few months.

Vir also expects to report initial data in the first half of 2022 from a phase 2 study of a combination of VIR-2218 and VIR-3434 as a potential cure for chronic hepatitis B virus infection.

https://www.fool.com/investing/2021/09/24/why-vir-biotechnology-stock-is-sinking-this-week/

Adagio's COVID Candidate Shows Prolonged Half-Life, Neutralization At 6 Months

 

• Adagio Therapeutics Inc (NASDAQ: ADGI) has announced new data from its COVID-19 antibody program.

• The Company is evaluating ADG20 in Phase 1 single ascending dose study of ADG20 ex vivo against SARS-CoV-2.

• Data from a six-month evaluation timepoint confirmed the extended half-life of ADG20, which approached 100 days based on data from the 300 mg intramuscular (IM) dose that was given as a single injection.

• In addition, 50% serum virus neutralization titers at six months after a 300 mg IM dose of ADG20 were similar to observed peak titers with the Moderna Inc's (NASDAQ: MRNA) mRNA-1273 vaccine and exceeded those achieved with the AstraZeneca Plc's (NASDAQ: AZN) AZD1222 vaccine series, the Company reported.

• ADG20 was well-tolerated with no study drug-related adverse events (AEs), serious AEs, or injection-site or hypersensitivity reactions.

• Participants will continue to be followed through for 12 months.

• Adagio anticipates that the data will support an Emergency Use Authorization application in Q1 of 2022.

• Data from quantitative systems pharmacology/whole-body physiologically based modeling support evaluation of 300 mg intramuscular dose of ADG20 as a single injection in Phase 2/3 studies

https://finance.yahoo.com/news/adagios-covid-19-candidate-shows-133359603.html