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Wednesday, March 2, 2022

Pfizer Granted FDA Breakthrough Therapy Designation for RSV Vaccine Candidate

 Pfizer Inc. (NYSE:PFE) today announced that its respiratory syncytial virus (RSV) vaccine candidate, PF-06482077 or RSVpreF, received Breakthrough Therapy Designation from the US Food and Drug Administration (FDA) for prevention of RSV-associated lower respiratory tract illness in infants from birth up to six months of age by active immunization of pregnant women.

The FDA decision is informed by the results of the Phase 2b proof-of-concept study of RSVpreF (NCT04032093), a global, double-blinded, placebo-controlled study that assessed the safety and immunogenicity of RSVpreF in healthy pregnant women ages 18 through 49 years old, who were vaccinated between 28- and 36-weeks gestation, and their infants. Pfizer will publish outcomes from this clinical trial at a future date.

https://www.businesswire.com/news/home/20220302005162/en/Pfizer-Granted-FDA-Breakthrough-Therapy-Designation-for-Respiratory-Syncytial-Virus-RSV-Vaccine-Candidate-for-the-Prevention-of-RSV-in-Infants-from-Birth-up-to-Six-Months-of-Age-by-Active-Immunization-of-Pregnant-Women

Sanofi makes another pipeline deal, tapping Adagene for antibody tech

 Sanofi’s rash of dealmaking has continued with a $2.5 billion tie-up with Chinese cancer immunotherapy biotech Adagene, focused on developing a new generation of safer antibody-based therapies.

The French drugmaker is paying $17.5 million upfront to kick off the collaboration, which will see Adagene’s SAFEbody technology applied to monoclonal and bispecific antibodies for a range of immuno-oncology applications. Another $2.5 billion is in the offing in future milestone payments.

SAFEbody is a masking technology that aims to ensure that antibodies are only activated in diseased tissues, lowering the risk of toxicity elsewhere in the body. The two partners aim to apply the technology to a pair of Sanofi drug candidates, the identify of which has not yet been disclosed.

Sanofi’s ambitions in immuno-oncology are spearheaded by its Regeneron-partnered PD-1 checkpoint inhibitor Libtayo (cemiplimab), which still has modest sales, and the drugmaker has been keen to acquire new assets that may have potential in combination therapies.

Suzhou-based Adagene will carry out the work required to make the masked antibodies, with Sanofi taking responsibility for later stage research and all the clinical, development and commercialisation work on the drugs.

Adagene chief executive Peter Luo said that the deal with Sanofi is an endorsement of SAFEbody, saying the technology “enables dynamic and precise target engagement by our antibody-based therapeutics, which are tailor made to overcome the fundamental challenges in oncology drug development today.”

The Chinese company is deploying the technology in its in-house pipeline in AG126, an antibody prodrug targeting the immune checkpoint CTLA4. That’s the same target as Bristol-Myers Squibb’s Yervoy (ipilimumab), which is approved to treat a long list of solid tumours but is notoriously hard to tolerate.

While early-stage, the Adagene deal is another example of Sanofi’s determination to bolster its R&D pipeline via a string of deals, including a $5.2 billion, strategic-level alliance with UK artificial intelligence company Exscientia covering up to 15 development programmes.

That followed last year’s $3.2 billion takeover of mRNA firm Translate Bio and the acquisitions of immuno-oncology Amunix – another immuno-oncology specialist – and Kadmon Pharma for $1 billion and $1.9 billion, respectively. It also made smaller bolt-on deals with the likes of ABL, Owkin and Gyroscope.

Earlier in 2021 Sanofi also bought Kymab and its atopic dermatitis drug KY1005 for $1.1 billion upfront.

https://pharmaphorum.com/news/sanofi-makes-another-pipeline-deal-tapping-adagene-for-antibody-tech/

Fitbit recalls 1.7 million smartwatches due to burn risk

 Fitbit recalled 1.7 million smartwatches that pose a burn hazard because the lithium-ion battery inside can overheat, the U.S. Consumer Product Safety Commission announced Wednesday.

One million of the affected watches were sold in the U.S., while about 693,000 were sold internationally, according to the commission's recall notice.

So far, Fitbit has gotten 115 reports in the U.S. and 59 reports internationally of the battery overheating.

Two out of 78 people who reported burn injuries in the U.S. have suffered third-degree burns. Forty people abroad have reported burn injuries. Many people wear the devices to bed to track their sleep.

The recall specifically involves the Fitbit Ionic Smartwatch. The watches were sold in slate blue/burnt orange, charcoal/smoke gray, blue gray/silver gray, and a special edition co-branded with Adidas in ink blue/silver gray. Model number FB503 is printed on the back of the device next to where the band attaches.

The watches were sold at Best Buy, Kohl’s, Target, on Amazon.com and Fitbit.com from September 2017 through December 2021. Fitbit stopped making the watch in 2020.

The commission urged customers to "immediately stop using the recalled Ionic smartwatches and contact Fitbit to receive pre-paid packaging to return the device." Those who return the device will receive a $299 refund and a discount code for 40 percent off some Fitbit devices.

https://www.nbcnews.com/tech/gadgets/fitbit-recalls-17-million-smartwatches-due-burn-risk-rcna18259

How Operation Warp Speed clashed with Pfizer in the early days of the pandemic

 Operation Warp Speed, perhaps the brightest spot in former President Donald Trump’s Covid-19 legacy, helped hurry the development and distribution of Pfizer and Moderna’s lifesaving Covid-19 vaccines at a pace never before imagined.


One of the central figures in and around the now-defunct OWS was Paul Mango, former deputy chief of staff at HHS who led the media calls around Covid-19 and worked closely with former HHS Secretary Alex Azar.


Mango has penned a new book on his time at OWS leading up to the vaccines, which hits the shelves on May 18.



An advance copy of the book, known as Warp Speed: Inside the Operation That Beat COVID, the Critics, and the Odds, delivers several surprising behind-the-scenes struggles between Warp Speed and Pfizer, a company that insists it never took any government support for its Covid-19 vaccine.


But Mango’s book explains more of the details on how Pfizer’s vaccine struggled at the beginning, what Pfizer did take from OWS, and how the Big Pharma was reliant on the federal government for several key tasks.


In outlining the central issues for Warp Speed, Mango points to Pfizer, which sold 100 million doses of its vaccine for $1.95 billion to the US, as one of three main sources of tension.


When the vaccines first began rolling out, Mango explains how Pfizer pledged in September 2020 that it would likely deliver 50 million doses to the US before year’s end.


“As the autumn wore on, however, Pfizer began reducing the numbers of doses we could expect to receive,” Mango writes.


The doses were eventually delivered in a trickle in early December, Mango says, but Pfizer shifted its promise to 22 million doses, and ended up only providing 18 million.


“Needless to say, in those early weeks, when it came to Pfizer’s manufacturing process, we had little confidence at all,” Mango writes.


Pfizer has since distributed more Covid-19 doses than just about any other company and hauled in more than $20 billion in vaccine sales last year worldwide. Pfizer CEO Albert Bourla is also writing his own book that may explain some of this situation more. But still, Mango insists that Pfizer was the toughest to deal with.


“Of all the companies in which we invested, Pfizer was both the least transparent and least collaborative. It would not let us observe its manufacturing processes for months and then failed to deliver the contracted amounts of doses it promised in November and December of 2020. This eroded the credibility of the GEN [Gustave] Perna’s distribution team in the eyes of many governors,” Mango writes.


Similarly, Mango, a West Point graduate who also served as chief of staff at CMS, noted the “only problem” Warp Speed encountered among 18 uses of the Defense Production Act to prioritize certain supplies, was with Pfizer.


“It is hard to know for sure, but politics may have been at least partially behind Pfizer’s generally difficult stance toward OWS, even while depending heavily on our assistance with packaging, distributing, and administering its doses,” Mango writes, adding:


For a long time, Pfizer declined to answer these questions yet voiced frustration with not receiving a priority rating under the DPA. We speculated that the company intended to use the DPA to help it manufacture vaccines that would be shipped overseas, which, in many cases, the DPA prohibited. In the late fall, Pfizer began to encounter serious raw material and spare parts constraints. Only then did it comply with the DPA’s requirements and receive (in December) a priority rating.


Pfizer did not respond to a request for comment.


The GAO also noted in a report from last April that the Department of Defense worked with all of the companies but Pfizer to negotiate additional government rights requiring vaccine developers to license their IP so that a contract manufacturer may produce the vaccine for exclusive sale to the government.


“According to DOD officials, DOD was unable to negotiate with Pfizer to include third party manufacture as a remedy in its agreement due to the government’s lack of involvement in the Pfizer vaccine’s development. Pfizer officials noted that Pfizer’s agreement does not allow the government to ‘march-in,’ as that term is defined in 35 U.S.C. § 203, and according to their agreement, government funding was limited to payment for doses,” the GAO report says.



Mango also reflects on the tension between Moncef Slaoui, Warp Speed’s disgraced chief scientific advisor who has since been let go from several biotechs and boards due to sexual harassment, and Deborah Birx, the White House coronavirus task force coordinator.


Whereas Slaoui insisted on advancing six vaccine candidates across three different tech platforms, Birx told the team to focus “on only one of these three platforms, a tried-and-tested technology referred to as ‘protein sub-unit’ being utilized by two of our vaccine candidate companies Novovax and Sanofi,” according to Mango.


Hindsight is 20/20, but neither the Novovax nor the Sanofi Covid-19 vaccines have received an EUA yet.


And whereas Warp Speed helped NIH build Moderna’s Covid-19 vaccine from the ground up, making the EUA a momentous occasion, Mango notes that the Pfizer EUA:


Did not have the same emotional impact on our team. It wasn’t even really a Pfizer vaccine. Distributed by Pfizer, BioNTech, a small company in Germany, actually developed it. While heavily supported by Operation Warp Speed in many ways, including a $2 billion advanced purchase order for 100 million doses, Pfizer consistently chose to operate at arm’s length. So, we did not feel nearly the personal ownership of Pfizer’s success as we did of Moderna’s.

https://endpts.com/how-operation-warp-speed-clashed-with-pfizer-in-the-early-days-of-the-pandemic/

CDC data suggest Pfizer vaccine protection holds up in kids 5-11, raising questions on earlier study

 Does the Pfizer-BioNTech Covid-19 vaccine provide less protection to children aged 5 to 11 than to adolescents 12 to 17? A study from New York state released Monday suggests that’s the case. But new data from 10 states released Tuesday tell a different story.

The data, published by the Centers for Disease Control and Prevention, suggest that two doses of the Pfizer vaccine aren’t very protective against infection for either age group in the face of the Omicron variant, but that protection against severe illness appears to be holding up equally in both sets of children.

They do not suggest more rapid waning, or more marked waning, among the younger group of children.

“When you look at the whole picture, we’re not seeing that signal that New York state is seeing,” Ruth Link-Gelles, the CDC’s program manager for Covid vaccine efficacy studies, told STAT in an interview.

In addition to the study, published in the CDC’s journal Morbidity and Mortality Weekly Report, the agency was to post statistics from other datasets on its website Tuesday afternoon. The various data sources tell the same story, Link-Gelles said. “They’re seeing actually very similar rates of disease among the 5- to 11-year-olds and the 12-to-15s. Where they see the difference is between the unvaccinated and vaccinated.”

On Monday, a preprint — a scientific paper that has not yet been peer-reviewed or published in a journal — was posted on a server by researchers with the New York State Department of Health.

Those data show a rapid and substantial decline in protection after vaccination in children in the younger age group, with efficacy against infections dropping off more quickly and dramatically than the declines seen in children aged 12 to 17. The study also found a significant, but less steep, decline in protection against hospitalizations.

The researchers noted a sharp difference in the protection seen in 11-year-olds and 12-year-olds, children on either side of the divide between the pediatric dose of the Pfizer vaccine and the adult dose. Adults get two shots 21 days apart; each jab contains 30 micrograms of vaccine; for the purpose of dosing, anyone 12 years of age and older is an adult. Children 5 to 11 get two doses on the same schedule, but their jabs contain one-third as much vaccine, 10 micrograms, as the adult dose.

“Our data support vaccine protection against severe disease among children 5-11 years, but suggest rapid loss of protection against infection, in the Omicron variant era,” the New York state researchers wrote. “Should such findings be replicated in other settings, review of the dosing schedule for children 5-11 years appears prudent.”

STAT requested an interview with Eli Rosenberg, the senior author of the New York state paper. But he was not made available.

In the study published by the CDC, vaccine effectiveness against emergency department or urgent care visits during the time when the Omicron variant was circulating was between 34% to 45% for adolescents ages 12 through 17 and 51% for children ages 5 through 11. Vaccination of children aged 5 through 11 only began in November so they were likely more recently vaccinated — with higher antibody levels — than children aged 12 to 17 during that period.

Kathryn Edwards, a vaccine expert at Vanderbilt University, said she is not yet convinced the dose used in 5- to 11-year-olds was too low. Rather, Edwards said, what’s clear from both studies is that in both the younger and older children, two doses of vaccine are not enough to fend off Omicron-variant SARS-CoV-2 viruses.

“I don’t think that there really are any data to suggest that the 5- to 11-year-olds is much worse off than the 12- to 15-year-olds, with the Omicron predominance,” Edwards said. “I think that the better part of valor is to say that we need to look at data from more than a single source.”

“The data from New York suggested that there was poor protection for the 5- to 11-year-olds, but certainly this,” she said, referring to the CDC published paper, “would not suggest this.”

Both Edwards and Link-Gelles said more study, over a longer period of time, is going to be needed to get a true sense of how well the Pfizer vaccine is working in children. “I think it’s very early to be making the kind of conclusion that they did,” Link-Gelles said about the New York state paper.

https://www.statnews.com/2022/03/01/cdc-data-suggest-pfizer-vaccine-protection-holds-up-in-kids-5-11-raising-questions-on-earlier-study/

Cabaletta Bio Gets Fast Track Designation for Autoantibody Receptor

 Cabaletta Bio Inc. said the U.S. Food and Drug Administration has granted Fast Track Designation for muscle-specific kinase chimeric autoantibody receptor T, or MuSK-CAART cells, to improve activities of daily living and muscle strength in patients with MuSK antibody-positive myasthenia gravis.

The biotechnology company said MuSK-CAART is being evaluated as a potential treatment for patients with MuSK-associated myasthenia gravis.

Cabaletta's Investigational New Drug application was recently cleared by the FDA within the routine 30-day review period.

The FDA's Fast Track process is intended to facilitate the expedited development and review of therapeutics intended to treat serious or life-threatening conditions and to address unmet medical needs.

https://www.marketscreener.com/quote/stock/CABALETTA-BIO-INC-70835225/news/Cabaletta-Bio-Gets-Fast-Track-Designation-for-Autoantibody-Receptor-39623790/

Inovio lab tests show COVID vaccine weaker against Omicron, trial enrollment paused

 Inovio Pharmaceuticals Inc has paused enrollment for an ongoing late-stage study of its lead COVID-19 vaccine candidate after the shot showed significantly lower levels of antibodies against the Omicron variant in lab testing.

The vaccine, INO-4800, maintained robust T-cell response in the lab tests though, leading Inovio to plan changes to the trial design and forecast a delay in reporting preliminary efficacy data from the study. T-cells are a key part of the immune system's second line of defense.

The company plans to seek regulatory approval to change the main goal of the study to "prevention of severe disease due to COVID-19" from the earlier goal of "prevention of virologically confirmed COVID-19 disease", it said on Tuesday.

"The expectation for vaccination has changed. The highly infectious nature of Omicron has meant that while vaccines currently available in the market may not directly prevent infections, they can significantly protect the vaccinated from severe disease," Chief Executive Officer Joseph Kim said during a call with investors.

An independent data safety monitoring board recommended that Inovio pause enrollment to reflect Omicron's potential impact on the trial. As a result, interim efficacy data from the trial will not be available in the first half of 2022 as previously expected.

In November, Inovio resumed the late-stage trial of its vaccine in the United States after 14 months on clinical hold.

The FDA in September put the study on hold as it sought more information from the company, including details on a delivery device used to inject genetic material into cells.

Inovio then started late-stage trials outside the United States in partnership with China's Advaccine Biopharmaceuticals.

https://www.marketscreener.com/quote/stock/INOVIO-PHARMACEUTICALS-I-17937428/news/Inovio-lab-tests-show-COVID-vaccine-weaker-against-Omicron-trial-enrollment-paused-39630573/