J&J mulls switch from non-profit status for COVID jab

 Johnson & Johnson has been offering its COVID-19 vaccine for sale on a no-profit basis since it became available, but is thinking about a possible switch to a standard commercial model next year or in 2023.

That was the position stated by J&J’s executive vice president Ashley McEvoy on the company’s third-quarter results call yesterday, at which the company reported sales of $502 million for the Ad26.COV2.S vaccine for the three-month period.

“As we continue to work through and fulfil our existing contracts that we have throughout the globe – and as we move into more of a booster market in later 2022, potentially into 2023 – we’d be looking at moving into a more of a commercial market,” she said.

J&J’s vaccine is currently being provided under emergency use authorisations, and the pivot to a commercial model will depend on securing full approval, but McEvoy indicated that regulatory filings are coming soon.

J&J is predicting that total sales of the shot should reach $2.5 billion for the full-year, in line with earlier estimates but indicating an acceleration in the coming months given that total turnover in 2021 so far is $766 million.

Last week, an FDA advisory committee voted unanimously to recommend emergency-use of a booster dose of the COVID-19 vaccine for adults aged 18 and older, which should help drive demand if the FDA follows its advice and approves the new use.

On the other hand, there have been suggestions that boosters may be offered with Moderna or Pfizer/BioNTech, as giving these as second dose after the J&J primary stimulated higher antibody levels than a second dose of Ad26.COV2.S.

Overall sales at J&J rose just under 11% to $23.3 billion – a little below analyst forecasts – with prescription drug sales up nearly 14% to $13 billion.

Star performers were Tremfya (guselkumab) for psoriasis and psoriatic arthritis, up 64% to $537 million in the quarter, as well as oncology stalwart Darzalex (daratumumab) which grew almost44% to $1.6 billion.

https://pharmaphorum.com/news/jj-mulls-switch-from-non-profit-status-for-covid-jab/

Nearly 1,900 Washington state workers quit, are fired over COVID vax mandate

 About 3% of the 63,000 Washington state workers subject to Gov. Jay Inslee’s COVID-19 vaccine mandate have left their jobs or were terminated as this week’s deadline passed.

So far, 1,887 state employees were terminated or left their positions over the mandate that they be fully vaccinated by Oct. 18 or lose their jobs, according to the Office of Financial Management.

Another roughly 3%, or 1,927 workers, received an accommodation that allows them to work in a less-public role without being vaccinated.

An additional 4.6% of state workers — nearly 2,900 — are still in a state of flux, according to a statement by OFM Tuesday afternoon.

That means they may have more time to get the vaccine or could be retiring, according to OFM. Others in that group could still be waiting to see if they get an accommodation — and if not, could still lose their jobs. Those outcomes will be determined in the weeks to come.

Of the state workers still employed, more than 92% are verified as vaccinated.

“The high number of state employees who have gotten vaccinated is good news,” wrote Inslee spokesperson Tara Lee in an email. “Good for the workers, their colleagues and the people they serve.

“While we are sorry to see that 3% go and we wish them well, we are pleased that it is not higher,” she added.

The vaccination push came as a fifth COVID-19 wave slammed into the state. It struck the unvaccinated particularly hard, causing a spike in deaths and hospitalizations across rural Washington, where vaccination rates have lagged behind urban areas.

In August, the governor put in place some of the strictest mandates in the nation, requiring state and school employees — as well as hundreds of thousands of health care workers — to get the jabs or lose their jobs.

But with the deep division and politicization over the pandemic and public health measures to curb it, Inslee’s mandates spurred protests, lawsuits and fierce backlash from conservatives.

In a statement Tuesday, conservative Republicans slammed the departure of workers and again decried Inslee’s use of emergency powers since the pandemic began.

“But I don’t think any of us realized it would come to this, and I think many in the state Legislature are having second thoughts today,” said Sen. Jeff Wilson, R-Longview, in prepared remarks. “Other states are requiring vaccinations, but none of them have taken it to the level of mass terminations. When one person makes all the decisions, there can be no question who is at fault.”

As workers protested the mandate, there were concerns that an exodus could hurt the government’s ability to provide services, from prisons and highway patrols to child-abuse investigations.

The high vaccination rates, however, have dampened some of those concerns.

At the Department of Corrections, about 350 workers — roughly 4.5% of the agency workforce — are leaving. But those numbers are spread out across 12 prisons, plus the administrative headquarters and other offices.

“All facilities have adequate staffing for operations,” wrote DOC spokesperson Rachel Ericson in an email.

The employees leaving state service range from a custodian at the Capitol campus to Washington State Patrol troopers around the state and Washington State University football coach — and highest-paid public employee — Nick Rolovich.

Numbers at other large agencies in recent days, according to their spokespeople, included:

● At the Department of Social and Health Services, 92% of 15,670 workers have been verified as vaccinated. About 3% have received an accommodation that allows them to keep working without the vaccine. Another 2% — or roughly 313 workers — have been let go. The remaining workers have a request for accommodation pending or have started the vaccination process.

● At the Washington Department of Transportation, 402 employees are leaving over the mandate, according to that agency. That includes about 130 workers in the ferries division, which alone employs roughly 2,000.

● At the Department of Fish and Wildlife, about 38 staff — or 2% of the agency’s workforce — lost their jobs over the mandate.

● At the Washington State Patrol, 127 individuals had left over the mandate, or nearly 6% of the agency workforce.

Those departures included, according to WSP, 53 civil servants and 74 commissioned officers: 67 troopers, 6 sergeants, and 1 captain.

“We will miss every one of them,” said Chief John R. Batiste in a statement Tuesday morning. “I truly wish that you were staying with us. You have my utmost appreciation for the hard and successful work that you have provided during your valued WSP careers. You will forever have our respect for your courage and your commitment in all you have done on behalf of the agency.”

Later on Tuesday morning, the Spokane County Sheriff’s Office — which does not have a vaccine mandate in place — was posting recruiting notices on social media.

In a tweet, the office called out to troopers and other law enforcement subject to mandates.

“Looking for a place where you are appreciated & wanted?” read the tweet, which included a recruitment video featuring Sheriff Ozzie Knezovich. “Please contact a member of our Recruitment Team today.”

https://www.seattletimes.com/seattle-news/politics/nearly-1900-washington-state-workers-quit-or-are-fired-over-covid-vaccine-mandate/

U.S. readies plan to vaccinate kids ages 5-11 against COVID-19

 The Biden administration on Wednesday outlined its plan to vaccinate millions of U.S. children ages 5 to 11 as soon as the COVID-19 shot is authorized for them, readying doses and preparing locations ahead of the busy holiday season.

Unlike the mass vaccination centers used in the initial COVID-19 vaccine rollout, the White House said it is working to set up clinics in more than 100 children’s hospital systems nationwide as well as doctor’s offices, pharmacies and potentially schools.

If Pfizer Inc and BioNTech SE’s vaccine wins wider authorization from the U.S. Food and Drug Administration, the plan aims to ensure quick and equitable distribution, the White House said.

FDA officials are reviewing the Pfizer/BioNTech application seeking authorization of its 2-dose vaccine for younger children, with its panel of outside advisers scheduled to weigh in on Oct. 26. The FDA typically follows the advice of its panel but is not required to do so.

Advisers to the U.S. Centers for Disease Control and Prevention (CDC) will weigh in on recommendations for the vaccine at a meeting on Nov. 2 and Nov. 3, helping to inform a final decision by its director.

“Should the FDA and CDC authorize the vaccine, we will be ready to get shots in arms,” White House COVID response coordinator Jeff Zients told reporters, adding that the government had 15 million doses set to ship nationwide, with millions more going out in the weeks to follow.

Once authorized, roughly 28 million more children in the United States would be eligible to receive what would be the first U.S. COVID-19 vaccine for younger kids. The Pfizer/BioNTech shot is already available to those ages 12-17, and the companies are still studying it for children younger than 5.

Zients said the administration had worked with Pfizer to modify the packaging of the pediatric doses to make it easier to administer to children, including providing smaller needles.

While children have a lower rate of death from COVID-19, many face illness and long-term symptoms that are still being studied. Many adults who have been hesitant or opposed to the COVID-19 vaccine, and even some who did not oppose the vaccine for themselves, are expected to resist giving the shot to their children.

CDC Director Dr. Rochelle Walensky told reporters that the agency would continue to recommend mask wearing in schools even as the vaccine is rolled out for children.

Walensky said the seven-day average of COVID-19 cases in the United States was down about 16% to some 75,500 cases per day. The seven-day average for hospitalizations was down about 11% to around 6,000 per day, and that the seven-day average for daily deaths was down about 3% to 1,200.

https://www.amny.com/coronavirus/u-s-readies-plan-to-vaccinate-kids-ages-5-11-against-covid-19/

NYC to Mandate COVID-19 Vax For All Gov. Workers, Eliminate Weekly Testing Option

 Mayor Bill de Blasio announced on Wednesday that New York City will require all municipal workers—including first responders such as firefighters and police officers—to get at least one vaccine dose by October 29th. After that date, they will no longer be able to opt-out through weekly coronavirus testing.

As an incentive, city employees will have $500 added to their paychecks for receiving their first shot at a city-run vaccination site. Those who remain unvaccinated will be placed on unpaid leave until they show proof of inoculation to their supervisor.

“There is no greater privilege than serving the people of New York City, and that privilege comes with a responsibility to keep yourself and your community safe,” de Blasio said in a statement. “As we continue our recovery for all of us, city workers have been a daily inspiration. Now is the time for them to show their city the path out of this pandemic once and for all.”

The mayor said the order, which would be signed Wednesday by New York City Health Commissioner Dr. Dave Chokshi, would apply to approximately 160,500 city workers. That number does not include teachers and city healthcare employees, who are already required to get the vaccine. Of the remaining employees, about 71% have received at least one dose of COVID-19 vaccine.

The overall share of vaccinated employees has steadily climbed since the mayor first announced his "vax-or-test" rule in late July. The mayor's office said 83% of all municipal workers—roughly 305,000 people—had received at least one dose as of October 15th -- an increase of 18 percentage points. The size of the city's workforce fluctuates. When the mandates began to take hold in mid-August, there were around 367,000 city employees, but a spokesperson updated the figure Wednesday afternoon to 378,000.

But the city has struggled to convince certain groups, notably first responders, to get the shot. Only 69% of police officers have been vaccinated to date. The rate for city firefighters is even worse, that of 59%.

And amid surging coronavirus cases within the city's main jail complex on Rikers Island, only half of those working in the city's Department of Correction (DOC) have been immunized—the poorest vaccination rate of any city agency. Civilian DOC employees and its uniformed members working in healthcare settings must also immediately comply with the mandate. But to avoid adding to the DOC's staffing crisis, other uniformed members have more leeway, and their mandate doesn't take full effect until December 1st.

De Blasio's decision will likely draw protests from some municipal unions, which have sued over full vaccine mandates for teachers and health care workers. But those efforts have failed to overturn the policy. Early this month, Supreme Court Justice Sonia Sotomayor denied a request from a group of New York City teachers to prevent the mayor from implementing the mandate.

Nevertheless, Patrick Lynch, the president of the Police Benevolent Association, said a lawsuit was forthcoming from his police union. “Now that the city has moved to unilaterally impose a mandate, we will proceed with legal action to protect our members’ rights," he said.

At a news conference in Manhattan hours after the mayor's announcement, United Firefighters Association President Andrew Ansbro said the order immediately impacts more than 3,500 active duty first responders who are unvaccinated -- or 45% of FDNY’s total workforce. Ansbro warned that if these firefighters are sent home, it could lead to severe staff shortages at firehouses, which would then need to be temporarily closed.

“It's very hard to staff a firehouse as it is,” said Ansbro, who is vaccinated. “We'll definitely be closing firehouses if the amount of people that have told me they're not going to get vaccinated...if they get sent home, there's going to be a serious operational problem.”

Ansbro claimed that FDNY had reached herd immunity, given 55% of active duty firefighters have taken at least one dose of COVID-19 vaccine while over 70% of this workforce has recovered from the virus itself. He added those who’ve previously contracted COVID but have not been vaccinated should be exempt from receiving the vaccine. Public health experts disagree with this claim given immunity after a natural infection can be potent but on a much less consistent basis relative to vaccination.

Ansbro said the union will be exploring “all avenues” with other municipal unions to fight the mandate, keep the testing alternative and ensure that vaccination is "a personal choice."

But Henry Garrido, the head of District 37, the city's biggest municipal union, signaled their leadership was willing to negotiate with the city.

“We encourage all our members to get vaccinated to protect themselves and their families. The proposed mandate must be collectively bargained and we expect City Hall to slow down and sit down with us," Garrido said.

The city will begin bargaining immediately with unions over the mandate. Religious and medical exemptions will be permitted. But the mayor made it clear that those who fail to comply would face strong consequences.

"The bottom line is we're not going to pay people unless they're vaccinated. They'll lose their jobs," de Blasio said during a Wednesday interview on MSNBC.

New York City now joins a host of other cities, including Los Angeles and Seattle, that have issued strict vaccine mandates. Similarly, President Joe Biden has also required vaccinations for a majority of federal workers and contractors.

De Blasio, who is said to be mulling a run for New York governor next year, has tried to position the city as a national leader in the vaccination effort. His initial vax-or-test policy was held up as an example by President Biden. The move to impose a stricter mandate, which de Blasio had been hinting at for more than a month, comes with nine weeks to go in his mayoral term.

"We've got to end the COVID era," he told MSNBC. "Our police officers, our EMTs, our firefighters, all our public employees, a lot of them come in very close contact with their fellow New Yorkers. They need to be safe, their families need to be safe, but we also need to reassure all New Yorkers, that if you're working with a public employee, they're vaccinated."

During his morning press conference at City Hall, the mayor faced several questions about whether it was fair to give $500 to city employees who had held out on getting vaccinated when others went without such a benefit. All told, the payouts from the incentive program could cost the city as much as $23 million.

De Blasio argued that the city had taken incremental steps to convince more people to get vaccinated. He also noted the ongoing backdrop of "massive misinformation" around the vaccine.

"I'm coming from a very practical place to get us to a goal. And I think this is a smart incentive to help get us there," de Blasio said.

https://gothamist.com/news/nyc-will-mandate-covid-19-vaccines-all-government-workers

Tread Carefully in Choosing the Next FDA Leader

 Last week, a number of news outlets reported that Robert Califf, MD, may again be nominated to serve as FDA commissioner. Califf's prior term as FDA commissioner was brief; he was nominated during the final year of the Obama administration, serving from February 2016 to January 2017. During that time, he made one decision of monumental importance -- a decision that can be seen as the intellectual predecessor to recent drug approvals. As we consider Califf's potential nomination, let's revisit his previous tenure.

The Exondys 51 Controversy

In what feels like a lifetime ago -- 2016 -- we were in the midst of a different FDA debate. Eteplirsen (Exondys 51, Sarepta) was facing a regulatory decision by the FDA. The drug was intended to treat Duchenne muscular dystrophy, a grave and progressive condition for which there were limited and unsatisfactory treatment options.

The evidence supporting the drug was of very poor quality. We did not have a randomized controlled trial showing kids who get this drug lived longer or lived better. In fact, at the time of approval, the package insert noted specifically, "There was no significant difference in change in 6MWD [six minute walking distance] between patients treated with EXONDYS 51 and those treated with placebo." Instead, the drug was approved based on a change in dystrophin protein level, a surrogate endpoint of dubious value and uncertain correlation with living longer or better. Documents from within the FDA revealed considerable disagreement and turmoil about the approval.

Specifically, the drug advisory committee voted against approval, and FDA reviewers recommended rejecting the drug's application. Janet Woodcock, MD, director of the Center for Drug Evaluation and Research at the time, suggested the company perform additional biopsies to evaluate changes in the dystrophin protein, and authored an internal memorandum supporting the case for accelerated approval. This led agency director Ellis Unger, MD, to file a formal complaint of interference, and FDA's chief scientist Luciana Borio, MD, asked FDA Commissioner Califf to conduct a new scientific review of the product.

Califf wrote a memo deferring to Woodcock, an action that essentially granted the accelerated approval of this controversial treatment. With eteplirsen, Califf had a choice: he could trigger a re-evaluation of this product or he could accept the recommendation of Woodcock, ensuring approval. The former choice meant standing up for FDA reviewers, advisors, and scientific standards, and the latter would provide a financial boon to a drug company.

In deferring to Woodcock, Califf chose the latter, and the Los Angeles Times reported, "The effect on Sarepta's fortunes was immediate. The day the decision was announced, the company's share price soared from $28.15 to $48.94, a gain of 74%, and continued to rise until closing at a peak of $62.35 on Oct. 5." In November 2016, Nature Biotechnology summarized this affair and wrote, "doubts now surround standards for accelerated approval."

Accelerated approval of eteplirsen was not just a bad decision. It was the intellectual precedent needed for further erosion of FDA standards. We can even draw a line from the eteplirsen decision to recent controversies. In the last year, we witnessed the aducanumab (Aduhelm) decision for Alzheimer's disease. Here again, the FDA granted accelerated approval for a drug with no evidence people live longer or better, but on the basis of improving a disputed, uncertain biomarker. As I wrote in "The FDA is Failing the American People," the aducanumab decision was, once again, against the advice of an advisory panel vote.

Like a criminal empowered to push the envelope by getting away with past crimes, we likely would not have had aducanumab without eteplirsen. It set the precedent that these types of decisions are permissible and acceptable. The major difference is aducanumab will cost society many times more because of the larger patient population. And worse, with each approval of a new drug with limited evidence, we open the door for several more unjustifiable approvals down the road.

Where Does This Leave Us Today?

I wish to make two points about the potential re-appointment of Califf as FDA commissioner. First, I believe it is not only reasonable but necessary to judge a candidate for commissioner by past decisions on drug products or other regulatory matters. The eteplirsen decision was the first domino in a series that has led us to the present state of the agency when approving drugs that may cost society more than $100 billion without any idea if people are better off (aducanumab). This practice is unsustainable.

Second, in order to foster diverse and evolving thinking in leadership, choosing different people is a virtue. It is difficult to believe that there are so few scholars of regulatory science suitable for the position that we have to return to past holders. The challenge with repeat service as FDA commissioner is that former commissioners often accrue massive financial conflicts of interest, and their reappointment gives the appearance of corruption via a revolving door.

For more than a century, the FDA has set the standard globally. It defines what safe and effective therapies are, not only at home but across the world, and its imprimatur means something. Yet, the FDA has continued to lower its own standards, and approved products it would have quickly dismissed 25 years ago. The FDA stamp of approval now increasingly guarantees lofty pharmaceutical profits, but the U.S. public -- and the globe -- is getting increasingly suspicious. In this moment, the FDA has only one choice left: enforce a true efficacy standard or prepare for irrelevance. Only time will tell which choice we make.

Vinay Prasad, MD, MPH, is a hematologist-oncologist and associate professor of medicine at the University of California San Francisco, and author of Malignant: How Bad Policy and Bad Evidence Harm People With Cancer.

https://www.medpagetoday.com/opinion/vinay-prasad/95125

NYU surgeons successfully transplant kidney from genetically modified pig into human

 Surgeons at NYU Langone Health successfully connected a pig kidney to a human for the first time last month, USA Today first reported, paving the way for animal organs to become viable options for human transplant within the next few years.

The kidney, taken from a pig that was genetically modified by United Therapeutics subsidiary Revivicor, was attached to the blood vessels of a brain-dead patient on life support and kept outside the patient’s body for observation for a little over two days. Throughout that period, in a major first step for the realm of xenotransplantation, the human host didn’t immediately reject or experience any serious immune response to the organ.

The transplant recipient was a registered organ donor whose organs were found to be unsuitable for donation, according to The New York Times. The NYU team sought her family’s consent to instead perform the experimental xenotransplant before she was taken off life support.

Not only did the kidney proceed to filter waste and produce urine at normal rates, it also returned the patient’s abnormal creatinine level—caused by poor kidney function—to normal levels.

“It was better than I think we even expected,” Robert Montgomery, M.D., the NYU transplant surgeon who led the procedure, told the NYT. “It just looked like any transplant I’ve ever done from a living donor. A lot of kidneys from deceased people don’t work right away and take days or weeks to start. This worked immediately.”

The pig’s genes had been edited to remove a sugar molecule from its tissues that has been linked to organ rejection in previous xenotransplants.

Revivicor earned the FDA’s approval last December for its genetically modified GalSafe pigs, which are named after the alpha-gal molecule that’s edited out of their genes. The approval covered Revivicor’s intentional genomic alteration, allowing the pigs to ultimately be used to create human food that wouldn’t trigger allergies as well as for biomedical products like donor organs—though any proposed medical uses for the GalSafe pigs will need additional individual FDA approvals.

The results of the procedure at NYU Langone have yet to be published in a peer-reviewed study, and the patient was only observed for a total of 54 hours after the kidney transplant, but the reported results are certainly promising for the more than 106,000 people currently waiting for donor organs and the physicians and scientists who have long been on the hunt for an effective and sustainable alternative to human donations.

Revivicor isn’t the only one looking to our porcine pals to solve some of medicine’s biggest challenges. In late 2019, the FDA gave XenoTherapeutics the go-ahead to begin a clinical trial to study whether live skin cells derived from genetically engineered pigs could be used to treat severe burns in humans.

Startups including Miromatrix and eGenesis have also attracted millions for their own efforts to develop gene-edited pigs for use as organ donors. The latter closed an impressive $100 million funding round in 2019, then outdid itself earlier this year with a $125 million series C. Miromatrix, meanwhile, opted to go the public route, reeling in an upsized $43 million IPO in June.

https://www.fiercebiotech.com/medtech/nyu-surgeons-successfully-transplant-kidney-from-genetically-modified-pig-into-human

Entasis finds success in resistance

 The paucity of new antibiotics, and particularly of those for drug-resistant strains of bacteria, could bode well for Entasis Therapeutics when it comes to filing its lead project. In the phase 3 Attack trial sulbactam-durlobactam (Sul-Dur) showed noninferiority against the marketed antibiotic colistin in patients with infections caused by Acinetobacter baumannii. The combination also showed a numerical survival benefit: at 28 days all-cause mortality with Sul-Dur was 19% compared with 32% in the colistin arm. Acinetobacter baumannii has shown high rates of drug resistance, and is responsible for a number of hospital-acquired infections, so it is almost certain that there will be regulatory interest in the project. Entasis plans on filing by the start of 2022. There is, however, still a way to go before approval, and sales of antibiotics can be tricky to model as new products tend to be reserved for use as a last resort. This could explain why Entasis’s shares climbed just 3% this morning. Should Entasis get FDA approval this could be another example of Astrazeneca’s successful policy of spinning out non-core assets, following the buyout of Viela Bio and approval of Albireo Pharma's Bylvay this year.

Source company presentation

https://www.evaluate.com/vantage/articles/news/snippets/entasis-finds-success-resistance