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Friday, February 4, 2022

FDA Concerned About Safety of Lymphoma Drug

 The FDA has begun an investigation into the safety of the lymphoma drug umbralisib (Ukoniq) after preliminary data from a clinical trial suggested an increased mortality risk in patients treated with the PI3K inhibitor.

The potential adverse safety signal arose from the phase III UNITY-CLL trial comparing umbralisib plus the anti-CD20 antibody ublituximab versus obinutuzumab (Gazyva) plus chlorambucil for chronic lymphocytic leukemia. Umbralisib currently has approved indications for relapsed/refractory marginal zone lymphoma and follicular lymphoma.

"Because of the seriousness of this safety concern and the similarities between the two types of cancer for which this drug is approved and the type of cancer that was studied in the clinical trial, we are alerting patients and healthcare professionals that we are re-evaluating this risk against the benefits of Ukoniq for its approved uses," noted an FDA Drug Safety Communication.

The FDA Oncologic Drugs Advisory Committee (ODAC) may also convene to consider the findings of the safety evaluation and "explore" the continued marketing of umbralisib. Additionally, the agency has halted enrollment in other ongoing clinical trials of umbralisib during the review of the UNITY-CLL data, according to the safety communication.

Late last year, umbralisib sponsor TG Therapeutics issued a statement acknowledging that the FDA plans to convene ODAC to consider the UNITY-CLL data within the context of the ongoing review of the company's application for approval of the umbralisib/ublituximab (U2) combination.

"We believe Ukoniq is a unique PI3K inhibitor, with a differentiated toxicity and tolerability profile and believe the data submitted thus far are supportive of approval of U2 in CLL," said Michael S. Weiss, CEO of TG Therapeutics.

Overall survival (OS) is a secondary endpoint of the UNITY-CLL trial. According to TG Therapeutics, the FDA requested an early OS assessment, which showed the U2 arm had a 23% higher mortality, a difference that did not achieve statistical significance. After excluding deaths associated with COVID-19, the survival hazard with U2 decreased to 4%, essentially the same as in the control arm.

"The overall survival results are preliminary, and the company will continue to evaluate the endpoint over time as more events are evaluable and will continue to analyze how COVID-19 may be impacting the analysis," the statement continued.

Although ODAC has yet to announce a date for the umbralisib review, the FDA indicated that the meeting would occur in March or April, according to TG Therapeutics.

https://www.medpagetoday.com/hematologyoncology/lymphoma/97003

Many Adults Who Thought They Had COVID-19 Actually Didn't

 About half of unvaccinated adults who thought they had COVID-19 were proven wrong by antibody tests, researchers found.

In a survey of people recruited on social media, 45% of people who thought they'd had COVID, but never confirmed it, actually had no anti-spike antibodies, reported Dorry Segev, MD, PhD, of Johns Hopkins University in Baltimore, and colleagues, in a JAMA research letter.

Overall, antibodies were detected in 99% of people who said they had a positive COVID-19 test result, in 55% who believed they had COVID-19 but who were never tested, and in 11% who thought they never had SARS-CoV-2 infection.

The study took place before the Omicron wave, in which all forms of immunity have shown to be less durable. Other limitations noted by the authors included a lack of direct neutralization assays, as "antibodies alone do not directly equate to immunity," they wrote.

Segev and co-authors recruited healthy unvaccinated adults through a Twitter post and a Facebook ad from Sept. 11, 2021 to Oct. 8, 2021. Participants answered a questionnaire about demographics, COVID status, and mask use. They were divided into three groups:

  • COVID-confirmed: people who reported a test-confirmed COVID infection
  • COVID-unconfirmed: people who believed they had COVID, but were never tested
  • No-COVID: people who did not believe they had COVID and never tested positive

All groups were invited to undergo antibody testing. Overall, 816 adults underwent screening and filled out the questionnaire. Respondents had a mean age of 48, 52% were women, and 82% were white.

The COVID-confirmed group had 295 participants; of these, antibody testing confirmed 99% actually had COVID. A median of 8.7 months (range 0-20) had passed since this group's self-reported COVID diagnosis. The median level of antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD) among those who tested positive was 205 U/mL, and "levels did not differ by months since diagnosis," according to the researchers.

Among 275 people in the COVID-unconfirmed group, the median anti-RBD level among those who tested positive was 131 U/mL. Of 246 people in the no-COVID group, the median anti-RBD level among those who tested positive was 82 U/mL.

Segev's group acknowledged that COVID diagnoses were self-reported in this study, and there may be "an unknown degree of selection bias" due to the survey's public recruitment efforts. In addition, the study population was healthy and mostly white, which could limit its generalizability.


Disclosures

This study was supported by the Ben-Dov family.

Segev disclosed support from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, Thermo Fisher Scientific, AstraZeneca, Regeneron, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and NIAID.

Other co-authors disclosed support from the American Society of Transplant Surgeons and NIDDK.

Medicare 'hemorrhaging money on scams and fraud': Warren

 The Medicare program could easily become solvent if regulators cracked down harder on fraudsters and profiteers, Sen. Elizabeth Warren (D-Mass.), chair of the Senate Finance Subcommittee on Fiscal Responsibility and Economic Growth, said Wednesday.

"The Medicare system is hemorrhaging money on scams and fraud," Warren said at a hearing on Medicare financing. "It is critical that we stop the flow and if we do, the system will have more than enough money to operate at its current level and increase coverage."

Concerns About Drug Prices

Pharmaceutical companies were one target of Warren's ire. "In 2019, total Medicare spending on prescription drugs was $220 billion," she said. "Because Medicare cannot negotiate prices, drug companies are able to rake in billions in profits. Now that's bad enough, but the drug companies have more ways to juice their profits: they use anti-competitive tactics like 'pay for delay,' product hopping, and patent thickening, all while anti-trust regulators turn a blind eye. It's enough to gag a maggot."

She also pointed to the private insurers who participate in Medicare Advantage. "Medicare Advantage was ... built on vague promises of cost savings, but instead, it has cost Medicare almost $150 billion extra over the past 12 years," Warren said. "Because greedy private insurers are gaining the program's rules, including its risk adjustment process, its benchmark policy, and its quality bonus program, all to squeeze more money out of Medicare and to drive up the costs for taxpayers."

Making changes to both those programs could save more than $900 billion over 10 years, while the estimated shortfall in Medicare's hospital insurance trust fund is $517 billion between 2026 and 2031, and the cost of extending Medicare coverage to include dental, vision, and hearing benefits is just under $360 billion. "In other words, we don't need to cut Medicare benefits. We need to cut out the scams that are bringing Medicare down," she said.

Arguments Against Expanding Medicare Benefits

Sen. Bill Cassidy, MD (R-La.), the subcommittee's ranking member, had different ideas. Expanding Medicare benefits "doesn't make sense to me," he said. "We have an obligation to the people currently being covered, and yet we will expand the benefit and maybe have insolvency come even quicker." Cassidy noted that if Medicare were to become insolvent, "under current law, it would be an immediate cut to providers of roughly 20% to 30%," something that providers would not be able to afford, leading to less provider access for beneficiaries.

Although some people have suggested doing away with beneficiary cost-sharing, "there's a lot of data showing that one thing that puts the brakes on it is if you have just a little bit of cost-sharing, Cassidy said. "Not too much so the diabetic does not get her needed care, but at least a little bit so people think twice."

"It's time to take a modern approach to the way we deliver healthcare," using an approach "that rewards providers for keeping patients out of hospital beds and one that recognizes the patient, and the doctor, and that relationship as the ultimate arbiter of value, health, and well-being," he continued. "We can get there without disrupting the quality and access our constituents need, but the discussion has to begin today."

Hearing witness James Capretta, senior fellow at the American Enterprise Institute, a right-leaning think tank here, suggested five ways to modernize the program: putting the Medicare benefit together into one understandable, coordinated benefit with rational cost-sharing; making the choices between various Medicare plans more understandable for patients; strengthening premium competition among the available options; improving price competition among providers; and consolidating the various Medicare trust funds, so the financing of the entire program would be more clear.

Amy Kapczynski, JD, faculty co-director of the Law and Political Economy Project at Yale Law School in New Haven, Connecticut, noted that current drug pricing doesn't accurately reflect companies' research and development costs. She had several suggestions for improving Medicare drug coverage. In addition to allowing Medicare to negotiate drug prices, "we should also have legislation that penalizes price spikes to prevent price gouging on existing drugs," she said. "We should explore legislation to curb anti-competitive patent-thickening, and [legislation] that would strengthen rules against 'pay for delay' settlement deals. And we should also critically provide the [Federal Trade Commission] with more resources and authority to address anti-competitive conduct in the sector."

Direct Contracting in the Spotlight

A Medicare demonstration program known as Direct Contracting came under some criticism at the hearing. Under the program, accountable care organizations (ACOs), insurance companies, and health systems, would agree to provide care for a certain number of traditional Medicare beneficiaries in a geographic area for a set amount of money.

"CMS has invited the same insurers that are already scamming Medicare and dozens of new investor-owned organizations to cover traditional Medicare beneficiaries through a new privatized Direct Contracting model that lets them pocket -- get this -- as much as 40% in profits," Warren said. "This invites fiscal disaster, and I hope this administration will reverse this decision."

Susan Rogers, MD, president of Physicians for a National Health Program, a lobbying group for single-payer healthcare that has protested against Direct Contracting, agreed. "We cannot let Medicare become a playground for Wall Street investors," Rogers said. "We need to get back to what we know works, and that's traditional Medicare."

On the other hand, Katherine Baicker, PhD, professor of public policy at the University of Chicago, spoke in favor of more use of alternative payment models in Medicare, including ACOs. "Right now, Medicare's fee-for-service traditional structure gets the prices wrong, despite all best efforts," she said. "It's very difficult to write down prices that align with value on a line-by-line basis. And we see overuse of some services at the same time that we see underuse of other services. And that's not the best way to ensure we get the most health for beneficiaries for every dollar that we spend."

Instead, "reforms that align payments to providers with the value of healthcare that the service provides could help our dollars go further in promoting health and well-being for beneficiaries," Baicker said. "That would include some alternative payment models, each of which has challenges but has potential. We've seen experiments in the Medicare program with alternative payment models like bundled payments or capitated payments or ACOs ... Some of the experiments in bundled payments, particularly those looking at joint replacement, have seen reduction in costs while maintaining the quality of outcome for beneficiaries."

https://www.medpagetoday.com/publichealthpolicy/medicare/97016

Biogen's Aduhelm marketing, approval under fire in new FTC and SEC probes

 When it comes to the Alzheimer’s disease med Aduhelm, Biogen can’t seem to catch a break. Alongside meager sales and a stifling Medicare coverage proposal, the drug is now bound for more scrutiny under a pair of U.S. government probes.

The Federal Trade Commission (FTC) and the Securities and Exchange Commission (SEC) have launched two separate investigations into Biogen and its troubled Alzheimer’s med, the company revealed in an annual securities filing Thursday.

The FTC has made a civil investigative demand—a type of administrative subpoena—in pursuit of documents related to Aduhelm’s marketing and approval, plus healthcare sites, the company said.

The SEC, meanwhile, has launched a separate inquiry that also seeks marketing and approval information on the beleaguered anti-amyloid antibody.

Biogen won accelerated approval for Aduhelm last summer, but the FDA based its decision on a surrogate endpoint—the removal of amyloid plaques—rather than slowing cognitive decline. The FDA’s decision also went in the face of a resounding ‘no’ from the advisory committee that met on Aduhelm’s approval.

This isn’t the first Aduhelm investigation, either. In June, the House Committee on Oversight and Reform said it was launching a probe into the drug’s controversial approval and pricing. Biogen originally priced the drug at $56,000, but eventually slashed the cost to $28,200 for a patient of average weight.

The lawmakers have also asked the FDA to produce additional data and documentation supporting its accelerated approval for the drug. The FDA, meanwhile, is conducting its own investigation into the drug, Endpoints notes. 

Aduhelm’s rocky rollout has translated into poor sales, too. The drug made just $1 million for the fourth quarter and $3 million for all of 2021, Biogen reported Thursday. That pales in comparison to the hundreds of millions of dollars in selling, general and administrative expenses the company has recorded on the beleaguered medicine so far.

https://www.fiercepharma.com/pharma/biogen-s-aduhelm-marketing-approval-under-fire-new-ftc-and-sec-probes

Britain’s pandemic modellers say future large waves of COVID possible

 There is a realistic possibility of large waves of COVID-19 infection in the future in Britain and such waves might even be considered likely, epidemiologists who model the COVID-19 pandemic to inform government advice have said.

“Large future waves of infection that need active management to prevent detrimental pressure on the health and care sector are, at least, a realistic possibility (high confidence) or likely (medium confidence),” the Scientific Pandemic Influenza Group on Modelling, Operational sub-group (SPI-M-O) said in a consensus statement published on Friday.

https://kfgo.com/2022/02/04/britains-pandemic-modellers-say-future-large-waves-of-covid-possible/

Record Number of Americans Missed Work Due to Illness in January

 A record number of people, totaling more than 3.6 million, were unable to work due to illness during the week that officials gathered data for the benchmark U.S. monthly employment report, which coincided with the peak in infections from COVID-19.

Labor Department data released on Friday showed that figure was up from nearly 1.7 million in December. The survey for January's report was conducted during the week of Jan. 9-15, the week that infections driven by the highly infectious Omicron variant peaked in the United States. The data on absences from illness dates to 1976.

https://www.usnews.com/news/us/articles/2022-02-04/record-number-of-americans-missed-work-due-to-illness-in-january

FDA Suddenly Scrubs Moderna Document From Website After Reporters Ask Questions

 by Zachary Stieber via The Epoch Times (emphasis ours)

A Food and Drug Administration (FDA) document explaining why the agency approved Moderna’s COVID-19 vaccine was removed from the agency’s website overnight.

The Summary Basis for Regulatory Action offered more details about how regulators reached the approval decision, and included references to an unpublished analysis that found the rates of post-vaccination heart inflammation were higher than any U.S. agency had found before.

After The Epoch Times reviewed the document and sent questions about it to FDA spokespersons, it disappeared from the agency’s website.

We are aware of the issue and hope to have the document reposted as soon as possible,” a spokesperson told The Epoch Times in an email on Feb. 3.

Reached by phone and asked for more details about the issue, the spokesperson said: “I reached out to the website people. I don’t really have any more information to tell you.”

The Epoch Times has submitted Freedom of Information Act requests for the document and several unpublished analyses referenced in it, including the FDA meta-analysis.

Barbara Loe Fisher, president of the National Vaccine Information Center, a nonprofit that advocates for informed consent, told The Epoch Times in an email that “the public has the right to review the evidence FDA is using to license new mRNA vaccines as safe and effective.”

“Lack of transparency only fosters distrust in government agencies charged with protecting the public health. FDA should immediately release all information related to the incidence of myocarditis and other serious adverse events following mRNA COVID-19 vaccinations, whether that information has been provided to the agency by vaccine manufacturers or discovered through in-house analyses of additional data collected by federal officials,” she wrote.

The FDA meta-analysis examined data of four health care claims databases and estimated that, among males aged 18 to 25, the rate of myocarditis following Moderna’s primary series was 148 per million males vaccinated.

That figure is higher than other government estimates, including a Centers for Disease Control and Prevention (CDC) analysis of reports submitted to the Vaccine Adverse Event Reporting System. The analysis found about 10.7 cases per million males aged 18 to 24 who got Moderna’s first shot and 56 cases per million among those who received Moderna’s second shot.

Myocarditis is one type of heart inflammation that people who receive vaccines built on messenger RNA (mRNA) have experienced at higher-than-expected rates. It also occurs among people who contract the CCP (Chinese Communist Party) virus, which causes COVID-19.

Moderna’s shot, a type of mRNA vaccine, is administered in a two-dose primary series. The doses are administered about a month apart.

The FDA approved Moderna’s vaccine on Jan. 31 without convening its expert vaccine advisory panel, a growing trend for the agency.

The CDC’s vaccine advisory committee is scheduled to meet on Feb. 4 to review data on the jab.

An agenda (pdf) for the meeting says a Moderna scientist will present safety and efficacy data on the company’s shot, followed by CDC researchers discussing updates on post-vaccination heart inflammation and the benefit-risk framework in light of the most recent analyzed information.

Researchers in the UK found in December 2021 that men under 40 were much more likely, and females under 40 were more likely, to suffer from heart inflammation after Moderna’s second shot than from COVID-19 itself.

https://www.zerohedge.com/covid-19/fda-suddenly-scrubs-moderna-document-website-after-reporters-ask-questions