ACC 2022 – Bristol's rare hit could justify Myokardia

 Bristol Myers Squibb paid $13bn for mavacamten’s developer, Myokardia, so it needs the project to be a hit. Today the company got a boost with impressive results from Valor-HCM study, in a sicker population of hypertrophic cardiomyopathy patients than the one in which the asset had previously been tested.

Bristol looks like it will have its work cut out to hit the $4bn-plus peak sales target it has set for mavacamten but, as with many rare diseases, the group hopes that having a therapy available will spur more patients to be diagnosed.

Amyloidosis on steroids

Valor’s lead investigator, Dr Milind Desai of the Cleveland Clinic, told Evaluate Vantage on the sidelines of the ACC meeting that in terms of market size hypertrophic cardiomyopathy (HCM) was "amyloidosis on steroids". 

Amyloidosis, of course, is a disorder that has proven a nice little earner for the likes of Pfizer and Alnylam.

HCM involves excessive contraction and progressive thickening of the heart muscle tissue, and can lead to heart failure and sudden cardiac death. There are no specific therapies approved.

Bristol is initially targeting the disorder's obstructive form, which involves blockage of the left ventricular outflow tract, where blood leaves the heart, and affects around two thirds of patients.

Here, mavacamten has a Pdufa date of April 28, based on data from the Explorer-HCM study (ESC 2020 – Myokardia odds-on for first approval in heart muscle disease, August 29, 2020).

Valor focused on a sicker group of patients than Explorer: those with severely symptomatic obstructive HCM who were candidates for septal reduction therapy, a procedure to reduce the thickness of the heart tissue that comes with its own risk of death.

Patients were randomised to either mavacamten or placebo, and continued on background therapy including disopyramide and beta blockers. At any time during the trial patients could opt for septal reduction.

The primary endpoint of Valor was the proportion of patients who had either decided to have the procedure, or were still eligible, at week 16. Only 18% of mavacamten-treated patients fell into these groups, versus 77% of those receiving placebo.

The study also hit all of its secondary endpoints.

Valor results at ACC 2022
Endpoint	Mavacamten	Placebo	P value
Proportion of pts who had or were eligible for SRT*	18%	77%	<0.0001
Change in post-exercise LVOT gradient	-39.1mmHg	-1.8mmHg	?
No. of pts with ≥1 class NYHA improvement	63%	21%	<0.0001
Change in KCCQ-23 clinical summary score	+10.4 points	+1.9 points	<0.0001
*Primary endpoint; KCCQ=Kansas City cardiomyopathy questionnaire; LVOT=left ventricular outflow tract; NYHA=New York Heart Association. Source: ACC 2022.

As for safety, Valor did not throw up any new issues. As mavacamten, a cardiac myosin inhibitor, is designed to reduce the hypercontractility seen in HCM, there are concerns that the project could cause dangerously low ejection fractions.

Dr Desai explained that the “hard stop” in Valor was an LVEF of 30% or below, and highlighted that no patient met this criterion. However, two patients had LVEF that dropped below 50% – these subjects briefly stopped taking mavacamten, their ejection fractions recovered, and they subsequently resumed treatment on a lower dose.

Bristol plans to address these concerns with a risk-evaluation mitigation strategy (REMS), and it was updates to this that caused an FDA decision on mavacamten to be pushed back from the original target of November.

“The REMS was always something we’d planned for given the mechanism of action of the drug,” Marie-Laure Papi, the development lead for mavacamten at Bristol, told Vantage.

In Valor, echocardiogram measures were used to help titrate the dose of mavacamten to individual patients. It should soon become clear whether this strategy will be enough for the FDA.

HFpEF plans

Assuming it is, and mavacamten becomes the first approved therapy for HCM, Bristol is not stopping there. The group plans to start a phase 3 study in non-obstructive HCM this year, and the project is in phase 2 in heart failure with preserved ejection fraction, another cardiac disorder that until recently has had few options.

The competition is some way behind: Cytokinetics recently started the phase 3 Sequoia-HCM trial of its rival cardiac myosin inhibitor aficamten (CK-274), while a couple of projects are in phase 2 for non-obstructive disease.

Dr Desai reckons that the 100,000 patients who are currently diagnosed with HCM in the US is the “tip of the iceberg”. If he is right there should be room for more than one player in this market.

Projects in development for hypertrophic cardiomyopathy
Project	Company	Description	Trial
Filed
Mavacamten	Bristol Myers Squibb	Cardiac myosin inhibitor	Pdufa April 2022 based on Explorer-HCM
Phase 3
Aficamten	Cytokinetics	Cardiac myosin inhibitor	Sequoia-HCM in obstructive HCM completes Sep 2023
Phase 2
IMB-101	Imbria Pharmaceuticals	Partial fatty acid oxidation inhibitor	Improve-HCM in non-obstructive HCM completes Nov 2022
Entresto	Novartis	Angiotensin receptor-neprilysin inhibitor	NCT04164732 in non-obstructive HCM completes May 2023
Cufence (trientine dihydrochloride)	Univar Solutions	Copper chelating agent	Tempest completes Dec 2023*
Phase 1
CT-G20	Celltrion	Cardiac myosin inhibitor	NCT04418297 in obstructive HCM completes Apr 2022
MYK-224	Bristol Myers Squibb	Cardiac myosin inhibitor	NCT05304533 completes Sep 2022
*Investigator-sponsored trial. Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/events/conferences/acc-2022-bristols-rare-hit-could-justify-myokardia

8 reasons why health care cost inflation is likely to escalate

 Health care costs in the U.S. decreased for the first time in our lifetimes due to decreases in elective, preventive, and chronic disease care caused by the pandemic. By 2021, however, health care costs caught up to pre-pandemic projections. Eight factors, outlined below, indicate a return to health care cost increases far above inflation, posing enormous challenges to employers and health plan sponsors.

1.  Provider costs have genuinely increased. 

Hospitals and providers are not impervious to general inflationary trends. Providers face increased costs for fuel and medical supplies and will seek to pass on these costs. The “Great Resignation” has not spared health care. Hospitals also face staffing shortages, and agency and “travel” nurse expenses have soared. These increases raise the cost basis for medical care and will increase health care inflation in coming years.

2.  Providers will have more leverage at the contracting table due to provider consolidation and public sympathy.

Weaker hospital systems and providers were more likely to fail during the pandemic, and their volume is likely to have been absorbed by stronger systems that enjoy more negotiating leverage and higher reimbursement rates.

Many health plan contracts with health systems are three or more years long, so these increases could extend through or beyond 2025.

Providers saved countless lives during the pandemic, and doctors, nurses and others practiced at great personal risk in excruciating conditions with crippling shortages of personal protective equipment. Health plans will have a harder time in the court of public opinion during contractual disputes, making them more likely to accede to provider financial demands.

3.  The cost of drugs will continue to rise.

There’s also been no slowdown in the rise of drug prices during the pandemic, and the federal government has failed to pass any meaningful legislation to control drug prices.

There is widespread public support for regulations to address the high cost of drugs in the U.S. compared to other developed countries, but little agreement among legislators about what action to take.

The pandemic led to a slowdown in research and approvals for new drugs not aimed at coronavirus. As the pandemic recedes, there will be an increase in the number of new and expensive personalized drugs.

4.  Preventive care, chronic disease management, and non-emergent surgeries were delayed or foregone during the pandemic.

Mammography and colonoscopy screenings fell dramatically during Spring 2020, and cancer screening rates have not yet recovered. Decreased cancer screening lowered medical costs during the pandemic but could raise future costs as more patients are diagnosed with later stage, high-cost cancers in subsequent years. For example, UC Davis has already reported a four-fold increase in diagnosis of Stage IV breast cancer.

Childhood immunization saves lives and costs by preventing epidemics like measles, but pediatric vaccinations were down 42 percent in Spring 2020. While vaccination of preadolescents has rebounded, adolescent vaccination continues to lag without a compensatory bump to make up for vaccinations missed in the first year of the pandemic. Childhood vaccines save thousands of lives and billions of dollars; fewer children fully immunized will increase health care costs as well as lead to preventable illness and death.

Some patients delayed or avoided medical care for chronic conditions like heart disease or diabetes, and we might face higher costs from complications including end stage renal disease and congestive heart failure due to more advanced disease in subsequent years. Some patients will never get the non-emergency procedures they missed during the pandemic, but many delayed surgeries and other procedures will be scheduled in the future. Some of these, including operations for cancer and orthopedic disease, could be more complicated than originally planned.

5.  Costs of long-term complications of COVID-19 could be large.

As many as one in six who have recovered from COVID-19 continue to have symptoms six months later.

Researchers also found that incidence of heart attack, stroke and congestive heart failure soared after recovery from COVID-19. Even mild cases of COVID-19 can lead to lasting damage to small airways. Researchers have also identified cognitive decline and changes in brain anatomy associated with COVID-19.

There are ten drugs now under investigation to treat Long COVID; these could improve quality of life and decrease disability but are likely to be costly.

6.  The pandemic has worsened mental health.

Three times as many Americans report severe symptoms of anxiety and depression compared to before the pandemic, and drug overdose deaths are at their highest level in history.

Access to mental health care was poor even before the pandemic, and many continue to be unable to get necessary mental health care despite the dramatic increase in virtual care. Untreated mental illness is associated with substantial preventable medical costs, and the emotional trauma from an event with widespread death can last for years.

7.  Government programs that have funded vaccinations and treatments for COVID-19 will expire this year.

The federal government has purchased all COVID-19 vaccinations, monoclonal antibodies, and doses of oral medication for COVID-19 since the beginning of the pandemic. But funds to pay for these products are fast running out, and billions in funds for vaccines and therapeutics requested by the Biden administration face an uncertain future in Congress.

We often don’t know what price the government is paying for these products, but the unit cost paid by private insurance plans is likely to be higher, and employer-sponsored health plans are paying only administration costs for vaccinations and COVID-19 drugs now.

8.  The end of the pandemic emergency will decrease Medicaid enrollment and enhanced subsidies for exchange plans are set to end.

State Medicaid agencies have been prohibited from disenrolling Medicaid beneficiaries during the pandemic, but millions could lose their Medicaid benefits when the pandemic emergency is over.

Federal subsidies for those purchasing individual insurance on the exchanges will also decrease at the end of 2022 unless new legislation is passed.

Some employees or their family members who have remained on Medicaid or exchange plans and waived employer sponsored health insurance during the pandemic could seek coverage from employers. We will likely see an increase in those who are uninsured, which will place additional pressure to shift costs to commercial health plans.

All this points to a return to extreme annual health care inflation which will pose challenges to employers and other plan sponsors. Government will also feel pressure from rising health care costs, as it provides health insurance for government employees, senior citizens, the poor and disabled, and subsidizes insurance for many in the individual market. At a time when wages are increasing, health care inflation further increases total labor costs, increasing the likelihood that companies will pursue automation or offshoring.

Employers have responded to health care cost increases in the past by shifting costs to members, which lowers plan sponsor costs but exacerbates health care affordability concerns at a time when many families are already having trouble paying for health care. Employees are increasingly willing to consider leaving their current employer, making further cost shifting an undesirable approach. 

In response, employers will use formularies to manage drug costs and steer members to lower cost providers to manage medical costs. Additionally, they’ll look to better coordinate care of the 5 percent of members with serious illness who account for roughly half of total health care costs. Employers likely will continue to increase access and engagement in mental health services. Alternative payment models such as bundled payment and capitation can lower total cost by lowering utilization. Restrictions on site of service can decrease total costs by directing patients to lower cost settings. Other options include value-based contracting and value-based insurance design that can increase uptake of high-value care and decrease utilization of low-value care.

Overall, employers and other health plan sponsors will need to return to steady vigilance and proactive strategies and programs that allow them to prepare for substantial increases in health care costs coming over the coming years.

Jeff Levin-Scherz, M.D., MBA. is an assistant professor at the Harvard T.H. Chan School of Public Health and a managing director and population health leader of the North American Health and Benefits Practice at Willis Towers Watson

https://thehill.com/opinion/healthcare/3257431-8-reasons-why-health-care-cost-inflation-is-likely-to-escalate/

Obama, Hunter Biden ties to Ukraine biolabs get fresh scrutiny

 In August 2005, the U.S. entered into a little known agreement with Ukraine that included America aid to upgrade security at Ukrainian facilities in which microbes were kept.

Now, almost 17 years later, questions about the deal – and the United States' broader support for biodefense laboratories in Ukraine – have surfaced amid concerns about chemical or biological weapons being used in Russia's invasion of Ukraine.

The Russian government has been claiming for weeks that the U.S. government is funding bioweapon labs in Ukraine, justifying its invasion as an effort to stop a joint American-Ukrainian plan to wage biological warfare against Russia.

Chinese officials and state media have echoed the claims, which Andrew Weber, senior fellow at the Council on Strategic Risks, calls "utter nonsense." 

"It's KGB-style misinformation that's been going on for about 15 years," he said Monday.

One concern among analysts and U.S. officials is that Russia could be laying the groundwork for using chemical or biological weapons in Ukraine and giving itself plausible deniability by blaming Ukrainian labs.

Experts and U.S. officials agree with Weber that Moscow's accusations are unfounded, roundly dismissing them as propaganda.

"Russia is inventing false pretexts in an attempt to justify its own horrific actions in Ukraine," State Department spokesperson Ned Price said earlier this month.

Others have pointed out that no evidence exists to show Ukraine is working to produce weapons of mass destruction.

Director of National Intelligence Avril Haines testified earlier this month that "we do not assess that Ukraine is pursuing either biological weapons or nuclear weapons."

United Nations High Representative for Disarmament Affairs Izumi Nakamitsu similarly said the international group is "not aware" of any biological weapons program in Ukraine.

The U.S. and Ukraine are members of the Biological Weapons Convention, which prohibits such weapons. And the U.S. government has said both countries are in full compliance.

Russia, however, is not in compliance and "maintains an offensive biological weapons program," according to the State Department.

Weber told Just the News the Russian government has three top-secret military laboratories conducting work on biological weapons that have never been visited or observed by outside inspectors.

"It's very disingenuous for Russia to point its finger at the U.S. and Ukraine," he said. "Both Russia and China know there's nothing untoward going on there."

Weber was the Pentagon official in charge of the U.S.-funded program that worked with the Ukrainian government and spearheaded negotiations with Kyiv on securing biological material.

After 9/11 and subsequent anthrax attacks across the U.S., Weber explained, the president of Ukraine asked Washington to assess the security of his country's chemical and biological labs. The U.S. and Ukraine each wanted to counter the threat of bioterrorism and to prevent the proliferation of biological weapons, materials and technology, he also said.

Weber led a team that identified a number of labs run by Ukraine's Ministry of Health that would be good partners for the effort – many of them in poor shape with dangerous pathogen collections left over from the Soviet Union.

While Ukraine's labs weren't directly involved in the Soviet biological-weapons program, some of their pathogens were used for Moscow's weaponization work.

After months of negotiations, the Pentagon and the Ukrainian ministry in August 2005 struck an agreement under which the U.S. agreed to send aid to Ukraine to fund security upgrades at Ukrainian facilities in which pathogens were stored and to support Ukrainian research on fighting the spread of diseases. 

The purpose was purportedly to consolidate pathogen collections into one or two safer and more secure labs in Ukraine and to strengthen Ukraine's public health capacity to respond to disease outbreaks.

Today, with the Russia invasion roughly one-month long, there are concerns that Russia could either capture Ukraine's biolabs for their own purposes or strike them and accidentally release stored pathogens.

Such concerns have prompted the World Health Organization to urge Ukrainian authorities to destroy research samples of disease pathogens in their labs.

The 2005 agreement extended to Ukraine the Cooperative Threat Reduction Program, which was established in 1991 to secure and dismantle weapons of mass destruction and their associated infrastructure in the former states of the Soviet Union. The program is housed within the Defense Department's Defense Threat Reduction Agency.

The program has spent about $12 billion on securing material used in weapons of mass destruction in post-Soviet republics, according to the DTRA. Roughly $200 million of that total has been spent on supporting 46 Ukrainian laboratories, health facilities and diagnostic sites.

There may have been some U.S. funding to support Ukrainian biodefense labs before 2005, but it would have been small and through the Science and Technology Center in Ukraine, Weber also said.

The final deal, which was meant to defend against bioweapons rather than build them, was announced by then-Sens. Richard G. Lugar, an Indiana Republican, and Barack Obama, an Illinois Democrat, during a visit to Kyiv, the Ukrainian capital.

For the last nearly two decades, the deal been the basis for U.S.-Ukraine collaboration on biological materials.

"That's been the legal framework" ever since, said Weber. "It's been a successful collaboration," despite Russian claims to the contrary.

However, one recent assertion by Russia appears to be at least partially true: that President Biden's eldest son, Hunter Biden, helped finance biolab projects in Ukraine.

Hunter Biden and his colleagues invested $500,000 in a Pentagon contractor through their firm, Rosemont Seneca Technology Partners, and raised millions more through other firms that included Goldman Sachs, according to emails from Biden's laptop. Biden abandoned his laptop at a repair shop in Delaware. The FBI now has the device.

The Pentagon contractor was Metabiota, a California-based pathogen research company.

The emails were sent during the Obama administration when Biden's father was vice president. They show the younger Biden introduced Metabiota to officials at Burisma, the Ukrainian gas company on whose board he served, for a project involving biolabs in Ukraine.

In 2014, the U.S. awarded $23.9 million to Metabiota, according to government records, and $307,091 of that total was allocated for "Ukrainian research projects."

The financial link between Hunter Biden and Metabiota's work in Ukraine was first reported by the National Pulse.

https://justthenews.com/government/security/biden-obama-and-ukraine-biolabs-separating-fact-fiction

Poisoning Fears: Ukraine warns peace team not to eat or drink during talks with Russians

 Following reports that Ukrainian peace negotiators and a Russian oligarch showed symptoms of having been poisoned after a meeting earlier this month with Russian officials, Kyiv has warned its negotiators to avoid meals and snacks during additional talks. 

"I advise anyone going for negotiations with Russia not to eat or drink anything, preferably avoid touching surfaces,” Ukrainian Foreign Minister Dmytro Kuleba said Tuesday while speaking to state media.

The warning is in response to suspicions that the negotiators were poisoned March 3, while meeting in Ukraine with Russian counterparts. According to reports that emerged this week, the victims experienced peeling skin on their faces and hands, along with painful tearing from their eyes.

The alleged victims included Russian oligarch Roman Abramovich, who has been acting as a back-channel conduit between Moscow and Kyiv.

Details of the incident were described on Monday in a series of tweets from Bellingcat, a Netherlands-based group that conducts and publishes open-source research. 

"Bellingcat can confirm that three members of the delegation attending the peace talks between Ukraine and Russia on the night of 3 to 4 March 2022 experienced symptoms consistent with poisoning with chemical weapons," the group wrote on Monday.

According to Bellingcat, the talks began March 3 in the afternoon, and lasted until about 10 p.m.

"Three members of the negotiating team retreated to an apartment in Kyiv later that night and felt initial symptoms – including eye and skin inflammation and piercing pain in the eyes – later that night," the organization wrote. "The symptoms did not abate until the morning."

The three men who felt the symptoms had consumed only chocolate and water, while a fourth person who ingested the same foodstuffs did not have symptoms.

Bellingcat tweeted that the symptoms were "most consistent with variants of porphyrin, organophosphates, or bicyclic substances."

Speculation quickly emerged that the men were poisoned by Russian hardliners who aimed to torpedo peace talks between Russia and Ukraine.

The theory is "shocking," but also improbable, one U.S. intelligence analyst told Just the News.

"It would be very tough to pull off, particularly in that setting," the analyst said. The analyst is not authorized to speak to the media, and made the comments on condition of anonymity.

Moscow denounced the suggestion that Russia had given poison to the negotiators. Such reports were false, and were part of an "information war," Kremlin spokesperson Dmitry Peskov said.

The Kremlin did not immediately return a request Tuesday for comment.

Another alleged victim, a member of the Ukrainian Parliament, on Monday downplayed the accounts.

"I’m fine," Rustem Umerov tweeted. "This is my response to all the yellow news spreading around. Please do not trust any unverified information."

The reports are part of a campaign to control the narrative surrounding events in Ukraine, he suggested.

"We have an informational war ongoing as well," Umerov also said in a tweet. 

More than three weeks after the alleged poisonings, the alleged victims, including Abramovich, have recovered and resumed their efforts to negotiate an end to the war in Ukraine.

https://justthenews.com/government/security/ukraine-warns-peace-team-not-eat-or-drink-during-talks-russians-fear-being

Amid growing criticism, CDC denies withholding vaccination data on COVID deaths, hospitalizations

 For the first time since COVID-19 lockdowns were imposed, the CDC finds itself under sustained scrutiny from even presumed allies for the quality and timeliness of data it publishes and what it keeps hidden.

The agency recently removed tens of thousands of deaths attributed to COVID through a "coding logic error," including a quarter of pediatric deaths. 

The CDC has only published "a tiny fraction" of its collected data, from booster performance in prime-age adults to "hospitalized patients stratified by age, sex, race and vaccination status," sources told The New York Times. 

One reason is fear the data could be misrepresented, including on vaccine effectiveness, agency spokesperson Kristen Nordlund told the newspaper. Scottish public health officials gave the same rationale when the country stopped reporting COVID deaths by vaccination status last month.

Newly released public records show the agency refusing to share its "demographic vaccine data at the state level" a year ago, instead directing a Harvard public health researcher to see if the CDC's "state and jurisdictional partners" post the data on their website.

Even as the agency works to unify federal and state public health data systems through its Data Modernization Initiative, some critics have accused the CDC of actively squelching statistics that undermine its preferred narratives. 

"The CDC is no longer releasing data comparing vaccinated vs unvaccinated deaths & hospitalizations," conservative writer Scott Morefield tweeted Saturday. "But don't worry. I'm sure it's just an oversight."

Nordlund told Just the News the agency is actually just working on a six-week lag with some data. Its most recent comparison of deaths used January data and wasn't released until mid-March, and the February deaths data will be released in mid-April, she said.

Its data tracker on cases and deaths, which covers 26 jurisdictions, has long emphasized that vaccinated and especially boosted individuals have better outcomes than the unvaccinated, though the data are more complicated. (Cases data run through mid-February.)

The January data show unvaccinated people ages 5 and up had a nine times greater risk of death than the fully vaccinated, and for ages 12 and up, 21 times greater than the boosted, though deaths fell sharply for all groups by the end of the month.

Cases across all groups also saw a steep plunge between early January and Feb. 19. The boosted even had a slightly higher positive rate per 100,000 than the vaccinated by the latter date. 

The fine print notes that deaths include anyone with a "positive specimen" and that a person isn't considered "fully vaccinated" or boosted until at least 14 days after receiving the primary series or booster. Those who only had one mRNA vaccine dose were excluded entirely.

The tracker's death data are "real time and subject to change" because they are often incomplete, Nordlund said regarding the CDC's recent removal of 72,000 COVID deaths. The National Vital Statistics System is the "most complete source of death data," given its death certificate review process. 

The CDC's "COVID-19-associated" hospitalization data by vaccination status are published more quickly, though they also cover just half the jurisdictions (13) as those reporting cases and deaths. The agency doesn't define "COVID-19-associated," and Nordlund didn't answer whether that includes COVID infections incidental to hospitalization.

Last week the agency posted hospitalization data through Feb. 26, showing that all children 5-11 and vaccinated 12-17 year-olds have a hospitalization rate under 1 in 100,000. Unvaccinated 12-17 year-olds (1.7) are comparable to boosted adults 18-49 (1.6). Unvaccinated 18-49 year-olds have a higher rate (8.7) than vaccinated 50-64 (5.7) but lower than even boosted individuals 65 and up (11.3).

None of the data includes relevant distinctions within each category, such as comorbidities and immune system condition. Unvaccinated groups are more likely to have medical conditions that make vaccination a higher risk for them.

The gap between unvaccinated and vaccinated has been closing since the Omicron variant emerged. The Epoch Times reported a month ago that vaccinated and boosted case rates jumped by 1,000 and 2,400 percent between Dec. 11 and Jan. 8.

Pfizer CEO Albert Bourla has admitted its vaccine offers "very limited protection if any" protection against Omicron infection, and even the booster is only "reasonable" against hospitalization and death.

Tweet URL

Those who have recovered from the first version of Omicron, known as BA.1, appear to have substantial immunity against its second, BA.2, according to Denmark's State Serum Institute.

Among 1.8 million infections Nov. 22-Feb. 11 with BA.1, only 47 people had reinfections with the even more transmissible BA.2 between 20 and 60 days later, "mostly in young unvaccinated individuals with mild disease not resulting in hospitalization or death," the government research group said.

While the Danish research is awaiting peer review, the U.K. Health Security Agency found a similar number of BA.2 reinfections (43) among more than half a million documented infections Nov. 1-Feb. 21.

The U.K. is also having a reckoning about the quality of its COVID data. The University of Oxford's Centre for Evidence Based Medicine recently reported the country has 14 definitions for COVID deaths and cited red flags, such as death certificates that implausibly claim COVID is the only cause and deaths attributed to COVID with no positive test.

In a Twitter argument about how to interpret U.K. data on COVID deaths by vaccination status, the University of Pennsylvania School of Medicine's Jeffrey Morris, director of its biostatistics division, said he doesn't trust the CDC's "data split by vaccination status" because "the lack of centralized system and great heterogeneity makes it more unreliable than most."

https://justthenews.com/government/federal-agencies/cdc-denies-withholding-data-vaccination-status-covid-deaths

Questions on feds' evidence for second COVID booster, refusal to consult advisers

 The federal government's enthusiasm for COVID-19 vaccine boosters is not matched by some of its outside advisers and other medical professionals, including the head of a leading medical journal who questions the evidence behind the decisions in the past several months.

The Food and Drug Administration on Tuesday authorized a fourth mRNA dose for ages 50 and older, expanding its availability beyond immunocompromised people, without input from its Vaccines and Related Biological Products Advisory Committee.

The Centers for Disease Control and Prevention followed hours later without consulting its Advisory Committee on Immunization Practices.

The FDA previously overruled VRBPAC in November by authorizing a third mRNA dose for ages 16 and older. The agency's top two vaccine officials, Marion Gruber and Philip Krause, resigned earlier in the fall when the Biden administration promoted boosters for all adults before the agency could weigh in.

Johns Hopkins University medical professor Marty Makary, a member of the National Academy of Medicine, asked sarcastically whether "bypassing the typical voting process" of the VRBPAC was "following the science."

Instead, the agency plans to convene its outside experts to "discuss" the FDA's decision, which is like "a judge issuing a verdict and then having lawyers make their arguments," Makary wrote in a tweet thread.

"There is zero clinical data that a 4th dose reduces hospitalization risk," he said. "There isn't even any evidence that a 3rd dose reduces hospitalization risk in young people."

VRBPAC member Eric Rubin, editor in chief of The New England Journal of Medicine, told CNN he has only seen fourth-dose data "for participants followed for just a few weeks." The committee needs to know how well it protects "highly vulnerable people against serious disease and death."

Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia and another VRBPAC member, said the committee has seen evidence only for "the possibility" that a fourth dose benefits those over 65. Without evidence for those over 50, "there shouldn't be this recommendation," he told CNN.

Former FDA Associate Commissioner Peter Pitts correctly predicted the FDA wouldn't "recommend" the second booster for ages 50 and up. The agency announcement Tuesday said the fourth dose "may be administered" to that age group, while the CDC said it was updating "recommendations to allow" the fourth dose.

Pitts told Just the News the FDA didn't have enough data to justify the "recommend" language. But "the data is crystal clear" that the second booster produces higher antibodies and thus "the benefit outweighs the risk" for that age group, which is why Pitts is fine with VRBPAC and ACIP being sidelined.

Authorizing a fourth dose would "cement a dangerous precedent: inadequate evidence being used to justify widespread vaccination for years to come," University of California San Francisco epidemiologist Vinay Prasad wrote last week in City Journal. "Pfizer and Moderna will get rich, our arms will ache, and no one will know if we made the right decision."

The agency is relying on "two observational studies comparing people who rushed to be boosted with those who didn’t," one of which showed an implausibly large benefit the day after boosting, while the other "relied on actively testing people with no symptoms," said Prasad, who once reported the FDA to Twitter for misinformation.

Former Harvard Medical School Dean Jeffrey Flier approvingly shared Prasad's longer review of one of those studies. "Until recently, nearly all scientists" would have demanded evidence from a randomized trial, Flier wrote. "Not clear how this changed."

Asked to respond to VRBPAC members' claims and criticisms from other doctors, FDA spokesperson Abby Capobianco told Just the News that the authorization "does not raise new scientific questions that would benefit from additional discussion" by VRBPAC.

She pointed to a press call with the FDA's Peter Marks, director of the Center for Biologics Evaluation and Research, who appeared in the agency video Prasad reported for misinformation.

Marks told reporters "this was a relatively straightforward decision made based on data ... such as the survival benefit [and] the reduction of hospitalization." While he admitted the agency only had data on ages 60 and up, Marks said the FDA set the floor at 50 because "a significant enough group of people in that range that would be at high risk, and this reduces confusion for people with a very good [second booster] safety profile."

The CDC didn't answer whether the FDA's action prompted it to authorize the second booster as well, or respond directly to criticism from outside doctors.

Spokesperson Kate Grusich told Just the News the CDC "values" ACIP and the "voluntary service of its members," but to "ensure the best use of resources both internally and externally, some incremental changes to vaccine policy do not need to go before the full committee."

Its vaccine experts and ACIP's Vaccines Work Group "reviewed the available data and the CDC Director approved these updates" for the benefit of "those at highest risk for severe outcomes," Grusich said, but did not answer what feedback the ACIP work group provided and how Walensky responded to it.

Prasad also warned that vaccine mandates in "ultra-low-risk populations" were certain to stiffen when the feds authorize fourth doses for younger populations. Many colleges already require third mRNA shots for students, and the University of California's booster policy also applies to a school it runs with students as young as 12, he said.

A new study by University of Washington pediatrics researchers casts doubt on claims that the post-mRNA vaccination heart inflammation observed at higher rates in young people is mild or short-lived.

Accepted for publication in the Journal of Pediatrics, the Seattle Children's Hospital study tracked 35 patients diagnosed with myopericarditis within a week of receiving a second Pfizer dose. The final cohort was composed of 16 patients who had "acute phase and follow-up CMR [cardiac magnetic resonance studies] available for review."

All but one were male, and all but two were non-Hispanic white, with a median age of 15.

They all had chest pain, and 10 of the 16 had an "abnormal electrocardiogram." The median time between vaccination and treatment with nonsteroidal anti-inflammatory drugs was 2.5 days.

At their followup CMR 3-8 months later, 11 of the 16 had "persistent" late gadolinium enhancement (LGE), or scarring, "although there was a significant decrease in the quantifiable" percentage of LGE.

Philadelphia cardiologist Anish Koka said this scarring had not been observed in studies of multi-system inflammatory syndrome in children (MIS-C) myocarditis, which results from COVID infection.

"Vaxx myocarditis is worse than MIS-C myocarditis," he tweeted.

University of Pittsburgh medical professor Walid Gellad, director of its Center for Pharmaceutical Policy & Prescribing, responded that he wouldn't call it "worse." But the research undermines the claim that children "fully recover" from vaccine-associated heart inflammation – talking points that some doctors "casually parroted."

The CDC "has a civic duty to ... rigorously study the long-term effects of vaccine-induced myocarditis" given this study, Makary of Johns Hopkins tweeted. A week earlier, other medical experts pointed to a small Israeli study of boosted adults, ages 18-44, that also found LGE in patients referred for CMR within 21 days of the booster.

https://justthenews.com/government/federal-agencies/medical-experts-question-fdas-evidence-second-covid-booster-refusal

AHA redirects FTC, DOJ merger scrutiny from hospital deals to concentrated insurer markets

 As federal regulators work to overhaul merger and acquisition enforcement, hospitals say the industry’s guidelines “do not need major revisions” outside of two new measures related to the potential benefits of hospital consolidation.

In a March 30 letter to the Department of Justice (DOJ) and the Federal Trade Commission (FTC), the American Hospital Association (AHA) reinforced its merger-friendly position by referring the agencies to recent data on the positive outcomes of provider consolidation.

These reports and studies—some of which were conducted on behalf of the trade group—suggest efficiencies enabled by mergers allow hospitals to reduce costs, improve quality, better coordinate services or improve access by helping struggling facilities keep their doors open.

“For these reasons, it is essential that the antitrust agencies employ analytically sound merger guidelines that fairly account for the lifesaving benefits that hospital mergers produce,” AHA General Counsel Melinda R. Hatton wrote in the letter. “Changes to the guidelines should reflect years of scholarship that have documented these pro-competitive efficiencies.”

The FTC and the DOJ began soliciting public input on merger enforcement in January in the wake of “an ongoing merger surge that has more than doubled merger filings from 2020 to 2021.” The agencies received their directive last summer from President Joe Biden, who specifically called out hospital dealmaking as a driver of higher prices and consumer harm.

The AHA wrote in its letter that hospitals and other parties “rely on the merger guidelines for predictability and transparency of what constitutes lawful conduct” and that recalibration should only be considered for “significant developments in antitrust law and economics.”

Rather, AHA sought to redirect the regulators’ focus by advising the DOJ and the FTC to use the recently passed Competitive Health Insurance Reform Act (CHIRA) to “investigate and challenge anticompetitive mergers and deceptive conduct by insurance companies.”

Insurers, the provider group wrote, already operate highly concentrated markets permitting them to raise prices, restrict competition and limit patient choices. The AHA also referenced insurers’ “bait-and-switch tactics” to unexpectedly change coverage and restrictions on specialty drugs as harmful results of an under scrutinized slice of the healthcare industry.

“The current guidelines allow the agencies to challenge deals like UnitedHealth Group's proposed acquisition of Change Healthcare, a suit that was recently and rightfully brought by the DOJ,” the AHA wrote. “The AHA strongly urges the agencies to investigate and pursue these anticompetitive practices by health insurers using the powers granted to them by the passage of CHIRA.”

Still, the AHA’s letter did outline two hospital-specific guideline revisions for the agencies to consider.

The group first suggested that agencies “correct defects in the economic models they use to evaluate hospital transactions.”

For instance, a demand model FTC uses to predict how many patients view merging hospitals as their top two choices “overemphasize how much value patients assign to travel times and ignore other important considerations that affect how consumers select a hospital, such as past treatment experiences, where patients' physicians have admitting privileges and physician referrals,” AHA wrote.

The trade group also asked regulators to update their guidelines to recognize care coordination improvements enabled by hospital mergers.

“Economic research has shown that partnering with hospital systems typically enables the acquired hospital to provide measurable benefits to patients in the form of lower health care costs, improved patient care and better access to providers,” the AHA wrote. “The agencies and the guidelines should recognize these additional benefits to hospital mergers.”

The AHA’s support for hospital consolidation grapples with numerous studies published over the last several years suggesting that healthcare providers’ increased market power drives higher charges, service line cuts and fewer incentives to improve care.

https://www.fiercehealthcare.com/providers/aha-redirects-ftc-doj-merger-scrutiny-away-hospital-deals-concentrated-insurer-markets