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Wednesday, November 10, 2021

Biogen, Eisai Update On Phase 2b, 5-Year Lecanemab Data At Clinical Trials On Alzheimer's Disease

  Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Michel Vounatsos, "Biogen") announced today results of new clinical, biomarker and safety assessments of brain amyloid reduction and five-year clinical status of people living with early Alzheimer's disease (AD) from the lecanemab Phase 2b 201 and the open-label extension (OLE) studies. The findings were presented and discussed in a late-breaking roundtable session with esteemed clinical researchers at the 2021 Clinical Trials on Alzheimer's Disease (CTAD) conference, November 9-12, 2021, in Boston, Massachusetts and virtually. Eisai recently initiated a rolling submission of a Biologics License Application (BLA) for lecanemab, an investigational anti-amyloid beta (Aβ) protofibril antibody, for the treatment of early AD, to the U.S. Food and Drug Administration (FDA) under the accelerated approval pathway.

OLE Study Explores Biomarkers and Clinical Effects Across Five Years

An OLE with 10 mg/kg IV biweekly lecanemab dosing was implemented after analysis of the 18-month, core phase (Study 201, Alz Res Therapy 13;21) with an intervening off-treatment period (gap period) ranging from 9-59 months (mean 24 months). The OLE phase evaluated the effect of lecanemab on amyloid PET over 12 months of treatment, including earlier time points (3 and 6 months) than in the core phase (12 and 18 months). This study design provided the opportunity to explore the biomarker and clinical effects of stopping and restarting lecanemab across five years of disease trajectory.

Amyloid Reduction Correlates with Clinical Benefit
The updated assessment of the OLE phase showed that treatment with lecanemab resulted in reduction of brain amyloid levels in as early as 3 months based on OLE data and robust clearance of amyloid plaque with more than 80% of participants (10/12) achieving amyloid negative status by 12-18 months of treatment as measured by PET (visual read). These results are consistent with core phase results. The 201 study core data suggested that clinical efficacy (ADCOMS) is correlated with amyloid reduction (PET SUVr) at both the population (correlation coefficients=0.832, p-value=0.080) and subject levels (correlation coefficients=0.201, slope=0.199, p=0.036). Amyloid PET levels were significantly reduced by quantitative assessment in newly treated OLE subjects in as early as 3 months after initiation of treatment. Additionally, the core data suggested that clinical efficacy is correlated with plasma Aβ at both the population (correlation coefficients=-0.306, not significant) and subject levels (correlation coefficients=-0.208, slope=-3.957, p-value=0.050).

The presentation video and slides will be available on the investors' section of the Eisai Co., Ltd. Website by 10:00 p.m. U.S. EST on November 11.

UNITY Biotechnology update post-Q3 report

 UBX1325 Phase 2 study in DME currently enrolling, with additional Phase 2 study in AMD planned for 1H22

UNITY to present at invitation-only Eyecelerator innovation conference at AAO

UNITY Biotechnology, Inc. (UNITY) [NASDAQ:UBX], a biotechnology company developing therapeutics to slow, halt, or reverse diseases of aging, today reported financial results for the third quarter ended September 30, 2021.

“In our Phase 1 clinical study, UBX1325, a senolytic small molecule working through an entirely new mechanism of action, has shown a favorable safety profile and very promising evidence of biological activity through six months, demonstrating durability,” said Anirvan Ghosh, Ph.D., chief executive officer of UNITY. “As announced yesterday, we share the excitement of the patient and physician community about the potential for UBX1325 as a possible disease-modifying treatment to fill the large and unmet need for options beyond anti-VEGF therapies. Our team continues to advance the UBX1325 program in a Phase 2 proof of concept study currently enrolling patients with diabetic macular edema (DME), and we are using the promising data from patients with age-related macular degeneration (AMD) in the Phase 1 study to inform design of a Phase 2 study in wet AMD to start in the first half of 2022.”

UNITY yesterday released 24-week data from its Phase 1 study of UBX1325 in DME, along with 24-week and 12-week (AMD-only cohort) data in patients with AMD, and will present information about the UBX1325 program at Eyecelerator@AAO 2021 in New Orleans on November 11, 2021, an invitation-only event featuring ophthalmic innovation put on in partnership between the American Academy of Ophthalmology and ASCRS.

Upcoming Milestones

  • UBX1325 Phase 2a proof of concept study in DME had a first patient dosed in June 2021 and is actively recruiting patients, with information about that trial available here. Twelve-week safety and efficacy data are expected in the first half of 2022.

  • UBX1325 Phase 2 proof of concept study in AMD is expected to initiate in the first half of 2022, with twelve-week safety and efficacy data expected in the second half of 2022.

  • UBX2050 (Tie2 mAb) and UBX2089 (alpha-Klotho) expected to enter IND-enabling studies in 2022.

U.S. Judge Halts Johnson & Johnson Talc Litigation for 60 Days

 A U.S. bankruptcy judge on Wednesday put a 60-day halt on tens of thousands of legal claims against Johnson & Johnson that allege its talc-based products cause cancer.

U.S. Bankruptcy Judge Craig Whitley ordered the halt at a hearing in Charlotte, North Carolina.

He also decided to transfer the talc cases to a federal court in New Jersey, where J&J is based and where much of the nationwide litigation over its talc products is being conducted.

Whitley ruled in response to a request from LTL Management LLC, a J&J unit created by the parent company to hold its talc liabilities, to halt the talc cases while it pursued a Chapter 11 restructuring. The parent did not file for bankruptcy.

Shares of J&J were up about 1% after the ruling.

The New Brunswick, New Jersey-based company has maintained that its talc products are safe.

https://money.usnews.com/investing/news/articles/2021-11-10/us-judge-halts-johnson-johnson-talc-litigation-for-60-days

Drug pricing bill’s unintended consequences will distort drug development

After months of wrangling, Democratic lawmakers have agreed on a drug pricing bill. The House could vote on it within days.

If it becomes law, we’re going to see some unfortunate consequences that legislators can’t possibly have intended. By ignoring what they may have thought were minor details, they’re about to distort the entire drug-development ecosystem to society’s detriment.

In an attempt to save the government money, the proposal allows Medicare to impose price controls on a range of prescription medicines after varying lengths of time on the market. Those price controls, and the complex rules and caveats surrounding them, will deter investors like me from backing certain research projects, skewing the kinds of drugs patients will eventually have access to.

Let’s look at some of the adverse consequences.

First, the drug pricing bill would ironically encourage drug companies to concentrate on complex, large molecule “biologic” drugs — which are typically injected — instead of small-molecule drugs typically taken in pill form that are easier and cheaper to make and administer. That’s because the legislation would make small-molecule drugs eligible for price controls nine years after they launch, whereas biologics would be shielded from price controls for 13 years.

If lawmakers must skew the playing field one way or the other, they should encourage the development of drugs that are easier for patients to take and that tend to go generic more quickly and efficiently. Instead, Congress is poised to incentivize companies to develop biologics that are, on average, more expensive to produce and more difficult for patients to take — and to take as prescribed — often requiring physicians to administer them, adding to costs.

In so doing, the proposed drug pricing bill would also undermine a part of President Biden’s agenda: curing cancer. Numerous cancers have intracellular targets — proteins inside cancer cells — that can be “drugged” only with small molecules that are able to get into cells, not large biologic molecules that can’t. Championing a cancer moonshot while discouraging research into small molecules is like saying you want to go to the moon while discouraging the use of rockets.

Second, the price-control scheme would discourage companies from seeking new uses for existing drugs.

These days, companies continue to discover new diseases they can treat even a decade after a drug has launched, because they still have time to turn a profit. For example, after the Food and Drug Administration approved the first SGLT2 inhibitor to treat diabetes in 2013, companies saw signals by 2016 that these drugs might also treat heart failure. After running a big, expensive, risky trial, AstraZeneca sought FDA approval for Farxiga (dapagliflozin) to treat heart failure — and received that approval in 2020, after which the company still had 10 years of market exclusivity during which to profit from that investment without generic competition.

If exclusivity had been limited to nine years, the price of AstraZeneca’s drug would be scheduled for mandatory control in 2023. That means that back in 2016, when the AstraZeneca would be considering whether to invest in the heart failure trial, it would see that it would have less than three years between an approval in 2020 and price controls in 2023 during which to generate a return from its investment, and might very well have decided not to make that investment. Considering that SGLT2 inhibitors save lives and avert expensive hospitalizations, society would have borne that loss.

The reward for developing effective small-molecule drugs should be kept appropriately long, around 13 to 14 years.

Third, the drug pricing bill does away with an important incentive to run pediatric clinical trials, which are essential to learn about the effectiveness and appropriate dosage of new medicines for children.

Existing law gives drug companies a six-month pediatric extension on their exclusivity period to encourage trials in kids. The new law would send drug development back to an era when scientists, doctors, and parents struggled to get data on how to treat children with adult drugs.

I hope lawmakers are still thinking through the potential consequences of their proposal — and remain open to revisions before it goes to the floor. The ultimate victims of all the unintended consequences of the current proposal will be all of us as future patients.

Peter Kolchinsky is a founder and managing partner at RA Capital Management and author of “The Great American Drug Deal” (Evelexa Press, 2020).

https://www.statnews.com/2021/11/09/unintended-consequences-drug-pricing-bill-distort-drug-development/

Data broker shared location data with DC government for coronavirus tracking

 A data broker shared billions of phone location records with the Washington, D.C., government for coronavirus tracking last year, according to public records obtained by the digital rights group the Electronic Frontier Foundation (EFF).

The broker company, Veraset, shared the data with D.C. officials as part of a free trial that was ultimately not turned into a full contract. The data was authorized only for coronavirus tracking and did not include names or other personal details about individuals, according to EFF.

There was no evidence of misuse, though EFF argued that the case shows potential for abuse of information collected and sold by data brokers.

“Veraset’s data is harvested from users without meaningful consent, and is monetized by giving corporations and businesses detailed information about the day-to-day movements of millions of people,” EFF staff technologist Bennett Cyphers wrote in a blog post.

“At a minimum, DC should have performed more vetting of Veraset’s sources, implemented stronger privacy protections, and justified the acquisition of such sensitive data.”

The D.C. Office of the Chief Technology Officer (OCTO) and The Lab @ DC, a division of the Office of the City Administrator, both uploaded the data from Veraset to the District’s unified data storage and sharing system.

According to emails obtained by EFF, local officials “didn’t find a use case” for the information.

Data brokers — which collect information from a wide variety of sources, package it and sell it to government and private companies alike — have come under scrutiny in recent years.

The purchase of data on individuals by government agencies, including the Department of Homeland Security and Defense Intelligence Agency, without a warrant has garnered particular attention from lawmakers.

Sen. Ron Wyden (D-Ore.), who introduced legislation earlier this year requiring warrants for such purchases, said that data brokers are trying to exploit the pandemic to launder their reputations.

“It’s no surprise that shady data brokers want to exploit the pandemic to put a positive spin on their sale of Americans’ private information to the government,” the Oregon lawmaker said in a statement to The Hill. “The unregulated trade in detailed location data creates serious safety risks for American families.”

The Hill has reached out to the Washington government for comment. 

https://thehill.com/policy/technology/580975-data-broker-shared-location-data-with-dc-government-for-coronavirus

Colorado implements crisis standards of care plan amid staffing shortages

 Colorado activated its crisis standards of care plan on Tuesday to help hospitals determine how to allocate limited staff as emergency shortages and COVID-19 admissions rock health systems across the state.

The state implemented the crisis standards specifically to allow hospitals to prioritize certain health workers for care, as almost 40 percent of hospitals expect shortages within the next week, according to state data

Under the crisis standards of care, Colorado aims to increase the availability of health care workers, while improving workplace safety and worker resilience in the midst of the ongoing pandemic.

Activating staffing crisis standards of care allows health care systems to maximize the care they can provide in their communities with the staff they have available,” state chief medical officer Eric France said.

But the activation of crisis standards of care does not mean residents should avoid “necessary health care,” he said, including going to the emergency room.


Twenty months into the pandemic, Colorado health care workers, like many across the country, are facing COVID-19 infections, higher work volumes and burnout, which all contribute to the staffing shortages. 

To address this, the state suggests decreasing meetings and administrative responsibilities during such a crisis, cutting down on documentation requirements and changing staff schedules to prevent fatigue. 

Hospitals need to inform the Colorado Department of Public Health & Environment when activating and deactivating the crisis standards of care.

The state’s crisis of standards of care are not in effect for emergency medical services, hospitals and acute care facilities, out of hospital care providers or personal protective equipment. Elective procedures are still permitted, although the department noted individual hospitals can decide to halt them to redistribute staff. 

For patients, the crisis standards of care for staffing may alter the ratio of staff to patients, allowing health care workers to “attend to more patients,” according to the department.

Gov. Jared Polis (D) has already sought to block any hospital overflow through an executive order that allows health systems to transfer patients so hospitals can stay under capacity. 

The state currently has 72 percent of its hospital beds full, including 12.6 percent with confirmed COVID-19 patients, according to data from the Department of Health and Human Services. 

In intensive care units, 85 percent of beds are occupied, including 35 percent with confirmed coronavirus patients. A total of 51 percent of its critical care ventilators are occupied, according to state data.

More than 80 percent of Colorado adults have received at least one shot.

https://thehill.com/policy/healthcare/580925-colorado-implements-crisis-standards-of-care-plan-amid-staffing-shortages

Will Supreme Court accept Biden's vaccine 'work-around' as constitutional?

 The Biden administration was hit by a broadside last week, when the U.S. Court of Appeals enjoined its use of the Occupational Safety and Health Administration (OSHA) to implement a national vaccine mandate as a matter of “workplace safety.” Not to be deterred, the administration reportedly is pushing forward with a possible extension of that rule to small businesses. 

White House chief of staff Ron Klain professed “confidence” that they have found what he previously admitted was a “work-around” of the Constitution, which does not give the president such authority. After all, Klain argued this week, this is no different than requiring hard hats in the workplace.

Klain’s confidence may run into serious constitutional doubts in the courts, however. Indeed, he and other White House officials may be making the case for the 24 states challenging the mandate.

Supreme Court Justice Oliver Wendell Holmes once wrote that “hard cases make bad law.” The same thing might be said about hard-hat arguments. Klain has suffered from an abundance of confidence when some prudence may be preferred at the Justice Department. Like President Biden, he has vacillated between claiming the authority to require vaccinations and then backtracking to claim only the authority to “urge” vaccinations.

Biden eventually acknowledged that he does not have the authority to order a national mandate directly. That is when Klain again confidently rushed in where wiser government lawyers fear to tread. He announced that the White House had found a way to evade the constitutional limitations: “OSHA doing this vaxx mandate as an emergency workplace safety rule is the ultimate work-around for the Federal govt to require vaccinations.”

Many of us often criticized former President Trump for undermining Justice Department lawyers with damaging comments later cited by courts when ruling against his administration. Now Biden and Klain seem to be competing for the greatest admissions-against-interest, including a prior admission from President Biden that they would be pursuing a presumptively unconstitutional measure simply to buy more time to spend more money. Klain is celebrating a way to evade constitutional limitations — but for courts reviewing the OSHA rule, that is akin to a husband telling a spouse that he has found a “work-around” to his vows by redefining extramarital relations.

On Sunday, Klain further explained that the OSHA rule is “common sense . . . if OSHA can tell people to wear a hard hat on the job, to be careful around chemicals, it can put in place these simple measures to keep our workers safe.”

The problem is that OSHA itself failed to see that “common sense” meaning until the White House pushed the work-around. After President Biden announced that OSHA would make the declaration, the agency appears to have reverse-engineered its interpretation to fit the order. For years, OSHA debated whether it can or should issue an "Infectious Diseases Regulatory Framework" covering "airborne infectious diseases." It has never issued such a framework and, in the past, has done no more than requiring employers to offer workers such things as Hepatitis B vaccination.

Moreover, OSHA is using a work-around of its own to avoid the rule-making process, which can take a great deal of time and require the agency to answer a great many questions. OSHA used an "emergency temporary standard" (ETS), but that applies to a "grave danger" when such action is "necessary to protect employees from such danger." The ETS, however, is designed to protect employees "from exposure to substances or agents determined to be toxic or physically harmful, or from new hazards." It can only be used in emergencies when "necessary to protect employees from such danger." It is not a rule to be used for convenience so a president can impose a mandate indirectly that he cannot impose directly.

OSHA regulations are designed for dangers inherent in a given workplace or industry. In the case of hard hats, things fall, and workers need to protect their heads. Likewise, if workers are being exposed to a toxic chemical in a given industry, that industry can face an ETS. The idea is to stop businesses from creating dangerous conditions once people enter workplaces.

But this national vaccine mandate is different. The administration arguably is using the workplace to make society at large safer. White House deputy press secretary Karine Jean-Pierre seemed to make that point on Monday when she insisted that OSHA clearly has this authority because “more than 750,000 people have died of COVID. You have approximately 1,300 people a day, who continue to die a day, as I said, from COVID. If that's not a grave danger, I don't know what else is."

However, those are people dying in society at large, not in workplaces. While some may have contracted the virus in the workplace, courts may demand a closer nexus to a “grave danger” inherent in the workplace. The White House has expressly admitted that it is seeking to “reduce the number of unvaccinated Americans by using regulatory powers and ... these requirements will become dominant in the workplace.” 

It is not even clear that the rule is necessary. Courts have uniformly upheld the right of employers to impose mandatory vaccination or testing requirements as a condition for employment; states have enhanced authority over such public health measures, too.

This is, admittedly, a novel issue, and there are good arguments on both sides. But it also is a generally-worded statute that can be interpreted broadly, and I expect a split in court decisions — and that only increases the likelihood of a Supreme Court review. Once there, the Biden administration could be giving some justices an opportunity to review not mandates but OSHA’s discretion over such mandate orders. A majority of the court has shown an interest in rolling back the so-called Chevron Doctrine, which affords agencies great deference in the interpretation and enforcement of federal law.

After long debating whether it even has this authority, OSHA has suddenly found it, and then has issued one of the most comprehensive health-based standards in its history — all without rule-making or debate. Ironically, the Supreme Court warned against such sudden agency “finds” of regulatory authority. In 2014, the court ruled that “When an agency claims to discover in a long-extant statute an unheralded power to regulate a significant portion of the American economy, we typically greet its announcement with a measure of skepticism. We expect Congress to speak clearly if it wishes to assign to an agency decision of vast 'economic and political significance.’”

Indeed, the Court recently rejected Biden’s effort to continue the eviction moratorium under the same type of sweeping interpretation by saying “[i]t strains credulity to believe that this statute grants the [agency] the sweeping authority that it asserts.”

In other words, Klain’s confidence may not be shared by some on the court.

The Justice Department will have to find a way around Klain’s “work-around” rationale. It also will need more than a hard-hat rationale in this “hard case,” if it wants to avoid bad law.

Jonathan Turley is the Shapiro Professor of Public Interest Law at George Washington University. 

https://thehill.com/opinion/judiciary/580880-will-supreme-court-accept-bidens-vaccine-work-around-as-constitutional