CMS' Biogen decision could spell problems for Lilly, Roche Alzheimer's drugs, half of surveyed neurologists say

 Neurologists in the U.S. are agreeing with a new draft decision from the Centers for Medicare & Medicaid Services (CMS) that restricts reimbursement of Biogen’s controversial Alzheimer’s disease drug, Aduhelm, to Medicare patients enrolled in approved clinical trials only. In fact, half of those surveyed said CMS' decision would hit how they prescribe the rival drugs waiting in the wings that are also included in CMS' decision.

The CMS verdict was handed down Jan. 11, and, that week, Spherix sent out a survey to 75 neurologists and conducted follow-up calls to feel out the mood.

The decision, which is yet to be finalized, “could effectively spell the end for Aduhelm,” RBC Capital Markets analyst Brian Abrahams said in a note to clients mid-January.

That’s because older people covered by Medicare make up the bulk of the Alzheimer’s patient population, and restrictive access for them would be a serious blow to Aduhelm’s market potential, which had been pegged by analysts at Evaluate as reaching $4.9 billion at peak.

CMS' draft decision also applies to other anti-amyloid monoclonal antibodies (mAbs) still in development, including Eli Lilly’s donanemab, Roche’s gantenerumab and Biogen’s follow-up mAb, lecanemab, which is in development with Eisai.

Lilly is the most well known drug on the horizon, according to Spherix's report based on its survey. “Among the three late-phase emerging anti-amyloid mAbs in development for Alzheimer’s disease, unaided awareness is highest with Lilly’s donanemab,” the report notes.

Yet, around half of those surveyed said that should the CMS’ decision stick and be held for other mAbs, this would negatively impact their prescribing behavior. “One in two neurologists [48%] anticipate that CMS’ proposed NCD decision being finalized as such would have a negative impact on their willingness to prescribe donanemab as well as the other anti-amyloid mAbs lecanemab and gantenerumab.”

The CMS decision is expected to get finalized by April and could yet be changed, but that could be a big hit for these drugs, with donanemab and gantenerumab expected to hit 2026 sales of $6 billion and $2.5 billion, respectively, according to estimates by Evaluate made prior to the CMS decision.

There was overall a “lack of consensus” from neurologists when it came to these drugs given how similar they are to Aduhelm, though most are waiting for more data to make a decision as to whether they should be used and reimbursed.

One neurologist said to Spherix: “If Lilly had very strong data on clinical benefit [with donanemab], not just clearing of amyloid, and on the side-effect profile, I hope that CMS would change its decision for that particular drug.”

Biogen is working on a confirmatory trial for Aduhelm, a mandate of its FDA accelerated approval, though results are not expected soon. In December 2021, Biogen said it anticipates starting to screen patients this May and that the trial would likely take around four years to complete. Lilly, meanwhile, expects to have a first readout from its ongoing trial by 2023 and is also running a head-to-head against Aduhelm, with a readout slated for year-end.

“Given neurologists’ mixed opinions, it is perhaps not surprising that they believe that positive phase 3 data on cognitive and functional outcomes with acceptable safety from ongoing trials with late-phase agents would likely motivate CMS to loosen coverage in a revised reimbursement decision,” the report said.

Overall, the neurologists agreed with the CMS that Aduhelm should be restricted, with 55% agreeing and 33% neutral (while 15% disagreed), and generally saw the CMS in a positive light. The same could not be said for the FDA, however.

The agency approved Aduhelm nearly one year ago with what was, initially, a very broad label despite there being serious questions over efficacy and safety. In fact, in November 2020, the drug was rejected by the FDA’s expert advisory panel.   

Since then, the FDA narrowed Aduhelm's label, and Biogen ended up slashing the drug's price in half from $56,000 at launch. But the damage was already done. “Neurologists’ confidence in the agency has been eroded in the past year,” the report found.

Conversely, their confidence in CMS has remained on par (or has improved) over the past year.

A neurologist interviewed by the firm, who was not named, said: “The FDA is very concerning. The [AdComm] recommended against [Aduhelm's approval], and then the FDA went around and said yes, so you lose a lot of confidence right now.

“My confidence in CMS is much better, much improved. I think they did the right thing. I think this is necessary. Too expensive and too potentially harmful to just willy-nilly start using these medications. We need to know definitively that these are really beneficial.”

 The CMS will take comments on its decision through Feb. 10.

https://www.fiercepharma.com/marketing/half-neurologists-unlikely-to-prescribe-lilly-roche-alzheimer-s-drugs-if-cms-biogen

Novartis' Sandoz reportedly the target of $25B buyout bid from Carlyle and Blackstone

 As Novartis reviews its generics business, the list of potential Sandoz suitors has grown. The deal could become one of the biggest generic industry acquisitions ever—assuming an offer makes it across the finish line.

Investor groups Blackstone and Carlyle could join forces on a massive $25 billion bid for Sandoz, Bloomberg reports, citing people close to the matter. The private equity firms are discussing a potential joint offer for the Novartis unit, the publication said. Separately, Advent International, Hellman & Friedman and KKR & Co. are sizing up their own approaches, Bloomberg’s anonymous sources said.

Sandoz is a sizable target, so it could make sense for investor groups to merge their bids. But it’s early yet, and the suitors may decide against teaming up or proceeding with bids altogether, Bloomberg said.

The interest in Sandoz comes as Novartis takes a magnifying lens to the business. In October, the Swiss drugmaker launched a strategic review of its generics arm, leaving all options on the table. Novartis said it would provide an update by the end of 2022.

It’s not unusual for private equity firms to unite on the hunt for big acquisitions, Bloomberg notes. Blackstone, Carlyle and Hellman & Friedman in June agreed to buy medical supply company Medline Industries for a whopping $30 billion, for example. Hellman & Friedman also partnered with Bain Capital in November to snap up medical IT outfit Athenahealth for $17 billion.

Meanwhile, Sandoz has already attracted some interest. In November, German newspaper Handelsblatt reported that Swedish-based investment group EQT and Germany’s Struengmann family were weighing a joint move to buy the Novartis unit for $21.6 billion. Interestingly, Struengmann twins Thomas and Andreas are no strangers to Novartis, having sold it their generics maker Hexal back in 2005. They’re also primary investors in Pfizer’s COVID-19 vaccine partner BioNTech.

That same month, Novartis CEO Vas Narasimhan confirmed interest in the company: “There have been various requests for more information, but no concrete offers,” he told German magazine WirtschaftsWoche. 

Whether it’s $21 billion or $26 billion, a successful Sandoz buyout could eclipse every other M&A deal from last year. 2021 saw a relative lull in merger and acquisitions activity by drugmakers—though 2022 seems poised for a rebound.

https://www.fiercepharma.com/pharma/novartis-sandoz-reportedly-target-26b-buyout-bid-from-carlyle-and-blackstone

Novartis forecasts 2022 sales and profit growth; Sandoz review continues

 Novartis forecast its sales and core operating profit would grow at a mid-single-digit rate this year, as the Swiss pharmaceuticals group nears a decision on whether to keep or sell its generics business Sandoz.

The pharmaceuticals company in October raised the prospect of divesting Sandoz after years of revamping the business, as price pressures mount in the off-patent drug sector.

In its earnings statement on Wednesday, Novartis reiterated that it would provide an update by the end of 2022 as it explores a possible sale but also an option to retain the off-patent drugs unit.

Media reports have cited interest from private equity firms, in particular and Chief Executive Vas Narasimhan has said the asset was attracting interest from various suitors.

In a media call on Wednesday, the CEO said all options were still on the table.

"We don’t have a bias towards any of these options at the moment. We are doing the work to finish the carve-out financials to provide that to relevant parties and we’ll see what proposals come back," the CEO said.

Core operating income for the fourth-quarter ended Dec. 31 gained 9% to $3.8 billion, as higher drug sales offset in increase in marketing and development costs.

Revenues from arthritis and psoriasis drug Cosentyx gained 13% to $1.24 billion, slightly below average analyst expectations of $1.3 billion, based on Refinitiv data.

Novartis' revenues from heart failure treatment Entresto jumped 34% to $949 million, broadly in line with the market consensus.

It forecast Sandoz sales would be broadly in line with the 2021 level of $2.5 billion, while the division's core operating income was expected to fall at a low-to-mid-single-digit rate.

Despite plans to buy back up to $15 billion worth of shares until the end of next year, Novartis has said it would retain enough spending power to buy companies and technologies, back its own research efforts and pay attractive dividends.

It proposed raising its dividend 3.3% to 3.10 Swiss francs ($3.37) per share, the 25th consecutive increase since its creation.

https://www.marketscreener.com/quote/stock/NOVARTIS-AG-9364983/news/Novartis-forecasts-2022-sales-and-profit-growth-Sandoz-review-continues-37717327/

U.S. is failing to care for traumatic brain injury survivors

 Every year, nearly 5 million Americans are evaluated for traumatic brain injury in emergency departments across the country.

These injuries can happen in many different ways -- from car crashes and military conflict to falls and everyday activities -- and they're diagnosed in around 2% of all United States emergency department visits.

Awareness of the magnitude of TBIs has increased over the last several decades, particularly in sports and the military. But a group of experts from across the nation say the country's current system of care is often failing to meet the needs of the individuals, families and communities affected by traumatic brain injury.

"We as physicians are frustrated that there are significant limitations to what we can do for our patients for an injury that has real-life, debilitating consequences," said Frederick Korley, M.D., Ph.D., associate professor of emergency medicine at Michigan Medicine. "There are many important, structural changes that need to be made to provide better care for patients who often go through a prolonged recovery process."

Korley is part of a select team of researchers who recently authored a report analyzing the health care system's response to TBI for the National Academies of Sciences, Engineering, and Medicine. The study, funded by the U.S. Department of Defense, found that the lack of a comprehensive framework for classification, care and research poses significant burdens for everyone involved -- leading to needless death, squandered human potential and soaring costs. Their report contains numerous recommendations for improving TBI care and research.

TBI classification

When those near-5 million Americans arrive at the ER each year to be evaluated for brain injuries, they are placed into one of three categories: mild, moderate or severe.

It seems simple. The driver who is comatose after a devastating car crash would be considered severe, while the student who has a headache after slipping on black ice could be seen as mild. To Korley, who sees many of these so-called "mild" cases in the emergency department, the classification is inadequate -- and, in some cases, insulting to patients.

"Some people who are considered 'mild' can't go to work; they have horrible headaches and memory problems that can result in losing a job or dropping out of school," he said. "Conversely, there are some people classified as 'severe' but actually do way better than we expect. Those cases don't all result in death or devastating disability."

This lack of distinction, the report notes, leads to suboptimal care across the spectrum of TBI and can include withdrawing life-sustaining treatment for patients who could have improved.

Instead of the shorthand, the researchers recommend using the full Glasgow Coma Scale score, a system that grades the severity of TBI on a scale from three to 15, in addition to results from brain CT scans and blood tests to classify patients. This approach provides a more accurate, nuanced assessment of the injury, Korley said.

"Let's say we have two cases of 'mild' TBI," he said. "One is a patient who has a concussion and experienced light sensitivity but felt fine not long after, and the other is someone who is awake but so out of it that they ask the same question repeatedly. The first would be a GCS 15, and the second would be a GCS 13. Calling both patients 'mild' is an oversimplification. Saying one is a GCS 15 TBI and the other is a GCS 13 TBI is more descriptive and will inform additional treatment plans."

Emergency physicians also rely heavily on neuroimaging through CT scans to find evidence of brain bleeding and determine if surgery is necessary. Recently, they have started using blood tests to justify neuroimaging and reduce the number of unnecessary scans. These blood tests can also help physicians better characterize the severity of the injury. The research team advocates for a classification system utilizing all three methods.

"This full range of analysis will make for a more accurate and sophisticated description of the injury that will inform individualized treatment and aid in predicting long-term outcomes more accurately," Korley said.

Delivery and continuity of care for patients with TBI

To many, the "traumatic brain injury" suggests an isolated event. A dramatic scene of a crash victim or wounded soldier receiving lifesaving medical intervention, possibly being cured.

This is a misleading view, Korley says. Think of TBI like COVID-19.

Many people who are hospitalized with the virus do not die, which could be seen as a 'recovery.' But almost half of those people experience significant functional decline after they're discharged. And scores of people with 'mild infection' end up with lingering symptoms of long COVID that can impact their lives.

Like COVID-19, many of those 'recovering' from TBI experience a chronic phase of the injury. However, only 13 to 25% of patients with moderate-to-severe traumatic brain injury end up receiving interdisciplinary inpatient rehabilitation.

"There is the notion that once you leave the hospital after TBI, that's as good as it gets, but it's only the beginning of the battle," Korley said. "The acute phase is when you try to limit secondary brain injury. The chronic phase is a much longer healing process."

For an injury that researchers say is vastly undercounted, they note the United States has no mechanism for long-term TBI care. And for what is available, many survivors do not have, or cannot afford, access.

"Many people actually max out their benefits at that point [of inpatient rehab]," said one TBI patient quoted in the report. "Then when they are home, they have problems and don't have the insurance funds to help with those. To me, it's just criminal that so many victims of TBI are just forced by insurance companies into bed rest, which is just killing their chances of a good recovery."

Korley and the committee recommend creating a national framework for TBI care. They say it should build on the successes of regional trauma systems by establishing local and regional integrated care delivery systems across acute, rehabilitation and recovery phases of the injury. They also want health insurers, Medicare and Medicaid services to offer coverage for TBI care that aligns with clinical guidelines, ensuring equity in access and affordability.

"[Taking these steps] would require a level of continuity and acceptance of responsibility that American health care does not often achieve for chronic illnesses," researchers wrote.

Research and innovation

To date, there is no FDA-approved therapy that can treat damage from traumatic brain injury on its own. Several promising therapies have failed to promote recovery in large clinical trials.

Meanwhile, the committee says research on TBI is feeble compared to other important conditions, such as cancer or heart disease. They called for government organizations -- the National Institutes of Health, the Department of Defense -- and private sector funders to commit to a much larger investment in basic and clinical research to improve the health and well-being of TBI survivors.

Working with the Department of Defense, the Weil Institute for Critical Care Research and Innovation at University of Michigan hosts an annual Massey TBI Grand Challenge, which provides funding for early-stage, innovative and high-risk research to develop the next generation of diagnostics, devices and therapeutics for severe TBI. Researchers make 'Shark Tank'-style pitches to a panel of clinicians and commercialization experts for innovative ways to advance early care. Over six years, 39 teams have been funded with over $4 million awarded.

"This program provides a unique and vital mechanism to bring together diverse expertise from across U-M to propose and develop the almost-science fiction solutions and technologies that will be required to significantly impact the care of victims of TBI," said Kevin Ward, M.D., executive director of the Weil Institute and professor of emergency medicine and biomedical engineering at Michigan Medicine. "The program encourages collaboration across the medical, engineering, basic and computational sciences, and it is really helping us shorten the research and development cycle through strategic de-risking."

Without an entity taking charge to establish clear goals and conduct oversight, experts say, progress is unlikely.

"We want to drive more progress as we create a blueprint for clinicians, researchers and stakeholders who are committed to solving this problem," Korley said. "We are hoping that governmental leaders will pay attention and help redirect funding priorities. A lot of the recommendations we are proposing will take significant funding to implement. This is how our nation will start showing up for survivors of traumatic brain injury, their caregivers and communities."

This activity was supported by Contract No.W81XWH20C0126 between the National Academy of Sciences and the United States Army Medical Research and Development Command of the Department of Defense. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of any organization or agency that provided support for the project. The views, opinions and/or findings contained in this report are those of the author(s) and do not necessarily reflect the views of the United States Army Medical Research and Development Command (USAMRDC).

Story Source:

Materials provided by Michigan Medicine - University of Michigan. Original written by Noah Fromson. Note: Content may be edited for style and length.

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Journal Reference:

1. National Academies of Sciences, Engineering, and Medicine. Traumatic Brain Injury: A Roadmap for Accelerating Progress. Washington, DC: The National Academies Press, 2022; DOI: 10.17226/25394

https://www.sciencedaily.com/releases/2022/02/220201144006.htm

Hepatitis E virus defies alcohol-based hand disinfectants

 The hepatitis E virus (HEV) can cause serious liver inflammation and is the most common cause of acute virus-mediated hepatitis worldwide. Infection can be prevented through appropriate hygiene measures. Scientists from TWINCORE, Centre for Experimental and Clinical Infection Research, the Hannover Medical School (MHH) and the Ruhr Universität Bochum (RUB), together with partners from industry, have investigated the effectiveness of various common hand disinfectants against HEV. They were able to show that most formulations do not completely inactivate the virus.

They have now published these results in the Journal of Hepatology from 24 january 2022.

Infection from pork

In Germany and Europe, HEV has its natural reservoir in pigs. The infection can spread from animals to humans, which is called a zoonosis. This often happens through incompletely heated or raw meat products such as minced meat. In tropical regions of the world, infections occur via contaminated water, sometimes causing large outbreaks. "Some of these infections could possibly be prevented with the right hygiene measures," says Dr. Patrick Behrendt, physician in the Department of Gastroenterology, Hepatology and Endocrinology at the MHH and head of the junior research group "Translational Virology" at TWINCORE. This includes, above all, correct hygienic hand disinfection in everyday clinical practice when dealing with hepatitis E patients and infected animals.

Together with the team of Professor Eike Steinmann, head of the Department of Molecular and Medical Virology at RUB, Behrendt has investigated whether common hand disinfectants can render the virus harmless. "We tested the effect of the alcohols ethanol and propanol, both individually and in the mixing ratios recommended by the WHO, and also commercial hand disinfectants," says Steinmann. "However, only one product that contained another component was effective."

Alcohol alone is not effective

Normally, HEV occurs non-enveloped and, like all non-enveloped viruses, is very resistant to chemical influences. However, virus particles circulating in the blood of patients are surrounded by a lipid envelope. "Not all disinfectants are effective against enveloped and non-enveloped viruses at the same time," says Steinmann. "We used both forms of HEV for our tests."

Although some of the disinfectants tested are certified to inactivate both enveloped and non-enveloped viruses, they were not sufficiently effective against HEV. "The alcoholic components dissolve the lipid envelope, but the resulting "naked" viruses are still infectious," says Behrendt. So HEV is literally hard to break down. The decisive advantage was a product that contains phosphoric acid as well as alcohol. This neutralised all the virus particles sufficiently.

"We were able to show that HEV can resist most common hand disinfectants," says Behrendt. "We hope that these findings will be taken into consideration in the future when hygiene measures are recommended for handling contaminated meat products and in HEV outbreak situations."

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Story Source:

Materials provided by Ruhr-University Bochum. Note: Content may be edited for style and length.

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Journal Reference:

1. Patrick Behrendt, Martina Friesland, Jan-Erik Wißmann, Volker Kinast, Yannick Stahl, Dimas Praditya, Lucas Hueffner, Pia Maria Nörenberg, Birgit Bremer, Benjamin Maasoumy, Jochen Steinmann, Britta Becker, Dajana Paulmann, Florian H.H. Brill, Joerg Steinmann, Rainer G. Ulrich, Yannick Brüggemann, Heiner Wedemeyer, Daniel Todt, Eike Steinmann. Hepatitis E virus is highly resistant to alcohol-based disinfectants. Journal of Hepatology, 2022; DOI: 10.1016/j.jhep.2022.01.006

https://www.sciencedaily.com/releases/2022/02/220201115219.htm

Natural Immunity Lasts For At Least 18 Months: Study

 by Zachary Stieber via The Epoch Times (emphasis ours),

The protection people experience after recovering from COVID-19, known widely as natural immunity, lasts for at least 18 months, according to a recently published study.

Researchers in Italy analyzed the level of antibodies in 36 patients who were documented as contracting COVID-19 in March 2020. About half of the patients went on to get COVID-19 vaccines, but the rest remained unvaccinated. Samples from all but two were tested at timed intervals, ending in September 2021, using assays that have received clearance from the U.S. Food and Drug Administration.

“At 18 months, 97% participants tested positive for anti-NCP, hinting towards the persistence of infection-induced immunity even for the vaccinated individuals,” researchers wrote in the preprint paper, which was published on the medrxiv website.

NCP stands for nucleocapsid, a part of SARS-CoV-2. Antibodies are believed to protect people against against infection from the virus.

“Antibodies against nucleocapsid will be present only in recovered individuals and not vaccinated,” Dr. Asiya Zaidi, a research fellow at the Associazione Naso Sano and one of the authors, told The Epoch Times in an email.

That means even the people who got vaccinated received protection from natural immunity.

Researchers did find that vaccination with Pfizer-BioNTech COVID-19 vaccines gave those with prior infection a significant boost, but that the increase in protection waned relatively quickly.

“Our study findings demonstrate that while double dose vaccination boosted the IgG titers in recovered individuals 161 times, this “boost” was relatively short-lived. The unvaccinated recovered individuals, in contrast, continued to show a steady decline but detectable antibody levels. We do believe that further studies are required to re-evaluate the timing and dose regimen of vaccines for an adequate immune response in recovered individuals,” Zaidi said.

Limitations of the longitudinal observational study include the small number of patients.

The researchers, who fund their own research, said the limited sample size was due to a lack of funding because repeated serology tests for each patient for 18 months was expensive and because following up with all the patients and reminding them of the testing was difficult.

Its strengths include the remarkable length of time.

“This is the longest observation (March 2020-September 2021) for the presence of antibodies against SARS-CoV-2 in recovered individuals along with the impact of 2 dose-BNT162b2 vaccination on the titers,” the researchers wrote.

SARS-CoV-2, also known as the CCP (Chinese Communist Party) virus, causes COVID-19. BNT162b2 is the trade name for the Pfizer jab.

Previous studies have demonstrated the powerful effect of natural immunity against the virus, including a study published in Nature in mid-January that found that the response of memory B cells, a marker of protection against severe COVID-19, evolved in the months following infection “in a manner that is consistent with antigen persistence.”

Other markers of protection were observed in studies in 2021 to last at least over 7 months, at least 8 months, at least 10 months, at least 11 months, at least 13 months, and at least 14 months. The studies were completed before the emergence of the Omicron virus variant, which early data indicate is better at evading both natural immunity and vaccine-derived protection.

https://www.zerohedge.com/covid-19/natural-immunity-lasts-least-18-months-study

Quebec Scraps Planned Tax On Unvaccinated Residents Amid Growing Backlash

 Perhaps seeing the massive response to the Canadian truckers' "Freedom Convoy" this weekend - and, more importantly, their prime ministers' cowering response before he conveniently tested positive for COVID himself just weeks after receiving his booster - was enough to make the provincial government in Quebec rethink its plans to tax any adult who refuses the vaccine.

Plans for the "health tax" have reportedly been scrapped, according to Francois Legault, the premier of the French-speaking province, who made the announcement during a news conference earlier on Tuesday. Even Legault acknowledged that the planned tax had "deeply divided Quebecers."

"Right now we have to build bridges," he added. "To move Quebec forward in a calm social climate, I am announcing that the government will not introduce this bill on the health contribution."

In early January, Legault had announced plans to tax residents who had not yet taken the COVID vaccine, citing a "burden" they were placing on the province’s health-care networks.

"Those who refuse to receive their first dose in the coming weeks will have to pay a new health contribution," Legault said at the time. "I know the situation is tough, but we can get through this together. We need to focus our efforts on two things: Getting the first, second, and third doses of vaccine and reducing our contacts, especially with older people."

As a reminder, Quebec has faced levels of oppression and encroachment on personal liberty that are unmatched anywhere outside of China. /p>

Last week, Quebec’s Health Ministry required "anyone without a vaccination passport must be accompanied at all times by a store employee and cannot purchase products other than those related to the pharmaceutical service they are receiving."

While MSM reports didn't mention them until lower in the story, it's clear the reaction to the Canadian truckers, who held a "Freedom rally" in Ottawa over the weekend, likely contributed to the governor's decision.

Of course, public opinion polling has shown that a majority of Canadians want all COVID restrictions removed, as the Epoch Times has reported.

Meanwhile, RCMP units have reportedly been called in to arrest truckers blocking the border between the US and Canada in Alberta, according to the CBC. Police are reportedly moving in ready to make arrests and seize equipment.

Update (1600ET): The RCMP has reportedly started with "enforcement actions

Although some local towing companies have reportedly refused service.

Monday's announcement marked the second time the Quebec government has walked back public health measures meant to slow the spread of the coronavirus. It also nixed compulsory inoculations for all health care workers last year fearing it would lead to thousands of nurses quitting their jobs, worsening an already severe worker shortage in the sector.

https://www.zerohedge.com/political/quebec-scraps-planned-tax-unvaccinated-residents-amid-growing-backlash