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Friday, February 5, 2021

Sanofi eyes mores savings, higher profitability after earnings rise

 Sanofi said on Friday it aimed to grow earnings per share this year after it posted stronger-than-expected results in the fourth quarter, and the drugmaker committed to boosting cost savings and profitability further through to 2025.

The French firm, which stunned investors last year with the delay of a COVID-19 vaccine candidate, confirmed an operating income margin target of 30% for 2022 and set itself a goal to improve it to more than 32% three years later.

The company is hosting a virtual investor day later on Friday that will largely focus upcoming drugs.

https://www.reuters.com/article/sanofi-results/sanofi-eyes-mores-savings-higher-profitability-after-earnings-rise-idUSL8N2KA6SU

Pfizer Confirms U.S. Patent Term Extension for IBRANCE tol March 2027

 Pfizer Inc. (NYSE: PFE) today announced that the U.S. Patent and Trademark Office (USPTO) recently issued a U.S. Patent Term Extension (PTE) certificate for IBRANCE® (palbociclib). The certificate extends the term of U.S. Patent No. RE47,739 (‘739) by more than four years until March 5, 2027. The PTE certificate was granted under the patent restoration provisions of the Drug Price Competition and Patent Term Restoration Act of 1984.

https://www.businesswire.com/news/home/20210205005079/en/Pfizer-Confirms-U.S.-Patent-Term-Extension-for-IBRANCE%C2%AE-palbociclib-Until-March-2027

Spero Therapeutics: FDA Hold on SPR720 Phase 2a Trial

 Spero Therapeutics, Inc. (Nasdaq: SPRO), a multi-asset clinical-stage biopharmaceutical company focused on identifying, developing and commercializing treatments in high unmet need areas involving multi-drug resistant bacterial infections and rare diseases, today announced that the United States Food and Drug Administration (FDA) informed Spero that a clinical hold has been placed on its Phase 2a clinical trial of SPR720, Spero’s investigational oral antimicrobial agent being evaluated in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD).

Spero received verbal notification of the clinical hold for the SPR720 Phase 2a trial but has not yet received written notice from the FDA. The clinical hold follows the notification by Spero to the FDA of its decision to pause dosing in its ongoing Phase 2a clinical trial of SPR720 as a precautionary measure following events in its ongoing animal toxicology study of SPR720. The decision to implement the pause was made based on a recommendation from Spero’s Safety Review Board (SRB), following review of data from an ongoing toxicology study of SPR720 in adult non-human primates in which mortalities with inconclusive causality to treatment were observed. The animal study is being conducted to assess the potential toxicity of SPR720 over a 4-month duration. A concurrent 4-month study of SPR720 in rats is proceeding uneventfully. These studies are meant to support longer-term treatment with SPR720 beyond the 28 days currently supported by IND-enabling toxicology studies. Spero is in discussion with FDA to evaluate the findings and determine the further development pathway for the SPR720 clinical program. No serious adverse events have been observed in any human study participants.

https://www.globenewswire.com/news-release/2021/02/05/2170670/0/en/Spero-Therapeutics-Provides-Update-on-SPR720-Phase-2a-Clinical-Trial.html

Pfizer withdraws application for emergency use of its COVID-19 vaccine in India

 Pfizer Inc has withdrawn an application for emergency-use authorization of its COVID-19 vaccine in India that it has developed with Germany’s BioNTech, the company told Reuters on Friday.

The U.S. company, which was the first drugmaker to apply for emergency use authorization of its COVID-19 vaccine in India, had a meeting with the country’s drugs regulator on Wednesday and the decision was made after that, the company said.

“Based on the deliberations at the meeting and our understanding of additional information that the regulator may need, the company has decided to withdraw its application at this time,” it said in a statement to Reuters.

“Pfizer will continue to engage with the authority and re-submit its approval request with additional information as it becomes available in the near future.”

Pfizer had sought authorisation for its vaccine in India late last year, but the government in January approved two much cheaper shots - one from Oxford University/AstraZeneca and another developed at home by Bharat Biotech with the Indian Council of Medical Research. Both companies had applied for approval of their vaccines after Pfizer.

India’s Central Drugs Standard Control Organisation had declined to accept Pfizer’s request for approval without a small local trial on the vaccine’s safety and immunogenicity for Indians, Reuters has reported.

Indian health officials say they generally ask for so-called bridging trials to determine if a vaccine is safe and generates an immune response in its citizens whose genetic makeup can be different from people in Western nations. There are, however, provisions under India’s New Drugs and Clinical Trial Rules, 2019, to waive such trials in certain conditions.

Pfizer earlier told Reuters its application was supported by data from a global study that showed an overall efficacy rate of 95% with no vaccine-related, serious safety concerns.

https://www.reuters.com/article/health-coronavirus-india-pfizer/exclusive-pfizer-withdraws-application-for-emergency-use-of-its-covid-19-vaccine-in-india-idUSL4N2KB1NZ

Palihapitiya-backed Clover Health gets notice of SEC probe

 Chamath Palihapitiya-backed Clover Health Investments said Friday it received a notice of investigation from the Securities and Exchange Commission and that it intends to cooperate.

Clover, however, pushed back against a critical report from short-selling specialist Hindenburg Research, saying some claims in the report were “completely untrue.”

On Thursday, Hindenburg published a scathing report that called Clover Health a “broken business,” sending the insurance firm’s shares down more than 12%, their biggest daily percentage drop in four months. Shares of Clover rose more than 3.5% in premarket trading Friday after the company published its response. Hindenburg, which has a history of publishing short-selling research, said Thursday it does not hold a position in Clover.

Hindenburg also said Clover was under investigation from the Department of Justice and that the investigation was not disclosed to investors. In its response to the Hindenburg report, Clover said it has received inquiries from the DOJ but did not believe the inquiries were material to its investors. The company characterized the DOJ inquiries as standard practice since Clover works with the Medicare system.

Clover said it decided it did not need to disclose the DOJ inquiries after consultation with its lawyers. The company did not say what the DOJ’s inquiries were about. On the SEC side, Clover said it received the letter from the agency on Thursday following the publication of Hindenburg’s report. The company said it was unware of any investigations outside of the letter from the SEC it received Thursday.

The DOJ on Thursday declined to comment on any potential investigations or inquiries related to Clover. The SEC declined to comment on Friday.

In addition to the alleged investigations, Clover responded to Hindenburg’s critique of a separate company that shares investors and governance with Clover called Seek Insurance. Hindenburg alleged Seek Insurance, a site designed to help people find Medicare plans, doesn’t disclose its relationship to Clover even though its website characterizes itself as an unbiased platform for choosing a health plan. Clover said in its response that Seek Insurance is an affiliate of Clover, but is still independent start-up.

Clover also said Seek’s website would be updated soon with more information, and published a breakdown of the plans Seek customers choose. According to Clover, 13.5% of Seek customers chose a Clover plan, behind CVS/Aetna (17%), Humana (20%) and Cigna (20%).

Finally, Clover addressed Hindenburg’s allegations that the company’s software prompts doctors to charge the Medicare system more than necessary, a practice called “upcoding.” Hindenburg said Clover’s software encourages upcoding with “irrelevant diagnoses” to “deceive” and charge the Medicare system more. Clover denied those allegations in its response, and said doctors receive a flat payment for office visit, and that it’s up to the doctor to choose the diagnosis.

You can read all of Clover’s lengthy, point-by-point response to Hindenburg here.

https://www.cnbc.com/2021/02/05/chamath-palihapitiya-backed-clover-health-gets-notice-of-sec-investigation.html

Merck KGaA to boost lipid supply to vaccine maker BioNTech

 Germany’s Merck KGaA said on Friday it would boost its supply of lipids, a key ingredient in messenger RNA COVID-19 vaccines, to biotech firm BioNTech.

“Merck, in close collaboration with BioNTech, will significantly accelerate the supply of urgently needed lipids and increase the amount of lipid delivery towards the end of 2021,” Merck said in a statement.

Lipids, mainly in the form of lipid nanoparticles, are used to encapsulate and protect messenger RNA molecules to help them reach the designated cells in the human body.

https://www.reuters.com/article/merck-biontech-lipids/merck-kgaa-to-boost-lipid-supply-to-vaccine-maker-biontech-idUSFWN2KA1OP

Thursday, February 4, 2021

Op-Ed: Do 'Lockdowns' Work? — And, if so, how much?

 In response to the COVID-19 pandemic, there have been thousands of specific policies instituted around the globe. At times, restrictions have been big and bold. Recently, the city of Perth, Australia, was placed in "lockdown" after a single case of SARS-CoV-2. Other restrictions have been focused: removing swings from playgrounds, capping the number of dining guests, or limiting the time for meals (90 minutes). One Toronto suburb closed outdoor ice-skating rinks, toboggan hills, and dog parks. The sheer variety of restrictions meant to curb the spread of SARS-CoV-2 raises an important question: which ones work? And how big are their effects?

I suspect that for many restrictions -- perhaps even most restrictions -- we will never know. We will never know, for instance, if removing the rim from a basketball hoop or closing a toboggan hill slowed SARS-CoV-2 where these strategies were deployed. For larger interventions -- mandatory business closure and stay at home orders, colloquially called "lockdowns" -- we may someday have a scientific consensus as to whether and to what degree this practice changes viral spread, but I believe that day is years away. Here, I wish to highlight challenges with understanding these interventions.

Challenges with identifying the effect of lockdowns

Already some studies have yielded mixed results. One analysis has found that mandatory business closure and stay-at-home orders were not associated with a reduction in infections. Another analysis did find a reduction. Both have limitations. Allow me to highlight some challenges that most research on this topic will face.

First, lockdown is not expected to yield immediate results. One has to account for the typical lag before an effect can realistically show up, but this introduces analytic flexibility. Should we look for effects 7 days later, or 5 or 15? If we look too soon, we might get the wrong idea. An intervention that slows viral spread may appear to lead to viral spread, because we deployed it on the upslope (reverse-causation). Alternatively, if we lag the analysis too much, we might see the impact of other interventions or the natural shape of the pandemic curve.

Second, places often institute multiple restrictions concurrently, alongside powerful media messages to the public. In other words, was it the business closure that helped, the fact the nightly news scared people, or was it another restriction that occurred at the time of (or close to) the business closure that changed outcomes?

Third, there are many ways to define "lockdown"; many regions, municipalities, or countries to include or exclude; many ways to model the data; and many investigators who will probe the dataset. Put this together, the range of "answers" is certain to vary widely. A team from Edmonton, Alberta, defining lockdown as all business closures of more than 3 days, and looking at the county level data for 12 countries might get a different "answer" than a group from Boston defining lockdown as any nonessential business closure, and looking at national data from 82 countries. Already we see a hint of the variety of answers that may be generated. In the long term, I am hopeful that somewhere in this sea of data, there may be a natural experiment that analysts can take advantage of to provide some clarity.

'Lockdown' is not like an aspirin

Fourth, restrictions might be even more complicated. A lockdown is not like an aspirin. It may not exert the same effect every time it is deployed. Lockdowns might have different effects based on the case rate. Lockdowns might help when cases are just a handful, as in Perth, in an effort to drive them to zero. Or lockdowns might only work when case rates are modest (1 case per 10,000 residents). Alternatively, lockdowns might work when case rates are brisk (1 per 1,000 residents). Perhaps lockdowns work in none of these cases, or just the first and second scenario. In other words, the effect of lockdowns may depend on the rate or absolute number of cases, or many other biologic factors (e.g., population density).

Fifth, the same lockdown in the same location with the same enforcement may have diminishing effects. If people are feeling a sense of purpose and camaraderie, there may be a positive effect, but if those same people feel distrustful or fatigued, there may be a negative one. Lockdowns depend on the buy-in of the populace. The desire to isolate yourself wanes over time. What worked in April might not work in November.

Sixth, lockdowns might have different effects based on the culture of the region, the practices of bordering nations, household density, or the political climate. What works in Norway might not work in the U.S. What works in New Zealand might not work in Canada.

Seven, lockdowns depend on media coverage. Previously I alluded to the fact that it will be challenging to separate the effect of lockdown policies from the fact that the media coverage of COVID naturally encourages people to hunker down. Here, consider that lockdowns might work better when media coverage is lax, but less so when it is frenetic. Because in the latter case, the additional people who change behavior due to the mandate may be few.

Eight, lockdowns depend on specific behaviors that drive spread. In a region where daily interactions are driving spread, lockdowns may work. In a region where all spread occurs in a meat processing plant, the same lockdown may have no effect if the plant remains in operation.

These considerations are just a few of the methodologic challenges with figuring out whether lockdowns work. And they do not even touch the harder question of: what are the complete effects of lockdown? What is the effect of restrictions on educational, mental health, cardiovascular, and other societal outcomes? And, when do these occur?

Finally, I must mention that some may frame this entire discussion differently. They may start with the premise that the goal of policies is to separate people to prevent spread, and consider lockdowns alongside all other measures. I support research efforts to examine the question in this manner as well.

I wish this discussion captured all the complexity to lockdowns, but there is one more factor that must be considered. In cancer medicine, methotrexate is an effective drug, but you often have to give leucovorin to overcome the devastating side effects. Similarly, a lockdown might have one set of effects in a nation with a strong social safety net, or strong unemployment insurance, and a different set of effects in a nation with a tattered safety net, and no unemployment insurance. Resources are the antidote to lockdown, and resources are not evenly distributed or deployed. All studies of lockdowns should account for varying resources.

This discussion has just been about one class of restriction or rule, but what about closing playgrounds, or removing swings, or closing ice rinks, or the many other specific policies implemented. For some of these interventions, I believe the plausibility is low. It is unlikely -- on the face of it -- that closing playgrounds will substantively curb viral spread, and these have met fierce opposition. A future society may look back critically on many of these policies. For many other policies, we may never know whether they helped or hurt.

Pundits need humility

When I think about the past year, and the thousands of interventions we deployed to combat the coronavirus, I am saddened to know we will end with very little idea of which specific interventions helped, which hurt, and which were neutral. Imagine you ran a multi-trillion-dollar study and you didn't get any answer at all.

Going forward, we must be more thoughtful in applying restrictions. Municipalities should avoid throwing the kitchen sink at once. Implementing things in sequence, with time between policies, can help disentangle which policies help and which do not.

Coordinated action can help. If 20 municipalities work together, and 10 try a set of some interventions and 10 others try different ones, we may start to learn which work, and to what degree. Repeating this experiment is the path to knowledge.

Next, with restrictions must come resources. Each policy meant to curb the spread of the virus may have harmful side effects. These harms must be measured and documented. Right now, we know little about how restrictions affect people, particularly poor and vulnerable ones. Resources can be applied to mitigate these harms. Folks concerned with the downsides of lockdown should not be demonized, ostracized, and marginalized. We must engage with them.

Pundits must have humility. Each day on Twitter, I see doctors, epidemiologists, or policy experts definitively proclaim what we ought to do. These comments often prompt fierce backlash from folks equally confident that these interventions hurt. The truth is there is massive uncertainty and being honest about that might make for more productive conversations and compromise.

Lastly, policymakers must be upfront with the public as to the goals of intervention and under what circumstances the restrictions can be relaxed. Specific benchmarks for when and how policies are deployed and when they can be eased must be posted for public view in advance of deployment.

Finally, we must not confuse matters of science with matters of morality. Most people want to minimize suffering and death, and disagreements are about how to do so, not the goal. Whether and to what degree restrictions work and under what circumstances is a set of scientific questions. Let me be the first to admit that I simply do not know the answers. Moreover, I believe the real answers will take years to emerge. As is often the case in life, distance brings wisdom.

Vinay Prasad, MD, MPH, is a hematologist-oncologist and associate professor of medicine at the University of California San Francisco, and author of Malignant: How Bad Policy and Bad Evidence Harm People With CancerThe views expressed above are his own and not his institution's.

https://www.medpagetoday.com/blogs/vinay-prasad/91054