Covid vaccines a shoo-in? Medicine opens Nobel season

 The Nobel season opened on Monday with the pioneers of mRNA Covid-19 vaccines and immune system research tipped for the medicine prize, which kicks off a week of awards against the backdrop of the pandemic.

Breakthroughs in breast cancer, new approaches to rheumatology treatments, as well as research into epigenetics, cell adhesion and antibiotic resistance are also believed to have good chances of winning, experts polled by AFP said.

Two names stand out in particular this year, given the ongoing pandemic: Hungary's Katalin Kariko and Drew Weissman of the United States, pioneers of messenger RNA (mRNA) vaccines and professors at the University of Pennsylvania.

Their discoveries, published in 2005, paved the way for the development of the Pfizer/BioNTech and Moderna vaccines, which have already been injected into more than a billion people worldwide.

The technology has also shown promising results for use against other diseases.

The creator of the prizes, Swedish dynamite inventor Alfred Nobel, laid out in his will that the awards should go to those who have conferred the "greatest benefit to humankind"—making the pair an obvious choice to some.

"It would be a mistake for the Nobel committee not to give the prize to the mRNA vaccine this year, even if it is a bit risky," said Ulrika Bjorksten, head of Swedish public radio's science section.

She noted the pair's work could also be worthy of the Nobel Chemistry Prize, to be announced on Wednesday.

Committee's conservatism

However, many believe the duo—who hold senior positions at German laboratory BioNTech—may have to wait for the accolade.

The various committees tasked with selecting winners for the science prizes are known for allowing years or even decades to pass so that a discovery's true impact can be evaluated before the Nobel is bestowed.

In theory, Nobel's will also specified the prizes should go to work done in the past year, but this has rarely been heeded.

"I don't think it will happen. I just think of the conservatism of the committee's choice. Certainly they would be considered in future years but I'm doubtful for this year," David Pendlebury of Clarivate Analytics, which publishes a list of likely laureates.

Pendlebury said he instead believed the prize would likely go to American Max Cooper, 88, and French-Australian Jacques Miller, 90, for their discovery that white blood cells essential to the human immune system were divided into two categories, B and T lymphocytes.

T-cells have also played a role in understanding immunity to Covid-19.

In 2019, the two received the prestigious Lasker Prize—often seen as a precursor to the Nobel.

But the fact that they have yet to receive a Nobel is widely seen as an anomaly.

"For these two, there must be something we don't know," Pendlebury said.

Other researchers believed to be worthy of a Nobel include pioneers in the field of cell adhesion, such as Japan's Masatoshi Takeichi, US-Finnish scientist Erkki Ruoslahti and British biologist Richard Hynes.

The study of how behaviour and environment can cause changes that affect how genes work—a field known as epigenetics—is also seen as a possibility, with American David Allis and American-Romanian Michael Grunstein mentioned.

In the midst of Covid-19

In the fight against breast cancer, Americans Dennis Slamon and Mary-Claire King could win for identifying risk genes, which has paved the way for treatments.

Another gene specialist, Lebanese-American Huda Zoghbi who discovered the gene responsible for Rett syndrome, is also among potential recipients.

Australian-British Marc Feldmann and Briton Ravinder Maini have also been mentioned for years for having identified the role of a cytokine in rheumatoid arthritis.

The UK's Julian Davies could see also his research into antibiotic resistance, a serious public health issue, given the nod.

While the 2020 award was handed out in the midst of the pandemic, this is the first time the entire selection process has taken place under the shadow of Covid-19.

Nominations closed at the end of January, and at that time last year the novel coronavirus was still largely confined to China.

The 2020 prize did end up going to virus research, albeit the discovery of the Hepatitis C virus.

The Nobel season continues on Tuesday with the award for physics and Wednesday with chemistry, followed by the much-anticipated prizes for literature on Thursday and peace on Friday.

The economics prize winds up the season on Monday, October 11.

This year's Nobels come with a cheque for 10 million Swedish kronor ($1.1 million, one million euros).

https://medicalxpress.com/news/2021-10-covid-vaccines-shoo-in-medicine-nobel.html

Phoenix Biotech Acquisition Prices $155M IPO

 Phoenix Biotech Acquisition Corp. (NASDAQ: PBAXU) (the “Company”), a blank check company formed for the purpose of effecting a merger, share exchange, asset acquisition, share purchase, reorganization or similar business combination with one or more businesses, today announced the pricing of its initial public offering of 15,500,000 units at a price of $10.00 per unit, for gross proceeds to the Company of $155,000,000. The Company's units will be listed on The Nasdaq Global Market (“Nasdaq”) under the symbol “PBAXU” and will begin trading on October 6, 2021. Each unit issued in the offering consists of one share of the Company’s Class A common stock and one-half of one warrant, with each whole warrant exercisable for one share of Class A common stock at an exercise price of $11.50 per share. Once the securities comprising the units begin separate trading, the Class A common stock and warrants are expected to be listed on Nasdaq under the symbols “PBAX” and “PBAXW,” respectively. No fractional warrants will be issued upon separation of the units and only whole warrants will trade. The closing of the offering is anticipated to take place on or about October 8, 2021, subject to customary closing conditions.

Cantor Fitzgerald & Co. is serving as sole book-running manager for the offering. The Company has granted the underwriters a 45-day option to purchase up to an additional 2,325,000 units at the initial public offering price to cover over-allotments, if any. 

https://www.streetinsider.com/Globe+Newswire/Phoenix+Biotech+Acquisition+Corp.+Announces+Pricing+of+%24155%2C000%2C000+Initial+Public+Offering/19027845.html

India to pay $674 compensation for every Covid-19 death

 India's top court has approved the government's decision to pay 50,000 rupees ($674; £498) as compensation for every death due to Covid-19.

The Supreme Court's order followed a petition by lawyers seeking compensation under India's disaster management laws.

India has officially recorded more than 447,000 Covid-19 deaths so far.

However, experts believe that up to 10 times more people could have died in the pandemic.

They have arrived at different estimates after examining excess deaths - a measure of how many more people are dying than would be expected compared to the previous few years.

On Monday Justice MR Shah said the "next of kith and kin of the deceased person" shall be paid this compensation. This would be "over and above the amounts paid by the centre and state under various benevolent schemes", he said.

The court added that the compensation should be paid within 30 days after a family submits an application.

In June, petitioners sought the court's intervention in paying compensation to the families of Covid-19 victims.

They said since Covid-19 was "specially" notified as a disaster under India's National Disaster Management Act, compensation should be paid to the victims.

The 2005 law was enacted for efficient management of disasters, including preparation of mitigation strategies, capacity-building and compensation for lost lives, injuries and damaged properties.

The law says monetary assistance of 400,000 rupees should be paid to family of people who have lost their lives in a disaster.

"We know the government has spent a lot of money in managing the pandemic. But we still think the government should have paid 400,000 rupees compensation to every affected family according to the law. Or they could have given a higher amount to the poor families and less to the well-to do. They could have bettered it," Gaurav Kumar Bansal, one of the petitioners, told the BBC.

According to the federal government, the compensation will be paid "to the next of kin of the deceased due to Covid-19, subject to cause of death being certified as Covid-19" as per the guidelines. The funds for this compensation will be provided by the states.

At least two states - Kerala and Rajasthan - have said the compensation payouts would put pressure on their exchequers, and that the funds should be provided by the federal government.

"You give funds for hailstorm, floods, etc, so you should now add Covid-19 too. It's not that only one state has been affected by it, it's a pandemic," Govind Singh Dotasara, a minister in Rajasthan, told The Indian Express newspaper.

It is not clear yet how much the governments will have to spend on the payout.

In August, the National Disaster Management Authority (NDMA) - which is headed by the prime minister - wrote to the states saying it was not clear how much money should be set aside for compensation as the pandemic had not ended.

It also said that "financial prudence demands that we plan in a manner that assistance can be provided to larger number of people should the number of deaths rise".

Some states like Karnataka have already announced a higher compensation of 100,000 rupees to the families of underprivileged people who died of Covid-19. Sixteen families have already been paid so far, according to a report.

https://www.bbc.com/news/world-asia-india-58731158

4th person dies from rare blood-clotting syndrome after receiving J&J vaccine

 A county in Washington on Tuesday confirmed that a woman died from blood-clotting complications after receiving Johnson & Johnson's single-dose COVID-19 vaccine. She is believed to be the fourth person to have died from such a complication.

King County stated that a female resident in her late 30's had died from the "very rare" complication. The unnamed resident received her J&J shot on August 26.

"Her cause of death was determined to be thrombosis with thrombocytopenia syndrome (TTS), a condition that has been identified as a rare but potentially serious adverse event in people who received the J&J vaccine," the county said in a statement.

When reached for comment The Hill, Johnson & Johnson said in a statement:

"The safety and well-being of every individual who receives a Johnson & Johnson product remains our top priority. Any adverse event report about individuals receiving Johnson & Johnson’s single-shot COVID-19 vaccine, as well as our own assessment of the report, is shared with the U.S. Food and Drug Administration (FDA), European Medicines Agency, the World Health Organization (WHO) and other appropriate health authorities where our vaccine is authorized."

The company added that it is in support of raising awareness of the signs of the rare side effect in order to "ensure they can be quickly identified and effectively treated.

Earlier this year, administration of the J&J vaccine was briefly paused while U.S. health officials reviewed the rare blood clotting complication. Such complications relating to the J&J vaccine appear to be more common in women than in men.

Officials ultimately determined that the benefits offered by the J&J shot outweigh the risks and states resumed administering the vaccine in April.

King County noted that women aged 18-49 are at a higher risk for complications than women aged over 50. However, regardless of age, the county added that the benefits still outweighed the risks of not getting inoculated.

J&J scientists also said in April that there was “insufficient” evidence of there being a “causal relationship” between the company's COVID-19 vaccine and the reported complications.

According to the Centers for Disease Control and Prevention, nearly 15 million doses of J&J's coronavirus vaccine have been administered in the U.S. so far.

A similar complication was seen with the AstraZeneca COVID-19 vaccine, with numerous countries in Europe opting to stop administering it . Other countries such as the U.K. decided to limit the AstraZeneca vaccine to people over 30 as younger people were believed to be more susceptible to complications.

AstraZeneca's vaccine has not been approved for use in the U.S.

https://thehill.com/policy/healthcare/575417-fourth-person-dies-from-rare-blood-clotting-syndrome-after-receiving-jj

What we know — and don’t know — about Merck’s new Covid-19 pill

 The announcement that a pill from Merck and partner Ridgeback Biotherapeutics kept Covid patients out of the hospital made headlines and moved stocks late last week. But as is so often true when data are released by press release, there are still many questions left unanswered.

Doctors are excited about the medicine, molnupiravir, because a regimen of pills, even one that involves taking several pills twice a day for five days, should be far easier to deliver to patients than current antiviral Covid-19 treatments, which must be given intravenously. But it’s still unclear how widely this treatment will be used. There will also be debate among financial analysts at investment banks regarding exactly how many billions of dollars in sales the new drug will generate.

Here are some things to keep in mind as we learn more about molnupiravir and about other Covid-fighting pills in development at other companies.

How many other anti-Covid pills will end up proving effective?

One of the reasons that the success of molnupiravir is such a big deal is that there were questions as to whether an antiviral pill could help Covid-19 patients if given early enough. This medicine certainly did, reducing hospitalizations by 50%; it also appeared to have an impact on whether patients survived. That makes it a game-changer. Its success also ups the odds that other medicines will prove effective, too.

Results for other drugs are likely to be released by the end of the year. That includes data about a similar pill, also given as a five-day course, from Atea Pharmaceuticals and Roche, and about a pill developed by Pfizer that is from a different drug class and might be combined with molnupiravir.

Another positive note for all these drugs: remdesivir, the intravenous antiviral made by Gilead Sciences, also showed positive results when used for three days after onset of symptoms. That’s not practical — it had to be given via IV for three days — but bodes well for antiviral pills showing some efficacy. It’s even possible those pills might be combined.

How safe is molnupiravir?

Obviously, a drug given early in Covid needs a clean safety profile. So far, the data included in the press release look very good. Patients in the placebo arm were three times more likely to withdraw from the study due to apparent side effects than those who actually received molnupiravir. That likely means the side effects of Covid were worse than those of the drug.

But only so much can be seen from that kind of data. Molnupiravir works by messing up the way the virus copies RNA, its genetic material, preventing viral replication. There is some concern it could be mutagenic, meaning that it could cause mutations. One result could be that it causes birth defects. In the clinical trial, both women and men were told to either abstain from sexual intercourse or to use contraception while they were taking the drug and for at least four days after. Women of childbearing age also needed a negative pregnancy test to start taking the medicine.

Could there be other effects? In a conference call with reporters Friday, Daria Hazuda, a top Merck virologist, said that Merck and Ridgeback had studied the mutagenic potential of the drug in both cell lines and in animal models that are routinely used in drug development and which are accepted by regulatory agencies.

“I would say that in all of the models where we have looked, we have seen no evidence of the potential for mutagenicity for this agent,” Hazuda said. “We’re very comfortable that the drug will be safe if used as intended and at the concentrations where we have looked and in the concentrations which we are achieving in patients.”

Will molnupiravir be used only in unvaccinated patients?

Merck’s trial was conducted entirely in patients who had not been vaccinated. That made it much easier to show that the medicine can reduce hospitalization and death — because patients who have not previously been vaccinated are more likely to be hospitalized or die.

But does that mean that, in practice, the drug will only be used in unvaccinated patients, or will it be used in cases of breakthrough infections? It’s hard to say. Patients with breakthrough infections are at lower risk of hospitalization, which could change the risk-benefit calculus around the medicine.

So how big will the market be?

Daina Graybosch, an analyst at SVB Leerink, forecast in a note to investors on Monday morning that molnupiravir sales will peak near $5 billion a year in 2022.

Built into this are a number of assumptions, among them that the first-mover advantage will mean that Merck and Ridgeback will be used more than the other pills in development and that vaccinated patients with breakthrough infections will be eligible to receive the drug, too.

Timothy Anderson of Wolfe Research, a standalone equities research firm, takes the other side, essentially saying it is too soon to put a number on molnupiravir sales, in part because data from competing firms are not available but also because other questions remain.

“Vaccination rates continue to rise in the US and other developed markets, meaning the cohort of patients who would qualify for molnupiravir (i.e. mostly those who are unvaccinated, at higher risk) will shrink over time,” Anderson wrote in a note to clients.

Successfully using the drug, he pointed out, will also require that patients get tested early in their disease course. If people start to skip getting tested, they won’t receive molnupiravir.

What will it cost and who will pay?

Most analysts are basing the cost of molnupiravir on the $1.2 billion the U.S. government spent to lock up 1.7 million courses of the medicine, which works out to $700 per five day course. But Anderson points out that the cost for a new pill to treat influenza developed by Roche is just $150 per course. Will the $700 price hold up?

Questions about payment and distribution could play a big role in how big the market for molnupiravir gets. Anderson assumes in his note to clients that, in the U.S., insurance companies will be paying for the drug through traditional channels. He expects that at $700, insurers will restrict use of the drug to those who are unvaccinated and have multiple risk factors for disease — basically similar profiles to those who are in the trials.

But it’s also possible that sales in the U.S. might be mostly to the government. This is how things have worked with both remdesivir, used in hospitalized patients, and the monoclonal antibodies developed by Regeneron and Eli Lilly. Will the government handle the distribution of a pill granted an emergency use authorization in the same way that it has handled the monoclonals?

How will the availability of Covid pills affect vaccines and other treatments?

It doesn’t make any sense to forego a Covid vaccine because a pill to treat the disease exists. The benefits are additive, and someone who got a breakthrough infection and then the pill has a much lower risk of hospitalization than someone who just relied on the pill.

But it seems likely that some people will feel less urgency to get vaccinated as a result of molnupiravir’s existence, and shares in Pfizer, BioNTech, and Moderna all fell on Friday. The latter two are down again Monday morning.

Shares in Regeneron also fell, as oral drugs create uncertainty for its monoclonal antibody treatment for Covid. The landscape there is uncertain, with other companies coming forward with antibodies that may have advantages. One small firm, Adagio Therapeutics, recently presented early data on an antibody it thinks could be given as a single shot.

How does this treatment relate to ivermectin?

This is simple: it doesn’t. But it’s worth taking a look at what data are available for each.

Ivermectin, ironically, is another Merck drug. The company’s donation of the medicine to be used to combat a parasitic disease called river blindness is one of the great examples of pharmaceutical philanthropy. It’s also used as a veterinary drug to treat heartworm.

Early in the pandemic, there were studies in cell cultures that showed that ivermectin and another drug, hydroxychloroquine, might be worth testing as Covid-19 treatments. Multiple studies have failed to show a benefit for hydroxychloroquine, but the picture is murkier for ivermectin. Still, one of the largest studies showing a benefit was withdrawn due to widespread flaws.

There is a study conducted in Brazil, the Together Trial, that tested a three-day course of ivermectin compared to placebo and showed there was no benefit on hospitalizations and ER visits. That would make it unlikely that ivermectin, an old antiparasitic, would have efficacy approaching this newer antiviral.

Drug companies are unlikely to conduct large, rigorous studies of older generic medicines — although Novartis did begin, then stop, a hydroxychloroquine study. But right now it is unlikely that ivermectin is the oral Covid medicine the world needs. Molnupiravir, on the other hand, might be.

https://www.statnews.com/2021/10/04/what-we-know-and-dont-know-about-mercks-new-covid-19-pill/

Ex-FDA officials ask SCOTUS to take up J&J talc case

 Eight former FDA officials, including former FDA commissioner Andrew von Eschenbach and multiple deputy commissioners, submitted an amicus brief to the Supreme Court yesterday — asking for the Court to review the Mississippi Supreme Court decision that ruled against J&J earlier this year.

Mississippi’s complaint in 2014 accused the mega-company of violating consumer protection laws by not disclosing ovarian cancer risks to women posed by its baby powder containing talc.

J&J sought summary judgment in its appeal to the court, arguing the Mississippi Consumer Protection Act doesn’t apply to the labeling of products regulated by the federal Food and Drug Administration. The Mississippi Supreme Court disagreed, and affirmed a lower court’s previous ruling.

The former officials argue that notice-and-comment rulemaking, which the FDA officials say is rarely used, subverts and upends the FDA’s system and authority over labeling.

“By stripping the FDA’s labeling decisions of preemptive effect unless they first undergo notice-and-comment rulemaking, the decision leaves the agency with an impossible choice: sacrifice the flexibility it needs to oversee thousands of products in an ever-shifting market, or allow its scientifically sound warnings to be crowded out by conflicting state-imposed labels,” the officials wrote.

The ex-officials further reiterated that the FDA lacks time and resources to run every decision through notice-and-comment rulemaking.

“According to the Mississippi Supreme Court, that reality means FDA must share labeling authority with all 50 states, any one of which can require a label specifically rejected by FDA as scientifically unsound,” the officials wrote.

Ultimately they want the Supreme Court to “clarify the law of preemption and prevent the Mississippi Supreme Court’s decision from disrupting FDA’s vital functions,” the writers said.

https://endpts.com/ex-fda-officials-ask-scotus-to-take-up-j-annovis-shows-data-from-phii-parkinsons-trial/

Supreme Court Won't Rule on Governor's Pandemic Authority

 The U.S. Supreme Court decided Monday against hearing an appeal of a decision that found Gov. Charlie Baker did not overstep his authority with sweeping orders to close businesses and limit gatherings to control the coronavirus early in the pandemic.

The nation's highest court announced without comment Monday that it would not consider the appeal.

The lawsuit argued that Baker had no authority to issue public health-related orders under the state's Civil Defense Act, which it said was designed to protect the state from foreign invasions, insurrections, and catastrophic events like hurricanes and fires.

The Massachusetts Supreme Judicial Court, the state's highest court, in December rejected the challenge, brought on behalf of a group including salon owners, pastors and the headmaster of a private school. They accused the Republican governor of exercising "legislative police power" by declaring a state of emergency under the Civil Defense Act.

The Massachusetts court said the pandemic clearly merited action by the governor under the Cold War-era law. It also rejected the lawsuit's argument that the governor's actions infringed on people's constitutional rights to due process and free assembly.

"Given that COVID-19 is a pandemic that has killed over a million people worldwide, it spreads from person to person, effective vaccines have not yet been distributed, there is no known cure, and a rise in cases threatens to overrun the Commonwealth's hospital system, it is a natural cause for which action is needed," the Massachusetts court stated in its December ruling.

The governor declared a state of emergency March 10, 2020, giving him greater power to take actions like shutting down events with large gatherings of people or gaining access to buildings or stockpiling protective gear.

He went on to issue a slew of emergency orders prohibiting gatherings of a certain size, closing certain businesses and mandating masks aimed at slowing the spread of the disease in the hard-hit state.

More than 18,200 Massachusetts residents have died from COVID-19 since the start of the pandemic.

https://www.medscape.com/viewarticle/960209