'Double mutant' coronavirus variant surfaces in SF Bay Area

 The Bay Area has yet another coronavirus variant to contend with.

Through genomic sequencing, the Stanford Clinical Virology Lab has identified and confirmed one case of an emerging variant that originated in India, according to lab director Dr. Benjamin Pinsky. The lab is screening seven other presumptive cases and should have the results early this week, he said.

According to Pinsky and news reports, the confirmed case is a patient from a Stanford Health Care clinic and likely occurred in Santa Clara County. County health officials said they are not yet monitoring the new variant because it is not yet on the Centers for Disease Control and Prevention’s list of concern.

The variant is being dubbed the “double mutant” because it carries two mutations in the virus that helps it latch itself onto cells. It could possibly be responsible for the troubling new surge in cases in India. It is not yet known if the variant is more infectious or resistant to vaccine antibodies.

Peter Chin-Hong, an infectious disease expert at UCSF, said it appears the variant could be more infectious because it accounts for 20% of cases in the heavily hit state of Maharashtra. Chin-Hong said cases have increased more than 50% there in the past week.

“It also makes sense that it will be more transmissible from a biological perspective as the two mutations act at the receptor binding domain of the virus, but there have been no official transmission studies to date,” he wrote in an email.

One of the mutations, E484Q, is similar to the E484K mutation found on both of the variants first detected in Brazil and South Africa. The other mutation, L452R, is also found in a variant first detected in California. Pinsky said both mutations could possibly reduce neutralization by antibodies, therefore making vaccinations less effective against the strain.

“This Indian variant contains two mutations in the same virus for the first time, previously seen on separate variants,” Chin-Hong said. “Since we know that the domain affected is the part that the virus uses to enter the body, and that the California variant is already potentially more resistant to some vaccine antibodies, it seems to reason that there is a chance that the Indian variant may do that too.”

He said so far no studies have confirmed any of this. Still, Chin-Hong said it appears this variant may be more regional, as the B.1.1.7 variant that originated in the U.K. is the more dominant strain in India. And while it’s not certain if the variant is resistant to vaccines, he is “optimistic” that vaccinations will work given what is known about their efficacy against the variants originating from South Africa and California.

The latest discovery adds to the list of worrisome variants that have made their way to the U.S., including the widely spreading B.1.1.7. variant, which is 50% more infectious. The P.1 strain that originated in Brazil and a variant from South Africa have both been found in the Bay Area, and both are believed to be somewhat resistant to vaccines.

There are many cases statewide of the variants originating in California that are more infectious and could possibly be resistant to vaccines, and ones from New York identified in Santa Clara County that could also be potentially vaccine-resistant.

Pinsky said there is still much to be learned about the variant from India, but nobody should panic, especially because case numbers are down in California and large numbers of people are getting vaccinated.

“It’s important for us to continue to monitor the emergence of these variants,” he said. “The point is to keep getting vaccinated and to keep monitoring for the emergence of variants. I don’t think it is of significant concern yet. We just have to be vigilant.”

https://www.sfchronicle.com/local/article/Double-mutant-coronavirus-variant-surfaces-16076361.php

DeSantis spars with '60 Minutes' over vaccine rollout

 Florida Gov. Ron DeSantis (R) sharply shot down reporting by "60 Minutes" alleging he funneled the state's coronavirus vaccines to rich communities and privatized the vaccine rollout to benefit donors while many minorities in the state struggle to obtain access to an inoculation. 

CBS reporter Sharyn Alfonsi presented a far-ranging report for "60 Minutes" Sunday evening critical of Florida's vaccine rollout. Among other allegations, Alfonsi said DeSantis gave a contract to distribute coronavirus vaccines to the grocery store chain Publix after Publix made a $100,000 donation to his political action committee.

DeSantis declined a request for an interview, Alfonsi said, but she caught up with him at an event south of Orlando.

"Publix, as you know, donated $100,000 to your campaign and then you rewarded them with the exclusive rights to distribute the vaccine in Palm Beach," Alfonsi told the governor. 

"So first of all what you're saying is wrong," DeSantis replied. "That's a fake narrative. ... I met with the county mayor. I met with the administrator. I met with all the folks in Palm Beach County and I said, 'Here's some of the options. We can do more drive-thru sites. We can give more to hospitals. We can do the Publix.' And they said, 'We think that would be the easiest thing for our residents.'"

Alfonsi pressed DeSantis, saying his critics say the inequitable vaccine distribution and awarding of the contract to the grocery store to distribute the vaccine amount to a "pay for play" scheme. 

"It's wrong, it's a fake narrative," DeSantis said. "I just disabused you of the narrative and you don't care about the facts because obviously I just laid it out for you in a way that is irrefutable. So clearly it's not." 

Alfonsi attempted to chime in again, but DeSantis shouted over her: "No, no, no, you're wrong, you're wrong, you're wrong." 

Publix told "60 Minutes" there is no connection between the supermarket chain's campaign contributions and its partnership with the state to administer the vaccine.

State Rep. Omari Hardy (D) told "60 Minutes" DeSantis's decision to privatize the vaccine rollout has not worked for people of color in the state. 

She pointed to one low-income community without a Publix, meaning its residents, including elderly residents, would need to travel almost 30 miles to get a vaccine.

"Before, I could call the public health director. She would answer my calls. But now if I want to get my constituents information about how to get this vaccine, I have to call a lobbyist from Publix? That makes no sense," Hardy said. "They're not accountable to the public." 

The accusations regarding Publix come as DeSantis is already under fire for Florida's vaccine rollout. He's been accused of funneling vaccine doses to wealthy, white communities and steering pop-up vaccine sites to communities associated with political donors.

https://thehill.com/homenews/state-watch/546408-desantis-spars-with-60-minutes-over-vaccine-rollout-what-youre-saying-is

Renewed push to delay second Covid vaccine

 As Covid-19 cases spike and coronavirus variants continue to spread, the Biden administration is facing renewed calls to delay second vaccine doses and blanket more of the U.S. population with an initial shot.

Advocates of a strategy focused on first doses include Democratic and Republican senators, Trump administration surgeon general Jerome Adams, and at least four physicians or epidemiologists who advised President Biden on pandemic response issues prior to his inauguration, including the prominent surgeon and author Atul Gawande.

Despite the new advocacy, and its own warnings of “impending doom,” the Biden administration has given no indication it will budge. But the shift in opinion underscores the growing alarm at a possible fourth wave of U.S. Covid-19 cases — and frustration with the federal government’s lack of flexibility.

We need to get 50 million more people vaccinated as fast as we can,” said Zeke Emanuel, the physician who served as a key Obama administration health adviser and sat on President Biden’s pandemic advisory board during the transition. “We could get there in the next two and a half or three weeks if we focus on giving everyone one dose. I think we’re missing another opportunity.”

Gawande wrote this week that the Biden administration should delay second vaccine doses until 12 weeks following the first dose, as opposed to the current three- or four-week interval. Two other members, Emanuel and Michael Osterholm, have argued for delaying second doses since February. A fourth, Céline Gounder, recently announced she was reconsidering her stance after months of vocally opposing the strategy.

The latest push comes as U.S. case rates have begun to tick upward, and as some states, including Michigan, have begun to experience a surge in hospitalizations reminiscent of July 2020 and January 2021. The U.S. has reported roughly 60,000 new cases per day for the last week, far below the country’s January peak but similar to last summer’s surge.

The Biden administration has stayed the course despite new evidence suggesting that even a single dose of the vaccines manufactured by Moderna or the Pfizer-BioNTech partnership is highly effective at reducing Covid-19 infections. Risk of infection, according to a recent study, falls by 80% two weeks after an initial shot. The figure increases to 90% two weeks after a second dose.

A growing number of public health experts have used the new data to argue that the strategy is clear-cut. In the short term, they contend, giving twice as many people 80% protection against the virus would do dramatically more to stop the spread than giving the current number 90% protection.

Other countries have already employed the delayed-dose strategy, with varying results. It has been highly successful in the United Kingdom, which has deployed the tactic with Pfizer-BioNTech’s and AstraZeneca’s vaccines, extending the interval between doses there to 12 weeks. Already, 47% of citizens have received at least one dose. Though only 7% of the population is fully vaccinated, daily case rates there have plummeted from roughly 55,000 in January to barely 5,000 today. In the U.S., by contrast, 31% of the population has received at least one shot and 18% are fully vaccinated.

“Britain is the best argument for a delayed second dose strategy,” Emanuel said. “They seem to have done it pretty successfully. Even with the B.117 variant …. their numbers are pretty remarkable.”

The vast majority of U.S. vaccinations to date have used two-dose vaccines, despite the February authorization of Johnson & Johnson’s single-dose immunization.

Last month, Canada, too, mandated a four-month gap between first and second doses of the Pfizer-BioNTech and Moderna vaccines, a move that has led to anger and frustration especially from the country’s seniors. Preliminary research, which has not yet been peer-reviewed, has shown the approach may be less effective for older people, whose immune response to the vaccines is typically weaker than in younger people.

Members of Congress who have advocated for the change include two Democratic senators, Chris Van Hollen (Md.) and Martin Heinrich (N.M), as well as a number of staunchly conservative Republican physicians, like Sen. Roger Marshall (Kan.) and Rep. Andy Harris (Md.).

“As a threat rises from new disease variants, we write to request your consideration of a new strategy to maximize the population receiving the COVID-19 vaccine in the near term,” Van Hollen and Heinrich wrote last month in a letter to Jeff Zients, the White House pandemic coordinator. “We encourage you to explore deploying existing second doses as first doses and rely on growing real-time inventory to cover future follow-on booster shots.”

In a separate letter, Republicans lawmakers urged the Biden administration to issue a new emergency authorization allowing health officials to give only a single dose of vaccines developed by Moderna and a Pfizer-BioNTech partnership “until all vulnerable and essential populations are inoculated, and more vaccine doses become available.”

Their calls, however, largely fell on deaf ears, particularly in February and early March, when U.S. case rates were sharply down from their peak of roughly 250,000 in January.

The shift would likely require a nod of approval from the Food and Drug Administration, which warned against deviating from the three- and four-week intervals in January, prior to Biden’s inauguration. In a statement, the agency’s former commissioner, Stephen Hahn, said he found proposals for delayed dosing strategies “concerning,” and that the agency continues to “strongly recommend that health care providers follow the FDA-authorized dosing schedule.”

Tony Fauci, the country’s chief infectious diseases researcher, has argued that there isn’t solid evidence to back a delayed-dose strategy. Even if an initial first dose gives good protection against Covid-19, he said at a recent White House briefing, it’s unclear how long that protection would last.

Beyond posing an unnecessary risk to individuals’ immunity, Fauci has also warned that pivoting midway through the vaccine rollout could send the message that there’s no need to return for a second shot, whether it’s three or 12 weeks after their first.

Fauci has also warned that delaying second doses could help foster the growth of “escape” variants, or strains of the SARS-CoV-2 virus that are more likely to evade existing vaccines’ protectiveness.

A paper published this week in Nature, however, argued the opposite: There is little evidence that so-called “dose-sparing” strategies help to select for escape variants. The math, its authors note, is simple.

“[If] individuals who receive half as much vaccine (one versus two doses, or half the quantity of antigen per dose) achieve more than half the protection from clinical infection of those given a full regimen, then spreading the vaccine among more individuals will produce greater reductions in the number of clinical infections,” they wrote.

https://www.statnews.com/2021/04/02/democrats-and-republicans-alike-pressure-biden-administration-to-pursue-single-dose-vaccine-strategy/

Thank private risk-taking, not public funding, for Covid-19 vaccines, therapies

 A growing chorus of lawmakers and activists is calling on the Biden administration to invalidate patent protections for Covid-19 vaccines. As they see it, the federal government invested in the research that led to today’s vaccines so the private companies behind them shouldn’t benefit from intellectual property protections.

That argument is as misinformed as it is dangerous.

I’ll use the Moderna vaccine as an example. Though the National Institutes of Health and academics helped lay a scientific foundation for our understanding of messenger RNA — the relevant technology at the heart of Moderna’s shot — the vaccine itself is the result of years of privately backed research and development. That life-saving work wouldn’t have been possible without a predictable system of intellectual property protection.

It’s easy to come away with the misimpression that the recent crop of Covid-19 vaccines is mainly the product of an aggressive federally backed research effort. Operation Warp Speed, after all, was an $18 billion initiative aimed at fostering vaccine production. There’s no doubt it helped accelerate the testing and manufacturing of successful vaccines.

But the technologies behind the leading Covid-19 vaccines long predate Operation Warp Speed. They are, in fact, the product of extraordinary private sector investment.

Moderna, for example, had been working on its mRNA technology for a decade before Covid-19 emerged as a global health threat. During that period, investors risked tens of millions, year after year, in the hopes that a breakthrough method for generating stem cells from messenger RNA might be used to create a host of powerful new treatments.

This gamble ultimately paid off. The years of work on mRNA enabled Moderna to design a successful Covid-19 vaccine just 42 days after the virus was genetically sequenced.

But there was no guarantee, federal or otherwise, that Moderna’s new technology would be a success. What made investors willing to risk so much money was a system of intellectual property protection that would allow them, if successful, to recoup and profit from their investment.

Without such protection, biotech firms would have no way of preventing copycats from stealing their technology, undercutting them on price, and removing any chance for innovator firms to earn back their upfront costs. In such a no-holds-barred environment, there would be little reason to invest in medical technology at all, and breakthroughs like Moderna’s vaccine would be all but impossible. This is precisely the scenario that anti-patent crusaders risk creating.

The same can be said of those pushing for government price controls. By removing the ability of private investors to profit from successful medical advances, such policies would destroy the incentive structure that enabled Moderna and other firms to deliver vaccines at record speed.

Some misleadingly claim that a government takeover of the fruits of U.S. medical innovation is justified because the government funds basic research through the National Institutes for Health. But federally supported basic research is more akin to public infrastructure spending than to private-sector research and development efforts.

When the government invests in roads and bridges, it creates the conditions for increased economic activity, employment, and other positive outcomes — including higher tax revenue for government. It would be absurd for the government to claim ownership of a company because trucks transport its products on publicly-funded roads and bridges.

The same is true of the basic research funded by the NIH. The federal government invests in the scientific community’s understanding of cancer or heart disease or Covid-19. But it relies on the private sector to do the risky and expensive work of turning promising discoveries into practical medical treatments.

For real-world context of this dynamic, look at remdesivir, an antiviral drug, which was the first drug approved by the FDA to treat Covid-19. It is the culmination of a nearly $1.8 billion effort on the part of Gilead Sciences. Over the course of 20 years, the company synthesized, patented, and manufactured the compound to treat a range of coronaviruses.

Questions have been raised about the government’s role in the drug’s discovery and its entitlement to patent rights. But the truth is, federal agencies centered their efforts on standard testing of the drug’s existing antiviral properties. Their work did not involve modifications to remdesivir or its parent compounds, according to a new report from the Government Accountability Office. And, all told, federal contributions amounted to $162 million, which pales in comparison to Gilead’s investment.

That critical — but often misunderstood — division of labor is reflected in the research budgets of private-sector drug firms writ large. In 2019, America’s largest pharmaceutical firms spent $83 billion on R&D. That number is more than double the entire NIH budget for that year — and doesn’t include the billions spent by small startups at the forefront of innovation.

The Covid-19 vaccines and therapies that are helping to end this pandemic are proof of the enormous power of private drug innovation. Whether they realize it or not, those calling for patent waivers and price controls are jeopardizing the system that made these vaccines possible.

John Stanford is executive director of Incubate, a Washington-based coalition of life-science venture capitalists.

https://www.statnews.com/2021/04/05/thank-private-risk-taking-not-public-funding-for-covid-19-vaccines-therapies/

Chembio Diagnostics launches rapid COVID-19 test

 Shares of Chembio Diagnostics Inc. CEMI, +57.88% skyrocketed 63.8% on record volume in afternoon trading Monday, to pace all gainers listed on major U.S. exchanges, in the wake of the point-of-care diagnostics company's announcement of the commercial launch of its rapid COVID-19/flu test. The stock was on track for the biggest one-day percentage gain since it doubled, on March 12, 2004. Trading volume ballooned to 206.6 million shares, compared with the full-day average of less than 1 million shares. The company said its test has been granted emergency use authorization by the Food and Drug Administration. Chembio said after Thursday's closing bell that the product, which produces results in 15 minutes, requires no instrumentation and simultaneously differentiates SARS-CoV-2 antigens and influenza Type A and Type B infections, is immediately available for shipment. "As COVID-19 converges with the flu, it is critical for physicians to be able to quickly differentiate between these viruses at the point-of-care, which present with nearly identical symptoms, in order to take appropriate clinical actions and maximize efficient use of healthcare resources," said Charles Caso, vice president of sales and marketing at Chembio. The stock has run up 21.4% year to date, while the S&P 500 SPX, +1.40% has gained 8.6%.

https://www.marketwatch.com/story/chembio-diagnostics-stock-rockets-on-record-volume-after-commercial-launch-of-rapid-covid-19-test-2021-04-05

Invitae: $1.15B Investment to Support Ongoing Growth Initiatives

 Invitae (NYSE: NVTA), a leading medical genetics company, today announced that a small group of investors, led by SB Management, a subsidiary of Softbank Group Corp., will make an investment of $1.15 billion in convertible senior notes to support the Company's future growth initiatives.

"Invitae's mission is to deliver genetic information to improve healthcare for billions of people at all stages of life. With the support of our long-term shareholders, we're creating the platform to support the routine use of genetics in mainstream medicine to result in better healthcare for everyone," said Sean George, co-founder and chief executive officer of Invitae. "This investment will help us continue to fuel our growth, including expanding our platform, services and menu through both in-house development and the addition of complementary companies and technologies as we work to build a differentiated platform uniquely capable of driving the transition to personalized medicine."

"Invitae has a definitive head start in the rapidly expanding market for clinical genetic sequencing. Their comprehensive diagnostic products are well positioned to further grow the global understanding of how genomics predispose populations for certain diseases. These datasets will inform treatment and dramatically improve patient outcomes," said Akshay Naheta, chief executive officer of SB Management, a subsidiary of SoftBank Group Corp. 

Under the terms of the investment, the participating investors, including SB Management, will purchase a total aggregate principal amount of $1.15 billion in Convertible Senior Notes due 2028 (the "Notes"). The Notes will have an initial conversion price of $43.18 per share of the Company's common stock, subject to customary anti-dilution and other adjustments. The initial conversion price of $43.18 represents a 20% premium to the Company's average 5-day trailing volume-weighted average price as of April 1, 2021. The Notes will mature on April 1, 2028, unless earlier converted, redeemed or repurchased. The Notes will bear 1.5% interest per year. Upon conversion, the Company will have the right to elect settlement in cash, shares, or any combination thereof in its sole discretion.

https://www.biospace.com/article/releases/invitae-announces-1-15-billion-investment-supporting-ongoing-growth-initiatives/

Takeda, CSL to end alliance as plasma-based COVID-19 drug fails key test

 

• An experimental, concentrated antibody solution from Takeda and CSL Behring failed to reduce the risk of disease progression in hospitalized COVID-19 patients in a large study funded by the U.S. government.
• The medicine was developed by Takeda and CSL through an alliance that included several other drug manufacturers and a clinical trial network set up for drugs to test HIV. On Friday, Takeda reported the so-called hyperimmune globulin treatment, when added to standard care including Gilead's Veklury, didn't meet any of the study's efficacy goals.
• The companies will now end their partnership, which was called the CoVIg-19 Plasma Alliance and formed last April to quickly test the blood-based treatment. The agreement, however, could provide a "framework for future collaborative opportunities," Takeda said.

In the early days of the coronavirus pandemic, drugmakers, governments and regulators partnered in creative and unusual ways to quickly respond to the global health threat.

The National Institutes of Health, for instance, teamed with a big group of drugmakers to form what's known in shorthand as "ACTIV" and has been testing a variety of different potential treatments and vaccines for COVID-19. Sanofi and GlaxoSmithKline, two rival vaccine developers, teamed up to make a coronavirus shot. Other philanthropies, biotechs and venture firms joined forces with ambitions to conduct targeted and speedy research.

Taked and CSL were among them. Both have considerable experience with plasma-derived therapies, with approved products for hepatitis, certain immune deficiencies and other diseases. And both decided to forego their own drugs and work together on a treatment for coronavirus infections, claiming that with a group of manufacturers — Biotest, BioPharma Plasma, GC Pharma, LFB, National Bioproducts Institute, Octopharma and Sanquin — they could accelerate the development of a treatment and, if successful, widely supply it.

The alliance was formed at a different stage of the pandemic. Coronavirus vaccines from Moderna, Pfizer and others were just beginning clinical testing, and much of the focus was on testing and advancing repurposed or existing drugs.

One that received plenty of attention, for instance, was convalescent plasma, which is an antibody-rich blood sample from a recovered COVID-19 patient. The approach has been used for a century to treat certain infectious diseases and respiratory infections, and was thought of as a potential COVID-19 therapy as well.

Takeda and CSL aimed to take the idea a step further. Because convalescent plasma is taken from individuals, its therapeutic punch can be highly variable and depend on the levels of antibodies in each sample. Takeda and CSL extracted antibodies from a much wider pool of donated plasma, hoping to develop a more concentrated and standardized medicine — hyperimmune globulin — that could provide a reliable benefit. If potent, it could have served as an alternative to the synthetic antibody drugs developed by Regeneron, Eli Lilly and others.

Yet both strategies for plasma-derived therapies didn't pan out as hoped. The Food and Drug Administration controversially granted emergency clearance to convalescent plasma last year based on results from an expanded access program from the Mayo Clinic. But the decision, which reportedly came amid political pressure from the Trump administration and opposition from the National Institutes of Health, hurt the credibility of the agency. The FDA later narrowed its authorization as multiple controlled trials have since found limited benefit to treatment, if any.

Takeda and CSL's drug fell short in a study of roughly 600 patients hospitalized with COVID-19 and at high risk of serious complications from the disease. The companies didn't provide specifics, but treatment didn't succeed on any of the efficacy measures, like a positive change on a 7-point scale that evaluates the condition of COVID-19 patients. Results will be published in a peer-reviewed journal.

The companies will end their partnership, but said the experience could provide a model for similar, future collaborations should another public health crisis arise.

https://www.biopharmadive.com/news/takeda-csl-behring-covid-plasma-alliance-results/597781/