Covid-19 roundup: AstraZeneca, Pfizer come under fire for production delays; Moderna considers third booster dose to squash new variants
The vaccine race is shaping up to be much more than just a sprint toward authorization.
A day after Merck dropped out entirely, controversies are simmering around AstraZeneca and Pfizer/BioNTech, J&J says it will come along soon, while Moderna is refueling for the long haul.
With vaccine rollout still in bottlenecks even across wealthy nations that have essentially bought up initial supplies, the emergence of new variants is complicating long-term planning. For latecomers, who must now make critical decisions about their still-experimental programs, questions remain on just what levels of efficacy are good enough — and for whom.
“We continue to progress our COVID-19 vaccine candidate and look forward to sharing details from our Phase 3 study soon,” J&J CEO Alex Gorsky said in an announcement of quarterly results, just before he told CNBC they expect those results next week.
— Carl Quintanilla (@carlquintanilla) January 26, 2021
EU blasts AstraZeneca for vaccine production delays, threatens export control
AstraZeneca may still be days away from winning an anticipated OK for its vaccine in the EU, but the troubles and controversy are already pouring in.
The pharma giant was swarmed by backlash on Monday after it informed the European bloc that production lags mean it would not be able to deliver the promised number of doses laid out in a supply contract. That followed reports in German media claiming that the vaccine, developed on adenovirus technologies out of Oxford University, had an extremely low efficacy in those over 65 — which AstraZeneca denied.
So far, the AZD1222 jab has only been approved in the UK. But the EMA is reportedly set to make a decision this week.
In a meeting with AstraZeneca, EU officials all but accused the company of prioritizing other nations at the expense of their member countries, Politico reported. They subsequently called for tighter controls on coronavirus vaccine exports.
Stella Kyriakides, the European Commissioner for Health and Food Safety, aired her dissatisfaction publicly:
Discussions with @AstraZeneca today resulted in dissatisfaction with the lack of clarity and insufficient explanations. EU Member States are united: vaccine developers have societal and contractual responsibilities they need to uphold.
— Stella Kyriakides (@SKyriakidesEU) January 25, 2021
Behind the scenes, one EU diplomat described to Politico two reasons given by AstraZeneca for the production shortfall at a Belgium plant: materials sourcing and manufacturing. But with a dearth of evidence to support those explanations, they also noted that the company had already shipped doses made in that facility to other customers around the world.
The EU had cut a deal to pre-order 300 million doses at an undisclosed price, with an option to add 100 million.
“Trust has been severely shaken,” a Commission official said, adding: “To this day, it has not been fully explained what happened to the money and what has the company done on its obligation to manufacture at risk.” — Amber Tong
Moderna considers third booster dose to squash new variants
Moderna is testing booster options to be sure its Covid-19 vaccine can stamp out emerging variants — which could mean a third shot for some participants.
The biotech has been following a range of variants, at least five of which involve multiple mutations, president Stephen Hoge said during an investor call Monday afternoon. The three gaining the most attention are: B.1.1.7, first detected in the UK; B.1.351, identified in South Africa; and P.1, found in Brazil and Japan.
The UK variant has 17 genetic mutations in the viral genome, with eight located on the spike protein. The South Africa variant has 10 mutations to the spike protein. And all three strains have developed multiple mutations at the top of the spike protein, near the receptor binding domain and the N-terminal domain (NTD).
“These are a particular concern, because when we develop antibodies that neutralize and protect against the coronavirus, we really find that the antibodies that bind at the top of the spike protein are particularly effective,” Hoge said.
To see if their vaccine, mRNA-1273, offers protection against the new strains, Moderna conducted in vivo studies using sera from eight Phase I participants who received two 100 µg doses, and from primates given either two 30 µg or 100 µg doses.
The results? The vaccine worked well enough, appearing to be “fully effective” against all strains tested, according to Hoge. The not-so-good news is that there was a six-fold reduction in neutralizing antibody titers against the South Africa variant. While the levels are still believed to be high enough to be protective, they may lead to earlier waning of immunity, according to Moderna.
Moderna is testing boosters “out of an abundance of caution,” CEO Stéphane Bancel said during the call. One option is a third dose of mRNA -1273. But the biotech is also testing a new strain-specific booster, dubbed mRNA-1273.351, in preclinical studies and a Phase I trial in the US.
CMO Tal Zaks said he expects the original regimen will be protective in the near term, even against the South Africa variation. A third booster shot likely wouldn’t be necessary until six to 12 months after the primary series is given, he said.
In addition, Moderna says its booster shot (both mRNA-1273 and mRNA-1273.351) could potentially boost immune response “in combination with all of the leading vaccine candidates.”
“As we published in the past, our vaccine is very good at developing and boosting those titers,” Hoge said during the call. “And we believe an mRNA vaccine, or potentially a third dose of an mRNA vaccine, is a way that if it becomes necessary in the future, we can raise those titers again. And that’s particularly important as we think about, over time, waning or decreasing immunity, specifically to some of these new emerging strains.” — Nicole DeFeudis
Italy and Sweden call Pfizer out for vaccine distribution troubles
As Pfizer’s vaccine deliveries run behind schedule in the EU and questions linger about how much to charge for each vial, two dissatisfied countries are standing up to the big pharma.
Italy is once again threatening legal action over shipment delays that are affecting the country’s vaccine rollout, Reuters reported. On Monday, the government sent a formal letter of notice to Pfizer, urging them to comply with contractual commitments for vaccine delivery.
Last week, the Wall Street Journal reported that Pfizer’s shipment was cut by 29%. Pfizer and BioNTech had warned the EU and Canada earlier this month to expect fewer doses as they upgrade their Belgium factory. But Italy has said it doesn’t appreciate the short notice.
Pfizer could be accused of breaching its contract with the EU if it doesn’t meet contractual obligations for vaccine delivery, Reuters reported. And Prime Minister Giuseppe Conte said the country is prepared to use all available legal tools, according to the news agency.
Sweden is withholding its payments to Pfizer, after the last billing statement raised some eyebrows. Pfizer charged the country for six doses per vial, instead of five like it initially agreed, Reuters reported.
Earlier this month, the EU found that it was possible to squeeze out a sixth dose because of overfilling. But there’s a catch: Without a special syringe, those administering the vaccine can’t quite get that sixth dose out. Now Sweden is calling on the EU Commission and Pfizer to agree on how many doses can really be extracted.
“This is unacceptable. If a country only has the ability to extract five doses, it has received fewer doses for the same price,” Sweden’s vaccine coordinator Richard Bergstrom told the daily newspaper Dagens Nyheter, per Reuters.
Until the issue is resolved, Sweden’s health agency is holding onto its payments — and the receipts. — Nicole DeFeudis
Shionogi outlicenses DP1 treatment to BioAge in US and Europe
Japanese drugmaker Shionogi has sold rights to a Covid-19 treatment to BioAge Labs, a biotech in California.
The experimental drug, dubbed BGE-175, was originally developed to treat allergic rhinitis by inhibiting the DP1 receptor, and it has been tested in over 2,400 patients thus far, Shionogi said Tuesday. But its apparent ability to enhance immune function suggests it could prove useful in Covid-19 as well.
A study at the University of Iowa also indicated that an existing DP1 antagonist proved effective in treating the coronavirus responsible for the 2003 SARS epidemic in a mouse model. The pair became aware of the target after an AI analysis conducted by BioAge indicated its potential, Shionogi said.
With the deal, Shionogi will receive an undisclosed upfront payment as well as potential milestones and royalties. BioAge, meanwhile, will be able to market any finished Covid-19 product in the US and Europe and obtain exclusive bargaining rights to expand the deal into additional indications.
BioAge is expected to launch Phase II trials in Covid-19 within the first half of 2021.
Shionogi is also developing a recombinant protein vaccine for Covid-19 that is now in combined Phase I and II trials in Japan. — Max Gelman
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