Covid-19 roundup: AbbVie jumps into Covid-19 antibody hunt; AstraZeneca shoots for 2B doses of Oxford vaccine — with $750M from CEPI, Gavi
Another Big Pharma is entering the Covid-19 antibody hunt.
AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.
Although early in the outbreak, AbbVie contributed its HIV antiviral cocktail Kaletra to clinical trials, this is the drug company’s first foray into developing new treatments for the novel virus. Although the Illinois-based pharma has little apparent experience in developing antibodies for viruses, much of their commercial and research work centers on antibodies, including with the blockbuster TNF-blocking antibody Humira.
Last August, an NIH-funded clinical trial found two different antibody treatments to be the first and only effective treatments for Ebola, and when the new coronavirus emerged in December, researchers jumped in early to begin developing antibodies for it. Most prominently, Regeneron, which developed one of the effective Ebola treatments, and Vir, which owns the platform that helped develop the other one, announced programs in late January and early February.
AbCellera, a company known for helping Big Pharma and major biotechs develop their antibodies, then followed up with a program in partnership with Eli Lilly. Earlier this week, that program was the first to enter clinical trials, although Vir and Regeneron are each expected to start their own programs shortly. David Ho, the renowned HIV researcher and Columbia University professor, is working on his own antibody project, as are a long list of other researchers and small biotechs.
Neutralizing antibodies are a part of the body’s natural response to infection, as B cells create molecules that match receptors on the virus and, ideally, block its ability to enter cells while recruiting other immune cells to attack. That process though can take days or weeks, during which time the infection can spread. Over the last few decades, researchers have developed programs to create these antibodies artificially through transgenic mice or by extracting them from the blood of survivors. You can then give them to patients as a treatment or a preventative measure.
Creating a candidate antibody, though, is only step one, and the one that AbbVie has partnered on still has significant steps to take. The company holds an option to license for commercial and clinical development. — Jason Mast
AstraZeneca shoots for 2B doses of Oxford vaccine — with $750M from CEPI, Gavi
Forget 1 billion. AstraZeneca is now promising to supply 2 billion doses of Oxford University’s Covid-19 vaccine around the world per year.
Three new partners are coming on board to help reach that goal, as well as a broader vision to ensure access for nations that have been largely left out of the bargaining table.
CEPI — the coalition that’s been doling out grants to support other vaccine projects — is providing $383 million to support manufacturing of 300 million doses, while Gavi the Vaccine Alliance will chip in $367 million and be in charge of the procurement and distribution, a spokesperson told Wall Street Journal. A separate licensing agreement directs the Serum Institute of India to produce 1 billion doses for low- and middle-income countries, with the first 400 million due before the end of the year.
AstraZeneca CEO Pascal Soriot stressed in a statement that the vaccines will be provided “at no profit” during the pandemic.
The allocation of vaccines has become a top concern as governments scramble to secure first dibs for their citizens, triggering fears that people in poorer countries — populations who are most vulnerable to outbreaks — will be left out.
Oxford researchers also appear to be keeping that in mind as they organize the clinical trials, announcing today that Brazilian health authorities have cleared an application to include Brazil in the Phase III trial of the recombinant adenovirus vaccine candidate.
The university has begun recruiting 10,000 participants in the UK while AstraZeneca enrolls 30,000 in the US. For Brazil, the goal is to test the vaccine in 2,000 volunteers.
“Brazil is a priority for the study because of the ascendant curve of the COVID-19,” they wrote. — Amber Tong
CSL commits to funding, manufacturing Australian vaccine candidate
Australian pharma giant CSL is throwing its weight behind a Covid-19 vaccine developed at the University of Queensland, helping fund the development and signing up as the manufacturer.
UQ researchers are working with a “molecular clamp” enabled vaccine, whose core idea is to “lock” the unstable, prefusion version of the surface proteins on enveloped virus to generate synthetic proteins that can elicit a more efficient immune response. They have been experimenting with a couple of adjuvants, one from GSK and another provided by CSL subsidiary Seqirus.
Together with CEPI — which had backed the technology platform with a $10.6 million grant in early 2019, and later came back to fund a Covid-19 project — CSL will support the upcoming Phase I safety study as well as later-stage trials.
They will also prep their facilities in Melbourne for large-scale manufacturing. Should the vaccine be proven effective, they expect to scale the production to 100 million doses toward the end of 2021, while subcontracting out to other CMOs around the world.
“We’ll go as fast as we can, we’re emphasising it is a high-risk project,” CSO Andrew Cuthbertson told the Sydney Morning Herald. — Amber Tong
Lancet, NEJM retractions heighten scandal around papers tied to controversial data analytics firm
In the world of academic research, the coronavirus crisis has glorified the adage: Shoot first, ask questions later.
Scientists, desperate to separate the wheat from the chaff to hasten the search for a viable therapeutic, have been leaning heavily on preprint servers to vault their findings into the public sphere even before their peers have a chance to review their work. But now, the first big research casualty of the crisis has emerged from two prestigious medical journals.
It all started with a May 22 paper in the Lancet, which depicted the results of a large retrospective study on 96,000 Covid-19 patients, using hospital records procured by a little-known data analytics company Surgisphere. The conclusion — that coronavirus patients taking chloroquine or hydroxychloroquine were more likely to experience irregular heart rhythms and were more likely to die — eroded already waning scientific interest in the malaria therapies championed by President Donald Trump to such a degree that a number of key randomized, placebo-controlled trials testing them, including one by the WHO, ground to a halt.
Earlier this week, however, concerns about the retrospective study and other trials by the same lead author and Harvard professor Mandeep Mehra using Surgisphere data surfaced. After an open letter signed by 150 doctors called into question the paper’s conclusions and asked for public access to peer review commentary that preceded publication, on Tuesday Lancet editors acknowledged that “important scientific questions have been raised about data reported” and that an independent audit had been commissioned. On Wednesday, the WHO restarted its trial. Yesterday, the Lancet paper was retracted.
Surgisphere, the Chicago-based company founded by the fourth author of the Lancet paper Sapan Desai, refused to transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, citing confidentiality reasons. “As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process…based on this development, we can no longer vouch for the veracity of the primary data sources,” the first three authors of the Lancet study wrote in their retraction statement.
Meanwhile, another study led by Mehra using Surgisphere data in the New England Journal of Medicine (NEJM) was also retracted on Thursday.
Mehra connected with the vascular surgeon and science fiction writer Desai through a co-author, and personally reviewed the Surgisphere analyses for both the Lancet and NEJM papers, he told the news division of the journal Science.
But in the rush to publish during the Covid-19 crisis, he conceded he “did not do enough to ensure that the data source was appropriate for this use. For that, and for all the disruptions—both directly and indirectly—I am truly sorry.” — Natalie Grover
Reportedly snubbed by Operation Warp Speed, Novavax gets up to $60M in DoD funding
If reports by the New York Times and Bloomberg are on the money, then Novavax may not have made it to the whittled down shortlist for financial and logistical support from Operation Warp Speed — the White House-led ambitious public-private initiative to secure vaccine access for Americans before the end of this year.
As a consolation prize, however, the Covid-19 vaccine developer has been awarded a contract of up to $60 million by the US Department of Defense (DoD) to produce of several components of the vaccine in the country. The deal includes a 2020 delivery of 10 million doses of the vaccine — called NVX‑CoV2373 — for DoD that could be used in Phase 2/3 clinical trials or under an emergency use authorization (EUA) if granted by the FDA, the company said.
Novavax, which has a pipeline of experimental vaccines for RSV, influenza and Ebola, has not yet managed to score any FDA vaccine approvals akin to some other Covid-19 vaccine hopefuls such as Moderna and Inovio. To make its candidate, Novavax generated an antigen derived from the spike protein of SARS CoV 2, the virus that causes Covid-19, and added an adjuvant to enhance the immune response to the vaccine.
An early-stage study was kicked off last month, and preliminary data should be available by July. CEPI is putting in up to $388 million to fund the development.
Reportedly, Novavax was included in the initial 18-name shortlist for Operation Warp Speed.
Five groups — Moderna, J&J, the joint AstraZeneca-Oxford, the Pfizer, BioNTech partnership and Merck — who have made it to whittled down shortlist as reported by the NYT and Bloomberg. But vaccines made by Novavax, Sanofi, Inovio, Medicago, the U.S. Army, British American Tobacco, Codagenix, Institut Pasteur, Vaxart, NantKwest, Geovax, Greffex, and the University of Queensland, were on the initial 18-name shortlist, according to a Science report.
In mid-May however, the HHS put out a statement saying it had a list of 14 efforts — from the more than 100 candidates in development at companies and universities — as a starting point. The official word from the HHS on what groups the shorter shortlist contains is expected shortly.
“It’s typical Operation Warp Speed, where everything is sort of cryptic and it’s unclear what they’re actually saying,” said Peter Hotez, a vaccine researcher at the Baylor College of Medicine who is part of a team developing a COVID-19 vaccine in an interview with Science and serves on the vaccine committee of a public-private partnership organized by the NIH that is supposed to assist Operation Warp Speed run clinical trials of chosen vaccines.
But he and several other members of this committee told Science that Operation Warp Speed did not ask for their input in the selection. “We’re sort of like two parallel universes,” Hotez said. — Natalie Grover
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