Covid-19 roundup: FDA commissioners call for more ‘concerted effort’ on convalescent plasma R&D; Regeneron boosts case for antibody cocktail with new animal data
Four former FDA commissioners have coalesced around a century-old treatment they believe can give the best weapon against Covid-19: Convalescent plasma.
Writing in The Washington Post, former FDA commissioners Mark McClellan, Margaret Hamburg, Robert Califf and Scott Gottlieb said that while more work needs to be done to prove it’s safe and effective, convalescent plasma was a “promising treatment” that “could help millions of patients with the novel coronavirus both here and abroad.” They warned, though, that for it to become an effective tool in the US’ Covid-19 response, a more “concerted effort” is needed to recruit donors and run trials.
“But if this is going to work, we need to do it right,“ they wrote.
The former FDA commissioners are hardly the first to call for a focus on plasma. The approach has been used to combat viral and bacterial outbreaks since before the Spanish flu and Chinese researchers turned to it to treat coronavirus patients as early as January. In March, amid efforts by researchers at Johns Hopkins, the FDA gave emergency clearance both to start convalescent plasma trials and to give out the therapy under emergency use. President Trump promoted the therapy at the American Red Cross last week. It involves taking antibody-rich serum from the blood of patients who have recovered from Covid-19 and transferring it to newly infected patients to boost their immune response.
The ex-commissioners, though, called for those efforts to be more directed. So far, over 40,000 Americans have received plasma through a joint program between HHS and the Mayo Clinic, yet there still has yet to be a large randomized trial to determine if the therapy works and on which patients. The former commissioners compared the current situation to the one doctors faced in the spring with hydroxychloroquine, where there was a theory for why it should work but little data.
“Thousands of covid-19 patients have been treated with plasma, but we are not much closer to definitively answering those questions,” they wrote.
The commissioners noted, though, that efforts were underway. They touted the work of The Fight Is In Us, coalition that is encouraging more people to donate their plasma.
Some of those efforts are already underway. The NIH is about to start trials testing plasma, along with monoclonal antibodies. And Johns Hopkins received $35 million last week from the DoD for nationwide clinical trials. The commissioners noted, though, that only a small fraction of Covid-19 patients can enter those trials. They called for larger, coordinated studies, citing as an example the UK Recovery studies that showed hydroxychloroquine didn’t work and the steroid dexamethasone did.
“We can’t waste precious time and put people at risk by treating them with therapies that don’t work or miss opportunities to collect data and determine when a treatment is beneficial,” they wrote. — Jason Mast
Regeneron posts animal data, raising hopes for antibodies as both prophylactic and treatment
New data from animal studies of Regeneron’s antibody cocktail suggest it can both prevent and treat Covid-19, boosting the company’s case as it moves through Phase II/III programs.
The findings in rhesus macaques and hamsters — which have not been peer reviewed — also echo predictions by ex-FDA commissioner Scott Gottlieb and Luciana Borio, the former director of medical and biodefense preparedness at the National Security Council, that antibodies will be the bridge to a vaccine.
Not only did the antibodies lower viral load in the animals, they also reduced virus induced pathology. Regeneron scientists aren’t shy about stressing the significance here.
“The ability of REGN-COV2 to almost completely block detection of subgenomic species of SARS-COV-2 RNA matches or exceeds the effects recently shown in vaccine efficacy studies using the same animal models,” the team, led by Christos Kyratsous, wrote. “Additionally, the observed accelerated reduction of upper airway virus load in rhesus macaques treated with REGN-COV2 contrasts the lack of impact on viral load in remdesivir treated animals, where reduced viral load could only be observed in lower airways with no differences in nasal viral RNA levels.”
In the study, rhesus macaques served as a model for transient and mild disease while the golden hamster typically manifests a much more severe form accompanied by rapid weight loss and severe lung injury, the researchers wrote. For the prophylactic setting, they tested two doses (50 mg/kg and 0.3 mg/kg) and exposed the animals to the virus 3 days after antibody administration.
When armed with the antibodies, which bind to different epitopes on the coronavirus spike protein, the animals were able to withstand even a higher viral challenge.
Compared to placebo, REGN-COV2 also helped animals clear the virus faster when given one day post-infection. Then there’s the clean safety profile, with no evidence of antibody-mediated enhancement of disease.
All of this points to the potential of clinical benefit, and Regeneron doesn’t have to wait long to confirm it. A trial involving non-hospitalized patients is slated for completion in November and the study for hospitalized patients will wrap next January, but the first cut of data could always emerge earlier.
In an ideal scenario, the data will support an emergency use authorization, at which point Regeneron will have tens to hundreds of thousands of doses lined up. Having nabbed the first therapeutic contract from Operation Warp Speed totaling $450 million, the biotech has been ramping up its manufacturing to deliver an estimated 70,000 to 300,000 treatment doses and around 420,000 to 1.3 million prevention doses as early as late summer. — Amber Tong
DoD shines a spotlight on GM-CSF, offering $35M to bankroll PhII studies
GM-CSF, or granulocyte macrophage-colony stimulating factor, is emerging as the next target for drug repurposing after a slate of IL-6 therapies sputtered out.
Lexington, MA-based Partner Therapeutics has secured a $35 million contract with the US Department of Defense to test its inhaled recombinant GM-CSF, Leukine, for Covid-19 patients who experience acute hypoxemia.
The biotech plans to launch the first of two Phase studies in August 2020, evaluating the drug in treating Covid-19 associated acute hypoxemic respiratory failure, with oxygenation and percent of patients intubated as the key metrics. The funding will also support regulatory filings and expansion of production capacity.
These new data will supplement results from more than 60 patients who have been enrolled in a trial PTx is conducting in Belgium.
“GM-CSF is essential for lung health. Emerging data suggest that COVID-19 is associated with immune dysfunction including deficiency of alveolar macrophages and GM-CSF,” said Debasish Roychowdhury, chief medical officer at PTx. “Treatment with Leukine may confer benefit to patients with acute respiratory distress and potentially reduce long term complications.”
GlaxoSmithKline brought some attention to the target when the pharma giant announced in May that it would test its rheumatoid arthritis drug otilimab for Covid-19, with a goal to block a key cytokine and ease the effect of an infection on the lungs. The NIH lent more credence to the concept recently by adding Humanigen’s lenzilumab to a master protocol comparing a combo with remdesivir to remdesivir alone. — Amber Tong
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