Covid-19 roundup: Carl June on having Covid-19 and his plan to treat it; NIH preaches caution; 2 new vaccines enter clinic
Carl June had Covid-19. Now he’s trying to figure out how the world can treat it.
In an interview with the Philadelphia Inquirer, the CAR-T pioneer and University of Pennsylvania immunologist revealed that he had been sick with a “mild to moderate” case of the virus for 3 weeks. Now recovered, he is trying to donate his plasma and he has some thoughts about how the biomedical community should pursue new treatments.
Promising experimental treatments exist, he said, but they are being pursued in an inefficient manner, with hundreds of different trials for therapies ranging from holistic remedies to experimental antivirals to repurposed approved drugs. Many of those trials are testing the same treatments.
“There are many redundant trials, not prioritized based on science but on companies’ portfolios,” June told the Inquirer. “They use patients up. It doesn’t allocate basic resources wisely.”
For example, he named the more than a dozen trials being run on Actemra, the Roche drug that blocks the immune signal IL-6. June originally used the drug in 2013 to successfully treat the overactive immune response — called cytokine storms — that emerged as a complication of his CAR-T cancer treatment. Doctors believe cytokine storms, prompted by the virus but remaining even after the virus is largely gone, are causing some of the life-threatening symptoms seen in some Covid-19 patients.
June said he was confident Actemra would be effective, but said it was too expensive to be the panacea for a global pandemic. “They can’t afford it in India,” he said. “They need something cheap.”
So June is trying to organize a trial for a different immune-suppressing drug: cyclosporine. The compound, used to prevent rejection in organ transplant patients, is a generic and already exists in large supply, making it an ideal candidate for the developing world. In a trial, it would be given to patients when they are first hospitalized to see if it prevents an immune overreaction. The Penn ethics review board is currently reviewing the trial.
Both drugs, though, have the potential to backfire, turning down the immune system’s ability to fight the virus itself. Roche said today they expect results on Actemra in June. — Jason Mast
Oxford’s Covid-19 vaccine program to enter PhI tomorrow
Another Covid-19 vaccine will enter the clinic tomorrow.
A group at Oxford University led by immunologist Sarah Gilbert and backed by the UK government will begin testing their vaccine candidate in health volunteers, with the hope of experimentally vaccinating 500 people by the middle of May. The vaccine, made of recombinant DNA and delivered through an adenovirus, has been in development since shortly after the sequence of the novel coronavirus became available in early January.
The UK government has made £20 million (roughly $25 million) available to back the effort, Secretary of State for Health & Social Care Matt Hancock announced this week. They also made £22.5 million available for an RNA vaccine project at the Imperial College of London.
Gilbert, who has previously worked on vaccines for outbreaks such as SARS and Zika, has laid out an an aggressive timeline for the vaccine, telling The Lancet last week that in a best-case scenario she hoped to have both Phase III efficacy data on 5,000 volunteers and the ability to manufacture large doses by the fall, with the caveat that “these best-case timeframes are highly ambitious and subject to change.”
The fall is also when Moderna — which built the first vaccine to enter clinical trials — has said they could have a vaccine ready for emergency use, although the company has said it’s unclear if those would be given as part of a trial, under compassionate use, or a different protocol.
J&J, which has a $1 billion partnership with BARDA, and CanSino, the leading Chinese Covid-19 vaccine program, also use adenovirus-based vaccines. — Jason Mast
NIH guidelines preach caution, patience on treatments
The NIH has posted its official treatment guide for Covid-19, and the major takeaway is a message many scientists have been preaching: Wait for more evidence before leaning one way or another. Developed by a panel of experts, many of whom are frontline clinicians, the “living document” covers two widely-discussed categories of therapies: antivirals, which target the virus, and host modifiers and immune-based therapies, which may target the patient.
In the antiviral realm, the panel concluded that there are insufficient clinical data to recommend either for or against the three hottest drugs: the antimalarial drugs chloroquine and hydroxychloroquine, or Gilead’s repurposed Ebola drug remdesivir.
The guidelines stand in sharp contrast with President Trump’s enthusiastic endorsement of hydroxychloroquine and chloroquine. Every turn of events surrounding the pair of drugs — which are also taken by patients with autoimmune diseases such as lupus and rheumatoid arthritis — have elicited strong opinions, from the FDA’s controversial emergency use authorization to the results from the small studies conducted thus far.
Outside of a clinical trial, the NIH experts suggest physicians don’t prescribe hydroxychloroquine plus azithromycin for fear of toxicity. The same advice applies to HIV protease inhibitors such as lopinavir/ritonavir “because of unfavorable pharmacodynamics and negative clinical trial data.”
Immune-based therapies didn’t offer clearer answers. The panel similarly concluded it’s too early to say either yay or nay on convalescent plasma, hyperimmune immunoglobulin, IL-6 inhibitors or IL-1 inhibitors. As for interferons and JAK inhibitors — a class that encompasses Eli Lilly’s Olumiant, now being tested in patients — they’re not recommended unless in a trial setting. — Amber Tong
Roche’s Severin Schwan lambasts antibody test ‘disaster’
Roche’s mild mannered CEO has some harsh words reserved for the developers behind some of the antibody tests currently on the market. “It’s a disaster,” Schwan was cited as saying on a conference call.
Having gotten the green light early to deploy its coronavirus tests, the Swiss pharma giant is planning to release an antibody test in May. By analyzing people’s blood and detecting any antibodies against SARS-CoV-2, the diagnostic is supposed to tell whether they have ever been infected.
A number of such tests, also known as serological tests, have already been rolled out to the market. They come from about 90 companies, many based in China, and were authorized before getting reviewed. Multiple news outlets have reported that experts are concerned about their accuracy, questioning whether the FDA — chided for its slow response to the nasal swab tests — set the quality standards too low this time around in pursuit of speed.
“These tests are not worth anything, or have very little use,” Schwan said, according to Reuters. “Some of these companies, I tell you, this is ethically very questionable to get out with this stuff.” — Amber Tong
BioNTech, Pfizer moves into human trial with mRNA vaccine candidate in Germany
BioNTech and Pfizer have secured approval from German authorities to begin testing its four vaccine candidates in humans. The Phase I/II trial will enroll 200 healthy volunteers to find the optimal dose.
Here’s an overview of the BNT162 program:
Two of the four vaccine candidates include a nucleoside modified mRNA (modRNA), one includes a uridine containing mRNA (uRNA), and the fourth vaccine candidate utilizes self-amplifying mRNA (saRNA). Each mRNA format is combined with a lipid nanoparticle (LNP) formulation. The larger spike sequence is included in two of the vaccine candidates, and the smaller optimized receptor binding domain (RBD) from the spike protein is included in the other two candidates. The RBD-based candidates contain the piece of the spike that is thought to be most important for eliciting antibodies that can inactivate the virus.
The partners are also awaiting regulatory decisions in the US, while BioNTech is working with Fosun to begin trials in China. — Amber Tong
San Diego biotech tests interstitial lung disease drug for severe Covid-19 patients
As the severity and danger of respiratory complications among Covid-19 patients become clear, aTyr is joining the long line of biopharma companies pitching their anti-inflammatory drugs to the fight. The San Diego-based biotech has recently come up with positive safety data in a Phase Ib/IIa study involving patients with pulmonary sarcoidosis and will now launch a Phase II study in severe Covid-19 patients.
The theory is that ATYR1923 downregulates T-cell responses, thereby dampening the inflammatory cytokine and chemokine signaling. The drug can also improve lung function, aTyr added, based on animal models.
The trial will enroll 30 patients in the US, with 10 patients each randomized to take 1mg/kg, 3mg/kg or placebo. — Amber Tong
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