The search for effective COVID-19 drugs presses on, with the National Institutes of Health (NIH) launching a new trial of three immune modulator drugs in hospitalized patients.
The phase 3 study will examine Johnson & Johnson’s popular TNF blocker Remicade, Bristol Myers Squibb’s arthritis med Orencia and an experimental drug from AbbVie called ceniciviroc, the NIH said Friday. The goal is to see whether these therapies can be repurposed to control potentially life-threatening immune overreactions in moderate to severe COVID-19 patients.
The NIH intends to enroll about 2,100 patients, all of whom will also get Gilead Sciences’ remdesivir, which the NIH considers as the current standard of care.
The new trial, dubbed ACTIV-1 IM, builds on previous findings from another NIH-run study that showed remdesivir could cut patients’ recovery time by 30%, with benefits most pronounced in severe patients that require some oxygen support but not those on invasive ventilation. But still, consensus is that the med isn’t a magic bullet for the disease.
In COVID-19, a patient’s immune system might release too many immune molecules as it tries to fight off the infection, triggering a condition called “cytokine storm,” in which critical organs are also under attack. Previously, the NIH found that adding Eli Lilly’s rheumatoid arthritis med Olumiant to remdesivir helped patients recover one day faster, an improvement of 12.5%. Patients on the combo also enjoyed better chance at clinical improvement after 15 days of treatment.
This time, investigators want to find out if adding any of those three anti-inflammatory drugs to remdesivir can achieve better outcomes in disease severity, recovery speed, and perhaps most importantly, death rate.
The study is expected to last about six months and, possibly less if an interim analysis finds a clear sign of benefit for one or more of the drugs.
The three agents emerged from a pool of more than 130 drugs, which were originally chosen based on their relevance to COVID-19, strong evidence for anti-inflammatory power and availability for large-scale supplies, the NIH said.
Besides those therapies, convalescent plasma and corticosteroid dexamethasone will also be allowed in ACTIV-1 IM as the treating physician sees fit. The FDA granted an emergency use authorization to convalescent plasma—which contains useful anti-coronavirus antibodies—based on a controversial study that found the treatment led to a 35% improvement in survival. As for dexamethasone, a large-scale U.K. study by University of Oxford researchers found it cut the risk of death by 35% in critically ill COVID patients on ventilators.
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ACTIV-1 IM adopts a so-called adaptive master protocol, which allows for evaluation of multiple drugs at the same time. Drugs that don’t work will be eliminated as the trial moves forward, and new candidates can be added into the trial potentially on top of drugs that have shown strong efficacy.
Similar protocol is also being adopted in the I-SPY COVID trial, a collaboration between a group of more than 20 biopharma companies and Quantum Leap Healthcare. That trial uses remdesivir and dexamethasone as the backbone standard treatment. It’s also testing AbbVie’s cenicriviroc, a former Allergan drug that blocks two inflammatory signal-transferring proteins, CCR2 and CCR5, for potential treatment of nonalcoholic steatohepatitis. Amgen’s psoriasis med Otezla and Takeda’s hereditary angioedema therapy Firazyr are also included in that program.