Master protocols on deck as low enrollment stops Chinese trials of remdesivir
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With both placebo-controlled Chinese trials of remdesivir halted, master protocols are now the best bet to demonstrate efficacy, or lack thereof, for Gilead’s antiviral against SARS-CoV-2.
Gilead Sciences Inc. (NASDAQ:GILD) disclosed on Friday that a Phase III remdesivir trial run by the China-Japan Friendship Hospital in COVID-19 patients with severe disease ended early due to low enrollment. Now, a second Phase III Hubei trial, in patients with mild to moderate disease, is also suspended, according to ClinicalTrials.gov. Both trials on the site were updated Wednesday with the message: “The epidemic of COVID-19 has been controlled well in China, no eligible patients can be enrolled at present.”
In a March guest commentary in BioCentury, Zhi Hong wrote that having multiple small and inadequately controlled studies competing for the same patients and clinical resources could make it harder to enroll COVID-19 patients in trials and assess efficacy. Hong is president and CEO of Brii Biosciences Ltd. (see “Fewer is Better”).
At the time, Hong predicted that the pair of remdesivir trials in Hubei may be forced to stop without being completed as planned due to early trouble enrolling patients, and touted the adoption of “well-designed and flexible master protocols that can provide the needed collaborative framework to identify the right medicine for the right patients, or at-risk population, at the earliest time.”
At least six master protocols for therapeutics are under way for COVID-19; of those, trials run by NIH’s National Institute of Allergy and Infectious Disease (NIAID), the WHO, and the Institut National de la Sante et de la Recherche Medicale (INSERM) each are testing a remdesivir arm (see “Master Protocols Emerge as a Critical Clinical Tool”).
Data from NIAID’s adaptive master protocol trial are due in May, and a publication on the severe disease Hubei trial is expected soon. Both trials, as well as the Chinese trial in mild to moderate patients, are placebo-controlled; Gilead’s two remdesivir studies are not.
The company expects data from its own trials in severe and mild-to-moderate disease in late April and May, respectively.
Including remdesivir, at least 256 therapies and vaccines are in development for COVID-19, according to BioCentury’s COVID-19 Resource Center. Small molecules and antibodies make up the lion’s share of therapeutics in the clinic for COVID-19 (see Daily Chart).
Separately, FDA reported shortages of two drugs that have been repurposed for COVID-19 -- the antibiotic azithromycin and malaria drug hydroxychloroquine.
Hydroxychloroquine has been touted by President Donald Trump as a COVID-19 therapeutic “sent from heaven;” however, efficacy data for the therapy, which has well-documented toxicities, have been inconclusive (see “Debate Over Malaria Drugs for COVID-19 Illustrates White House Conflicts”).
Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus.