In leaked results from a University of Chicago study, Gilead Sciences Inc.’s antiviral remdesivir showed large improvements in some patients with the most severe form of COVID-19, the respiratory disease caused by SARS-CoV-2.
Out of an initial 125 patients who received the drug in the trial, one of two Phase III clinical programs being conducted in the US by the firm, 113 had severe forms of the disease, but “nearly all patients discharged in less than a week." Researchers at the University’s Medicines School noted “rapid recoveries” with the experimental treatment, according to leaked findings first reported by STAT news.
One of Gilead's US studies is for patients with severe symptoms, meaning they have been hospitalized due to confirmed PCR coronavirus test results, and have experienced severe respiratory syndromes that require supplemental oxygen. The studies, along with others in China, have attracted a lot of attention given the urgent need for effective and quickly available drugs in the global pandemic. (Also see "'Peoples' Hope' Remdesivir Results Due Soon - What To Look For?" - Scrip, 9 Apr, 2020.)
The large-scale University of Chicago study involves 152 sites across the US, with a target of 2,400 patients to be enrolled, and started on 6 March 6 with expected completion by May.
Patients are being given standard of care along with remdesivir – participants who are not mechanically ventilated will receive continued standard of care together with remdesivir 200mg on Day 1 followed by 100mg on the following four days (five-day treatment) or nine days (10-day treatment), and participants who are mechanically ventilated will receive standard care and 10-day treatment.
The primary endpoint is odds of improvement in the ordinal scale between the treatment groups, which is ranked in seven categories from one (death) to seven (discharge from hospital).
The UChicago study early results prompted investors to flock to Gilead shares, pushing the price up by 16% in after-hours trading on 16 April. In response, Gilead commented only that “what we can say at this stage is that we look forward to data from ongoing studies becoming available.”
However, some observers say there are still uncertainties over results that have emerged so far. The “biggest challenge with interpreting this data is there is no comparator arm in this study,” noted one expert, quoted on Chinese social media platform WeChat. He added that “there is also no mention of viral loads going negative.”
Comparing the study results to earlier results from a smaller sized study on the compassionate use of remdesivir, published in the New England Journal of Medicine, the expert asked: “The majority of the 113 patients in this GILD-run severe [disease] study got discharged at the University of Chicago – we can’t ignore that. But, what percentage of those patients should have been discharged?”
The design for the Gilead study, which includes both patients on non-invasive oxygen and medical ventilation, explicitly excludes patients who are medically ventilated five days, making it hard to determine whether the “majority of the patients” who were discharged were medically ventilated or not. (Also see "Gilead's Compassionate Use Data Promising, But Imminent COVID-19 Treatment Shift Unlikely" - Pink Sheet, 13 Apr, 2020.)
In comparison, the study published in the NEJM explicitly stated that “25 of 53 patients (47%) had been discharged (24% receiving invasive ventilation [8 out of 34 patients] and 89% [17 out of 19 patients] receiving noninvasive oxygen.”
China Halt Not Due To Efficacy
Due to a lack of patients, two remdesivir Phase III studies in China - the first to be started worldwide and conducted in epicenter Wuhan - have been suspended. The reasons given were that COVID-19 “has been controlled well at present” and “no eligible patients can be recruited." (Also see "Coronavirus Update: Remedesivir China Trials Halted, Witty To Spearhead WHO's Vaccines Efforts" - Scrip, 16 Apr, 2020.)
The two trials, one in severe patients, could have been halted earlier if an interim result due in mid-March had shown superior efficacy, noted the expert. China is seemingly determined to take the lead in accelerating new treatments and vaccines to fight the outbreak, and as the first country to be hard hit, has already approved three medicines for COVID-19, but all are traditional herbal medicines. (Also see "China Approves First Coronavirus Drugs, Rushes Two Vaccine Trials" - Pink Sheet, 15 Apr, 2020.)
But the expert argued on WeChat that the halt of the China remdesivir studies due to patients shortages rather than efficacy may indicated that the antiviral, despite billed as the “People’s Hope” in China, has not yet achieved efficacy so overwhelming that it was worthy of an earlier study halt on these grounds. “Remdesivir needed to show over 60% efficacy against placebo in order to stop at interim, clearly it didn’t achieve that,” he stated.
While the molecule "is not a silver bullet” this doesn’t mean that it is not effective, the expert said. "We should remain cautiously optimistic."