E-Paper
Promising antiviral trial hits roadblock
In India, only the angti-malarial drug hydrocxycloroquine has received the ICMR’s approval for treatment of severely ill Covid-19 patients, but some hospitals have begun giving plasma therapy as part of registered clinical trials.
What had been thought to be a promising antiviral drug to treat the coronavirus disease (Covid-19) was found to offer no benefits to patients or prevent death, according the draft findings of clinical trials in China that were accidentally published by the World Health Organisation (WHO) on its website on Thursday.
“The Chinese study, which will soon be published, was inconclusive. We have to wait for larger studies,” said Dr Soumya Swaminathan, chief scientist at the Geneva-based WHO, told HT.
Remdesivir, an experimental drug developed by US-based biopharmaceutical company Gilead Sciences Inc. displayed no positive impact in the clinical trials conducted in China, according to the trial findings that caused shares of the company to drop sharply.
“In this study of hospitalised adult patients with severe Covid-19, [which] was terminated prematurely, remdesivir was not associated with clinical or virological benefits,” said the draft result of the first randomised clinical trial of remdesivir, which was posted online by the WHO and first accessed by Stat, a health-oriented news website.
The agency quickly took the report off its website, saying it had posted the findings by mistake and that the manuscript was still under peer review. Gilead Sciences told Stat that the document had mischaracterised the study.
In a statement, WHO spokesperson Daniela Bagozzi, said: “A draft manuscript was provided by the authors to WHO and inadvertently posted on the website and taken down as soon as the mistake was noticed. The manuscript is now undergoing peer review and we are waiting for a final version before WHO comments on it.”
The trial found remdesivir did not improve the condition or prevent death when administered to 237 Covid-19 patients.
The drug was given to 158 patients, whose progress was then compared with 79 others given a placebo. A month later, 13.9% of the patients given the drug died, compared to 12.8% of those on the placebo. “Remdesivir was not associated with clinical or virological benefits,” said the trial summary.
The trial was stopped early because of side effects, said the study. “Remdesivir was stopped early in 18 (11.6%) patients because of adverse effects, compared with 4 (5.1%) in the control group.” There were no details in the short report on the side effects that caused the trial to be halted.
Remdesivir, which inhibits viral RNA polymerases, has shown in-vitro activity against Sars-CoV-2, the virus that causes Covid-19. The drug had failed Ebola trials in Africa, and China had halted two trials for remdesivir, saying that there weren’t enough patients to fully enrol in the studies.
“Remdesivir is part of the WHO’s multi-country solidarity trial that is comparing four promising treatment options against standard care to assess their relative effectiveness against Covid-19. We were following it, but haven’t started use in India,” said Dr Yatin Mehta, chairman, Institute of Critical Care and Anaesthesiology, Medanta-the Medicity, where patients are being treated in Covid-19 isolation ward since March 4.
The other drugs being tested are chloroquine or hydroxychloroquine, lopinavir with ritonavir; and lopinavir with ritonavir plus Interferon beta-1a. Until there is sufficient evidence, the WHO cautions against physicians and medical associations recommending or administering these unproven treatments to patients with Covid-19 or people self-medicating with them.
India is a part of solidarity trial, but the Indian Council of Medical Research has not approved remdesivir for Covid-19 treatment in India. “A Gilead study found reduced oxygen support in about 68% of the Covid-19 patients, but it was an observational study of patients being treated with it on compassionate grounds, and {NOT} a clinical trial. There is not enough evidence to suggest it works, so when we have clinical evidence that shows it working then we will act accordingly,” said Dr. Raman Gangakhedkar, head, epidemiology and communicable disease division, ICMR.
A study of remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support,found clinical improvement in 68% patients, according to a Gilead Sciences-funded study published in The New England Journal of Medicine (NEJM) on April 10.
In India, only the angti-malarial drug hydrocxycloroquine has received the ICMR’s approval for treatment of severely ill Covid-19 patients, but some hospitals have begun giving plasma therapy as part of registered clinical trials.
India took the antivirals lopinavir and ritonavir off the Covid-19 treatment list after it was found to offer no benefit compared to standard care, according to a study published in the NEJM on March 18.
In the absence of a specific treatment for Covid-19, most clinicians depend on using antimalarial hydrocxycloroquine along with an antibiotic to treat people hospitalised in isolation wards.
“It is all we have. All patients in isolation wards are given a combination of hydroxychloroquine twice a day and azithromycin once a day for five days, and it has been tolerated well. No adverse reactions have been reported,” said Dr Mehta.
Gilead Sciences shares fell 4.34% to $77.78 on the Nasdaq following the report’s publication.
In a statement, Gilead Sciences said the study had been terminated early because of low enrolment Stat news and “underpowered to enable statistically meaningful conclusion.”
“There are multiple ongoing Phase 3 studies that are designed to provide the additional data needed to determine the potential for remdesivir as a treatment for COVID-19. These studies will help inform whom to treat, when to treat and how long to treat with remdesivir. The studies are either fully enrolled for the primary analysis or on track to fully enroll in the near future,” the statement said .
