Remdesivir had received regulatory approvals or temporary authorisations to treat COVID-19 in approximately 50 countries including India. The drug has been pre-qualified by WHO.
The World Health Organisation (WHO)'s Solidarity trial has found that Remdesivir, the antiviral drug that's widely prescribed for treating COVID-19, has no substantial effect on overall death rate or mortality, initiation of ventilation and duration of hospital stay.
The data of the Solidarity trial have not yet been peer-reviewed or published in a scientific journal, but was uploaded as a preprint at medRxiv.
Remdesivir had received regulatory approvals or temporary authorisations to treat COVID-19 in approximately 50 countries including India. The drug has been pre-qualified by the WHO.
With the Solidarity trial casting a shadow on the use of Remdesivir, below is an explainer on the issue:
What does the Solidarity trial data say?
WHO began the trial in March 2020. The trial is a multi-country, open-label randomized trial. Open-label means both the researchers and participants know which drug is being given to participants.
The protocol was designed to involve hundreds of potentially over-stressed hospitals in dozens of countries. The patients who were part of the trial were hospitalized with a diagnosis of COVID-19. Of the 11,266 adults who were randomised in 405 hospitals across 30 countries, 2,743 people were given Remdesivir and 2,708 were part of control group or usual care.
Of the 2,743 patients on Remdesivir, 301 died, and of 2,708 under control group, 303 died at 28 days. The 28-day mortality rate was 11 percent for patients on Remdesivir and 11.2 percent for control group -- a difference of only 0.2 percent, which is considered statistically insignificant.
How did recent NIAID data differ from the Solidarity trial?
To be sure, the Solidarity trial results didn't come as a surprise. Remdesivir did not show statistically meaningful reduction in mortality in hospitalised patients in previous studies as well.
The data from the ACTT-1 trial on 1,062 patients by the US government's National Institute of Allergy and Infectious Diseases (NIAID) published in the New England Journal of Medicine (NEJM) has found that hospitalized patients with COVID-19 pneumonia who received Remdesivir recovered five days faster than patients receiving placebo at day 29, and had evidence of lower respiratory tract infection. The study is a double-blind, placebo-controlled study. In this study too there was no significant difference in death rate between those who received Remdesivir (11.4 percent) or placebo (15.2 percent).
However, the Solidarity trial revealed that were no material effects on ventilation initiation or time to discharge.
What are Gilead and others saying?
US-based Gilead Sciences has expressed concern that the data from the open-label global trial have not been under rigorous review.
Gilead said the emerging data appear inconsistent with more robust evidence from multiple randomized, controlled studies published in peer-reviewed journals validating the clinical benefit of Veklury (Remdesivir)
"We are concerned that the data from this open label global trial have not undergone the rigorous review required to allow for constructive scientific discussion, particularly given the limitations of the trial design," Gilead added.
Others like Kiran Mazumdar-Shaw, Chairperson of Biocon, described the design of the WHO Solidarity trial for Remdesivir as "flawed".
Shaw tweeted saying that Remdesivir didn't cut hospital stay or mortality in Covid patients due to WHO's "flawed trial design as it needs to be used early as it stops viral replication."
"Remdesvir needs to be used within the first 10 days to have any effect. Using it thereafter is meaningless as the viral load diminishes rapidly after the first week," Shaw added.
Syngene, the contract research subsidiary of Biocon, has a licensing agreement with Gilead to manufacture and distribute Remdesivir in 127 countries including India.
Will there be review of Remdesivir clinical protocol?
Remdesivir was approved for use in people who were sick enough to need supplemental oxygen or breathing support, as per ICMR protocol, but has now emerged as standard of care for treating hospitalised Covid-19 patients.
"Currently there is no evidence that Remdesivir works, it's an expensive medicine, perhaps it may reduce the hospital stay of the patient," said Dr. Rahul Pandit, Senior Intensive Care Specialist and Director of Critical Care Medicine & ICU at Fortis Hospital.
Pandit, who is a member of the Maharashtra government's task force on COVID-19, said there is a possibility of Remdesivir clinical protocol being updated.
The price of Remdesivir ranges from Rs 2,900 - Rs 5,400 per dose, with patients typically requiring about six doses. Indian companies have built large capacities capable of producing about 6-7 lakh doses. Cipla, Hetero, Dr Reddy's, Zydus Cadila, Jubilant Life Sciences, Syngene are Indian companies with licenses to manufacture and distribute Covid vaccines.
First Published on Oct 16, 2020 07:12 pm