Resist the urge to regulate in step with USFDA
Premium- The US drugs regulator approved a controversial new anti-viral pill for Covid on Thursday. India must act with caution.
The United States Food and Drug Administration (USFDA) gave an emergency use authorization (EUA) to US drugmaker Merck for anti-viral pill molnupiravir in the treatment of mild-to-moderate coronavirus infection on Thursday. Molnupiravir is approved for use in adult patients who test positive and are at high risk of progressing to severe disease leading to hospitalization and even deaths. The USFDA statement makes it clear that the new pill must be prescribed only when other USFDA-authorized treatments are inaccessible or not clinically appropriate.
In India, molnupiravir is being evaluated by a Subject Expert Committee (SEC) that advises the country’s drugs regulator — the Drugs Controller General of India (DCGI) — on product approvals. Data from clinical trials on Indian subjects are with the SEC. Sun Pharma, Dr Reddy’s and Cipla are already licensed by Merck to manufacture and supply this drug in India and other low and middle-income countries.
The SEC has reportedly asked drug companies why accelerated approval must be granted in light of the relatively low efficacy of the drug. It also sought a risk mitigation plan in case of an adverse event. The nod for molnupiravir in the US follows close on the heels of the approval for Pfizer’s Paxlovid, comprising two co-packaged drugs nirmatrelvir and ritonavir. Paxlovid is the first USFDA-approved oral treatment for Covid-19. It has shown better efficacy than molnupiravir in trials.
With a third wave led by a new variant of the virus turning out to be a real threat in India, the imperative, understandably, is to provide as many options as possible to healthcare professionals to keep patients out of hospitals. All the same, for several years now, it has become increasingly evident that granting approvals based on the decisions taken by regulatory agencies in other countries is a job half-done, given the weak after-market regulatory oversight here. India’s system of keeping tabs on the side-effects of marketed health products—whether drugs, devices or vaccines—is woefully inadequate relative to the population. Before rushing to approve molnupiravir, the DGCI must ensure the Indian ground realities are taken into account and the benefits versus risks specific to the Indian conditions are adequately weighed in.
The pandemic has seen a surge in the prescription of drugs such as the anti-viral remdesivir, despite limited scientific evidence backing for its efficacy as a Covid treatment. In general, indiscriminate prescription of antibiotics is one reason why India has turned into a hotbed of anti-microbial resistance. Indian patients often stop treatment mid-way once they feel better, contributing to the scourge of antibiotic resistance. In the case of molnupiravir, such behaviour could raise the spectre of the spread of mutations of the virus.
For new drugs and vaccines, and safety concerns flagged for a drug being marketed, the Indian drug regulatory system attaches considerable weight to the decisions of better-resourced regulators such as the USFDA. Molnupiravir’s controversial run to the EUA finish line cannot be taken lightly. For starters, there was significant drop reported in relative risk reduction in hospitalization and death—from 50% to 30%—between the interim analysis of the phase 3 clinical trial data publicised by Merck in October and the updated analysis in November. Such a change in efficacy potentially alters the calculus of risk versus benefit for any drug approval. The committee of experts that evaluated the case for USFDA had debated this issue in November. Its potential to harm the foetus in pregnant women was also raised. As were concerns about the danger, however minor, of mutations in the virus in patients who do not complete the full course. The committee’s final vote in the pill’s favour was narrow at 13-10.
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The USFDA approval is subject to Merck maintaining a pregnancy surveillance programme, with monthly reports on outcomes in patients exposed to molnupiravir during pregnancy. This seems difficult in the Indian setting, given the middling to poor record of the Indian drug industry in sharing post-market surveillance or adverse events data with the regulator.
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