Hidden clinical trial results no barrier to $6.6 billion sales of Covid drug
The Covid drug molnupiravir (Lagrevio) has continued to rack up sales now totalling $6.6 billion against a backdrop of hidden clinical trial results and underwhelming evidence from published trial outcomes.
In the latest episode of the saga, a post-exposure prevention study of the drug has just failed on its primary endpoint.
UPDATE 24 February 2023: European regulators refused to recommend the approval of molnupiravir by the EMA, saying that there is not enough evidence it works in patients.
Back in August 2022, when global sales reportedly stood at 'only' $3.2 billion, a independent researchers warned in a preprint that the results of 12 clinical trials of molnupiravir run by generics manufacturers in India had not been made public. As of September 2022, approximately one-third of the global data on molnupiravir remained unpublished.
The preprint authors also flagged suspiciously rapid participant recruitment and the “almost unprecedented” absence of any severe adverse events whatsoever in a trial that included 1,218 patients, suggesting that something was amiss.
The publication of possible negative results from those trials would likely have damaged the sales prospects of the generics manufacturers running the research. The Indian trials collectively aimed to recruit a total of 13,694 patients.
Evidence-based drug procurement?
Nonetheless, sales of the Covid-19 pill continued apace. Over the past seven months, an additional $3.4 billion of the drug have been sold worldwide.
According to reporting by Fierce Pharma:
"[T]he pill generated more than $6.6 billion in sales over its first five quarters on the market, despite mounting evidence of its limited effectiveness."
"Today, of the 2.9 million courses of Lagevrio delivered to the U.S., only 1.1 have been administered, according to the Department of Health and Human Services."
What drives trial reporting?
The molnupiravir saga highlights how difficult it can be to gain a comprehensive overview of a treatment's benefits and harms when different players run trials in different countries.
Manufacturer Merck has a near-perfect track record of compliance with both European (99.8%) and American (100%) trial transparency laws.
This strong track record is typical of major pharma companies in Europe and North America: If there is a legal requirement to make trial results public, they do so. (Note that Merck cannot compel Indian companies to disclose their trial results.)
The picture is clearly different when Indian generics manufacturers run trials within India.
Disclosure requirements in India are different, legal compliance even by large players is often weak, and drug regulators and courts frequently turn a blind eye to legal violations.
(To be fair, regulators in Europe and in the U.S. have also been very weak on enforcing trial reporting requrements. On both sides of the Atlantic, Big Pharma's strong compliance so far appears to have been driven by reputational concerns rather than by worries about regulators imposing fines. Generics companies in India presumably have lower name recognition and may feel less need to protect their reputations.)
Lessons learned?
The medical research landscape is now truly global and highly diverse. At the same time, rules on trial disclosure continue to be set and enforced at the national level.
There are no easy solutions here. However, as a useful first step, regulators and agencies charged with drug procurement should be more alert to unreported clinical trials and resulting gaps in the evidence base.
Arguably, the Indian generics manufacturers' apparently deliberate decision not to publish the results of their trials should have raised red flags at a far ealier stage.
In future, decision-makers may want to think twice before spending an additional $3.4 billion on a drug with glaring evidence gaps.
Note: The preprint on missing molnupiravir trials that is flagged above has since evolved into a peer-reviewed publication. Previous TranspariMED coverage of the molnupiravir saga can be found here.