Antivirals EUA
October 13, 2021
In recent news, Merck and Ridgeback has been hailing an oral anti-viral drug against Sars-CoV-2 that can cut the hospitalization and death rates in half according to their news posted on Oct 1, 2021 on their website. Apparently, the drug was doing so well in their clinical trials that they prematurely stopped the Phase 3 trial, MOVe-OUT, since the interim results were so strong and asked for EUA. This trial had been conducted globally, so not just in the United States, and had more than 170 planned sites.
According to their results, their investigational oral anti-viral drug called Molnupirvair@ was found to reduce the risk of hospitalization or death by at least 50% as compared to placebo for patients who had mild or moderate COVID-19 infection. They further report that at an interim analysis, 7.3% of patients who received Molnupirvair@ were hospitalized through day 29 (28/385) as compared to 14.1% of patients who received a placebo who were hospitalized or who had died (53/377) with a p-value of 0.012. As we can see, they obtained this 50% difference between these percentages that were obtained from relative risk calculations, which makes sense since it was a prospective trial or we can assume.
What we do not know is how many interim analyses did they have prior to this interim result. As statisticians, we would like to know how many planned interim analyses they had planned altogether, and also how many may have occurred before the one in which they made this decision to prematurely stop their trial for this drug. What they said is this: “The planned interim analysis evaluated data from 775 patients who were initially enrolled in the Phase 3 MOVe-OUT trial on or prior to Aug. 5, 2021. At the time of the decision to stop recruitment based on the compelling interim efficacy results, the trial was approaching full recruitment of the Phase 3 sample size of 1,550 patients, with more than 90% of the intended sample size already enrolled.” Also, they gave further information about eligibility, efficacy, and incidence of adverse events (AEs).
“Eligibility criteria required that all patients had laboratory-confirmed mild-to-moderate COVID-19, with symptom onset within 5 days of study randomization. All patients were required to have at least one risk factor associated with poor disease outcome at study entry. Molnupiravir reduced the risk of hospitalization and/or death across all key subgroups; efficacy was not affected by timing of symptom onset or underlying risk factor. Additionally, based on the participants with available viral sequencing data (approximately 40% of participants), molnupiravir demonstrated consistent efficacy across viral variants Gamma, Delta, and Mu. The incidence of any adverse event was comparable in the molnupiravir and placebo groups (35% and 40%, respectively). Similarly, the incidence of drug-related adverse events was also comparable (12% and 11%, respectively). Fewer subjects discontinued study therapy due to an adverse event in the molnupiravir group (1.3%) compared to the placebo group (3.4%).”
Although not a single statistical model is written in their writeup of their report on their website, we can only infer how they compared incidence between groups but wish they would have at least mentioned use of one statistical model. The incidence of any AEs in either group seems high and is not much lower in the study drug group and even the incidence of drug-related AEs were comparable. Not much is given to explain this but certainly FDA would be interested in this. It will be interesting to see if this drug can get EUA. The possibility is strong since there is not much out there to actually treat COVID-19 and also since this an oral and therefore, easy for patients to take.
Written by,
Usha Govindarajulu
Keywords:
COVID-19, anti-viral, Merck, clinical trail, Phase 3, interim analysis, EUA, FDA, Usha Govindarajulu
References
https://www.nature.com/articles/d41586-021-02783-1
