Reporter |
Editor |Xie Xin
On September 28, MSD China officially announced that MSD and China National Pharmaceutical Group Corporation jointly announced a cooperation framework agreement regarding the anti-COVID-19 oral drug Molnupiravir (molnupiravir) in China. According to the terms of the cooperation framework agreement, after Molnupiravir is approved in China, MSD plans to grant China National Pharmaceutical Group Corporation the exclusive distribution and import rights of the drug within China.
At the same time, MSD and China National Pharmaceutical Group Corporation will evaluate the feasibility of technology transfer so that the drug can be manufactured, supplied, and commercialized within China. China National Pharmaceutical Group Corporation's subsidiary, China Biologic Products, will be responsible for advancing the localized production and supply of the drug after receiving the technology transfer of MSD’s Molnupiravir. To date, the drug has not yet been approved in China.
Molnupiravir is an oral small-molecule treatment for COVID-19. In June this year, Anna Tian, President of MSD China, said in an interview with The Paper that the COVID-19 drug Molnupiravir had submitted its application for market approval in China and would expand its supply globally. "Regarding Molnupiravir, we have maintained active communication with regulatory authorities. We have now completed the rolling submission required by the Center for Drug Evaluation of the National Medical Products Administration and are awaiting further feedback. We hope to bring this drug to Chinese patients in urgent need as soon as possible," Anna Tian introduced.
Typically, reaching a commercial distribution and logistics partnership with a local distributor is seen as a precursor to the domestic commercial sale of imported drugs. Therefore, this collaboration between the two parties may indicate that this COVID-19 oral medication is not far from receiving approval.
As of now, there are two drugs approved for the treatment of COVID-19 in China: Pfizer's oral COVID-19 drug Paxlovid (Nirmatrelvir Tablets/Ritonavir) and Real Biotech's Azvudine.
Currently, the partners for both Paxlovid and Azvudine have been confirmed. On March 9 this year, Pfizer and Sinopharm announced that they had signed a supply agreement for the COVID-19 treatment drug Paxlovid. General Technology Sinopharm will be responsible for the commercial operations of Pfizer's COVID-19 treatment drug Paxlovid in the Chinese mainland market during the term of the agreement.
On July 27, Fosun Pharma, the owner of the commercial rights to Azvudine, announced that its subsidiary, Fosun Pharma Industry, had signed a strategic cooperation agreement with China National Pharmaceutical Group Corporation (Sinopharm) in Shanghai. Both parties will leverage their respective resource advantages to undertake the commercialization and supply chain operations of Genuine Biotech's Azvudine tablets in China.
To date, globally, Molnupiravir has received marketing authorization or emergency use authorization in more than 40 countries and regions, including the United States, the European Union, Australia, Japan, South Korea, as well as Hong Kong, China and Taiwan, China. As of the end of August this year, MSD has supplied more than 8.6 million courses of Molnupiravir to over 30 markets worldwide, treating more than 1.8 million patients.
Notably, this collaboration marks the first time that an overseas oral COVID-19 medication has considered localized production in China.
In terms of efficacy and safety, at the end of 2021, MSD announced the Phase III clinical research report of Molnupiravir, which showed that it could reduce the risk of hospitalization/death by 30% (6.8% vs 9.7%). This study, named MOVe-OUT (MK-4482-002) (NCT04575597), was a global multi-center, randomized, double-blind, placebo-controlled Phase III clinical trial. The participants were non-hospitalized adult patients with mild to moderate COVID-19 confirmed by laboratory tests, who had not been vaccinated against COVID-19 before enrollment and had at least one risk factor associated with poor disease prognosis (elderly (>60 years old), active cancer, chronic kidney disease, chronic obstructive pulmonary disease, obesity, severe heart disease, or diabetes), and had symptoms appearing within five days prior to randomization.
The primary efficacy endpoint of MOVe-OUT was to evaluate the efficacy of Molnupiravir (800mg, twice daily) by comparing the percentage of participants hospitalized and/or deceased from randomization through Day 29 between the Molnupiravir group and the placebo group. In the interim analysis report, the risk of hospitalization or death in the Molnupiravir group was reduced by approximately 50%. In the complete randomized analysis report (n=1433), the risk of hospitalization or death in the Molnupiravir group was lower as of Day 29. Among patients, 9.7% (68/699) in the placebo group versus 6.8% (48/709) in the Molnupiravir group showed an absolute risk reduction of 3.0% (95% Confidence Interval: 0.1, 5.9), with a relative risk reduction of 30%.
In terms of safety, consistent with earlier clinical trials, no safety issues were found with Molnupiravir, and there was no evidence of clinically significant abnormalities in laboratory test results. The incidence of all adverse events (AEs) in the Molnupiravir group and the placebo group was comparable (30.4% and 33.0%, respectively). The incidence of drug-related adverse events was also similar (8.0% and 8.4%, respectively), and a lower proportion of patients in the Molnupiravir group discontinued treatment due to adverse events compared to the placebo group (1.4% vs. 2.9%). As of Day 29, no deaths were reported in the Molnupiravir group, while there were 9 deaths reported in the placebo group. After Day 29, there were 3 additional death reports in the placebo group due to adverse events, and 1 death report in the Molnupiravir group.
In addition, there is currently a study named MOVE-AHEAD evaluating the post-exposure prophylactic effect of Molnupiravir. This is a global multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial aimed at assessing the efficacy and safety of Molnupiravir in preventing household transmission of COVID-19.