Merck and Ridgeback Pharmaceuticals’ molnupiravir is drawing heightened public interest due to its recent data in mild-to-moderate Covid-19. However, Pfizer, Roche and Atea Pharmaceuticals are hot on molnupiravir’s heels with their own respective data reveals expected in the next few months.
Pfizer trials’ primary completion imminent
Pfizer’s PF-07321332 tablet is a protease inhibitor, designed to prevent SARS-CoV-2 from replicating. Phase I data shows PF-07321332 led to more than five times the 90% effective concentration (EC90) needed for antiviral activity over the entire five-day treatment period, according to a 28 July presentation.
There are currently three PF-07321332 trials listed on ClinicalTrials.gov. Of the three, the most relevant is the Phase II/III trial (NCT04960202) combining PF-07321332 with antiretroviral capsule ritonavir in infected people who do not require hospitalisation but are at increased risk of developing severe disease.
Phase I data shows PF-07321332 led to more than five times the 90% effective concentration (EC90) needed for antiviral activity.
The 3,000-patient, placebo-controlled trial has a primary endpoint of proportion of participants hospitalised due to Covid-19 or death from any cause. The trial has a 26 November primary completion date.
The second Phase II/III trial (NCT05011513) is studying the same combination in people who are infected but at low risk of progressing to severe illness. This 1,140-patient trial has a primary completion date of 18 October. In both Phase II/III trials, the combination is taken orally every 12 hours for five days. Meanwhile, in a Phase III trial (NCT05047601), the combination is under investigation in the post-exposure setting, with the study recruiting people who are asymptomatic household contacts to a symptomatic patient. It has a 25 December primary completion date.
Atea, Roche’s antiviral data expected soon
Direct-acting antiviral tablet AT-527, being jointly developed by partners Atea and Roche, is designed to target two functional domains in SARS-CoV-2’s RNA polymerase nsp12. In a Phase II study (NCT04396106) recruiting hospitalised patients with moderate Covid-19, sustained decrease in viral load was observed, according to a 12 August presentation.
The 220-patient Phase II MOONSONG trial (NCT04709835) recruiting mild-to-moderate Covid-19 patients is still ongoing. While its ClinicalTrials.gov listing shows it has a primary completion date of 22 September, interim virology data is expected sometime before the end of the year. MOONSONG is investigating the magnitude of SARS-CoV-2 RNA reduction caused by AT-527 versus placebo.
While MOONSONG data is yet to be read out, the Phase III MORNINGSKY trial (NCT04889040) was initiated with results also expected in 2H21. The 1,386-patient, placebo-controlled trial is investigating AT-527 taken twice daily for five days, and a primary endpoint of the time it takes to alleviate or improve symptoms. ClinicalTrials.gov lists MORNINGSKY with a primary completion date of 17 November.
In the Phase III follow-up trial MORNINSPRING (NCT05059080), MORNINGSKY participants are further monitored for an additional six months. Also on the cards is the initiation of the Phase III MARJORAM study, investigating AT-527 in the post-exposure setting.
Atea and Roche’s collaboration was announced in October 2020. If the tablet secures regulatory support, Atea will drive distribution in the US, with the potential support of Roche’s Genentech, with Roche managing supplies outside of the US.
Merck, Ridgeback ahead in regulatory race
With Merck and Ridgeback reporting positive interim data from its Phase III MOVe-OUT trial (NCT04575597), it is ahead of other oral mild-to-moderate Covid-19 assets in securing regulatory support. On 1 October, the companies said molnupiravir reduced the risk of hospitalisation or death in at-risk, nonhospitalised patients with mild-to-moderate symptoms. MOVe-OUT data shows that 7.3% of molnupiravir patients were either hospitalised or died through day 29, compared with 14.1% in the placebo arm.
On 22 September, this news service reported that if molnupiravir is authorised, physicians themselves will determine treatment eligibility based on each patient’s risk-benefit profile. There is likely to be uncertainty around the optimal timing of using molnupiravir in practice because there is the need to use the oral capsule as early as possible owing to its mechanism as an antiviral.
There is likely to be uncertainty around the optimal timing of using molnupiravir in practice.
Small molecules like molnupiravir, which works by inhibiting RNA virus replication, are less specific and run the risk of off-target side effects, this news service reported 29 January. Assuaging these concerns is the fact that molnupiravir is only designed for short-term use: twice-daily for five days.
Merck has been manufacturing molnupiravir while MOVe-OUT was still ongoing, with the company expecting to make 10 million treatment courses by the end of the year. On 9 June, Merck announced it entered a procurement agreement with the US for approximately 1.7 million molnupiravir courses.
As with the other two oral drugs, molnupiravir is also under investigation in a Phase III post-exposure trial (NCT04939428) dubbed MOVe-AHEAD. This trial has a primary completion date of April 2022.