Friday, October 07, 2022
Merck, known as MSD outside the United States and Canada, and Ridgeback Biotherapeutics today issued the following announcement regarding data from two real-world evidence studies evaluating LAGEVRIO™ (molnupiravir), an investigational oral antiviral COVID-19 medicine. The first study, PANORAMIC, was conducted by the University of Oxford in the UK in highly-vaccinated adults mostly less than age 65 during the period when the circulating SARS-CoV-2 variant was predominantly Omicron. The second study, Clalit, was conducted by investigators in Israel in mostly older adults with underlying chronic health conditions that make them vulnerable to severe COVID-19 disease, also when Omicron was the most dominant strain. The PANORAMIC pre-print was published today and the Clalit pre-print was published last week. Additionally, Merck is reporting results from a recent carcinogenicity study in transgenic mice, which demonstrated that LAGEVRIO was not carcinogenic at any dose tested.
Preliminary results from the PANORAMIC study
The PANORAMIC study, a UK-based clinical trial sponsored by the University of Oxford, included 25,783 participants who were randomized to open label treatment with LAGEVRIO plus usual care (n=12,821) or usual care alone (n=12,962); mean age of participants was
56.6 years. Primary outcome data were available in 25,000 (97%) participants. Nearly all (>98%) participants were vaccinated, with approximately 95% receiving three or more doses of a SARS-CoV-2 vaccine. In the preliminary analysis, the primary endpoint of reduction of hospitalizations and deaths within 28 days of randomization, compared to usual care, was not met; 0.8% of patients in both the LAGEVRIO group (n=103/12,516) and the usual care group (n=96/12,484) were hospitalized or died in the first 28 days.
On secondary objectives, LAGEVRIO was associated with improvement on a range of measures compared to usual care. The observed median time to first self-reported recovery (the main secondary endpoint) was 6 days shorter in the LAGEVRIO group; the median time to first recovery was 9 days on LAGEVRIO (range 5-23 days) vs. 15 days on usual care (range 7 to not reached). Following adjustment for age and baseline comorbidity, there was a substantial estimated improvement of 4 days in time-to-first recovery in the LAGEVRIO group vs. usual care group (10.4 days vs. 14.5 days; treatment benefit ratio 1.36 (95% Bayesian credible interval (BCI) 1.3-1.4). The finding on time-to-first recovery was consistent for LAGEVRIO across key subgroups. Secondary objectives were not adjusted for multiplicity.
Results from the Clalit study
In this observational, retrospective cohort study, LAGEVRIO was associated with a lower rate of hospitalizations and mortality due to COVID-19 in patients 65 years and above, but not in younger adults. In patients 65 years of age and above (n=13,569), hospitalizations related to COVID-19, the primary endpoint, occurred in 18 LAGEVRIO-treated patients (74.6 per 100,000 person-days) and in 513 untreated patients (127.6 per 100,000 person-days); adjusted hazard ratio (HR) for hospitalization was 0.55 (95% confidence interval (CI), 0.34 to 0.88). The secondary endpoint of death due to COVID-19 in this same age group occurred in 4 of 845 LAGEVRIO-treated and 137 of 12,724 untreated patients; adjusted HR=0.26 (95% CI, 0.10 to 0.73).
In patients 40 to 64 years of age (n=6,229), hospitalizations related to COVID-19, the primary endpoint, occurred in 8 treated patients (125.8 per 100,000 person-days) and
97 untreated patients (49.1 per 100,000 person-days), and adjusted HR for hospitalization was 1.80 (95% CI, 0.86 to 3.77). The secondary endpoint of death due to COVID-19 in this same age group occurred in 4 of 224 LAGEVRIO-treated and 7 of 6,075 untreated patients; adjusted HR=12.82 (95% CI, 3.41 to 48.17). All four deaths in the LAGEVRIO-treated group occurred in patients 60-64 years of age.
“The totality of the data from both PANORAMIC and Clalit give us critical insights into the ways certain patients may benefit from treatment with LAGEVRIO. These data also emphasize the critical need and value for LAGEVRIO in the treatment of mild to moderate COVID-19 for appropriate high-risk patients. Most significantly, the Clalit study reinforces what the Phase 3 MOVe-OUT study demonstrated - a reduction in hospitalizations and mortality in an older population at high risk for progression to severe disease, where a clinically meaningful benefit was observed,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “These findings, particularly with regard to symptomatic improvement seen in a secondary objective in PANORAMIC and the reduction in hospitalization and death rates seen in the older part of the patient population in Clalit, further support the urgent need for global access to LAGEVRIO for the treatment of COVID-19 in appropriate high-risk patients.”
“With the continuing uncertainty about potential severity of emerging variants, we are pleased that the real-world data from Israel showed that, in an older part of the study population that experienced more hospitalizations, rates of hospitalization and death were reduced in patients taking LAGEVRIO. Also notable is the substantial reduction in time to symptom resolution observed on a secondary endpoint in PANORAMIC even when background hospitalization rates were low. The observed six-day improvement symptom resolution in the PANORAMIC study is an important finding as we look for ways to further reduce the burden of this virus. As studies begin to assess how this medicine could potentially treat other significant illnesses with pandemic potential, we will remain steadfast in our commitment to ensuring global access to this important treatment,” said Wendy Holman, chief executive officer, Ridgeback Biotherapeutics.