Merck & Co. Inc. has shut down two COVID-19 therapy development studies while moving another into a phase III trial.
In its collaboration with Ridgeback Biotherapeutics LP, Merck decided to stop its study of hospitalized COVID-19 patients and continue studying outpatients in the ongoing phase II/III trials of oral molnupiravir vs. placebo. The decision stems from an interim analysis of the phase II, dose-finding portion of the oral therapeutic’s ongoing study
Merck also decided to discontinue development of MK-7110 for treating hospitalized COVID-19 patients. Merck acquired MK-7110, a fusion protein with anti-inflammatory effects, through its $425 million acquisition of privately held, Rockville, Md.-based Oncoimmune Inc. in November.
In the Merck-Ridgeback program, which found viral load reduction for both studies, the phase II/III MOVe-IN study of molnupiravir (MK-4482/EIDD-2801) in hospitalized patients will not proceed because data showed it was unlikely to demonstrate a clinical benefit. Playing into the decision is the patient base, which generally had a longer duration of symptoms before entering the study.
The phase II portion enrolled 304 participants randomized 1-to-1-to-1-to1 to receive molnupiravir 200 mg, 400 mg, 800 mg or placebo twice daily for five days. The primary efficacy endpoint was to evaluate the molnupiravir vs. placebo as assessed by the rate of sustained recovery from randomization through day 29.
MOVe-OUT, the study of outpatients, is randomized, placebo-controlled, double-blinded, multisite study with a primary efficacy objective of comparing molnupiravir to placebo by assessing the percentage of patients who are either hospitalized and/or die from the time they are randomized through day 29. Part 1 saw 302 participants with symptom onset seven days before randomization receive molnupiravir 200 mg, 400 mg, 800 mg or a placebo.
While the percentage of patients who were hospitalized and/or died in Part 1 was lower in the combined molnupiravir-treated groups vs. the placebo arm, the number of reported events failed to provide a meaningful measure of clinical effect. Data from the interim analysis prompted the companies to proceed to phase III. The MOVe-OUT final data are not expected until September or October.
Much of the study displays a “disappointing clinical execution” and is “mind boggling,” according to Evercore ISI analyst Umer Raffat, who asked on April 15 why the antiviral had no clinical benefit in hospitalized patients when Gilead Sciences Inc.’s remdesivir had a 26% to 55% reduction in mortality. Raffat concluded that the Merck-Ridgeback study was on top of the standard of care, remdesivir, for example.
“Even then, it begs the question: What was MRK’s survival data vs. placebo in patients who did NOT have background remdesivir?” Raffat wondered in a research note.
Raffat also thought recruiting only 300 patients was anemic and that patients may have been underdosed with the ribonucleoside analogue that inhibits multiple RNA virus replication.
In discontinuing MK-7110 development, Kenilworth, N.J.-based Merck is following the FDA’s March opinion that more data would be needed to support an emergency use authorization (EUA) for the therapeutics. More clinical trials, plus the manufacturing component, didn’t work well against the ticking clock as they would make MK-7110 unavailable until the first half of 2022.
This isn’t the first time this year Merck hit the brakes on COVID-19 vaccine programs. On Jan. 25, it said it was terminating its two COVID-19 vaccine programs, V-590 and V-591, because neither demonstrated convincing efficacy levels in phase I studies.
Covis misses with corticosteroid
Also experiencing a stumble is Covis Pharma Group, whose phase III trial of corticosteroid drug ciclesonide vs. placebo in non-hospitalized patients 12 and older with symptomatic COVID-19 infection produced data showing the treatment was not statistically significant.
The primary endpoint of the multicenter, randomized, double-blind, placebo-controlled, 400-patient study was the time of alleviation of COVID-19-related symptoms to being symptom-free for at least 24 hours by day 30.
The data demonstrated a treatment difference between ciclesonide (70.6%) and placebo (63.5%) in the percentage of patients with an improved time to alleviation of COVID-19 related symptoms.