DUBLIN – The most solid conclusion that can be drawn from a phase II trial of IMU-838 in hospitalized COVID-19 patients is that a reduction in the need for invasive ventilation is no longer a useful endpoint for trials of COVID-19 drugs.
The study randomized 233 hospitalized patients with moderate disease to receive either a twice daily dose of IMU-838 (vidofludimus calcium), an oral dihydroorotate dehydrogenase (DHOD) inhibitor, or placebo, over a 14-day treatment period. The primary endpoint was the proportion of patients without any need for invasive ventilation at any point throughout the 28-day study.
The efficacy of the drug on this measure was not evaluable, however, due to the trial’s extraordinarily low event rate. Of 204 participants analyzed, less than 1% of those enrolled required ventilation during the study, which, trial sponsor Immunic Inc. noted, was in marked contrast “to the relatively high rates of ventilation reported in the first COVID-19 wave in early 2020.” The outcome was consistent with other recent third-party trials, the company added.
The trial protocol allowed for physician’s choice of standard of care therapy. That, combined with the clinical experience developed in managing patients over the past 12 months, was the study’s undoing.
The study, which was conducted in 20 centers in the U.S. and Europe, also failed to demonstrate any difference between IMU-838 and placebo on two key secondary endpoints, 28-day survival and the need for ICU care. Immunic again attributed these outcomes to very low event rates. The 28-day mortality rate on the trial was less than 2%, while less than 4.5% of trial participants were admitted to ICU.
Immunic, of New York, nevertheless, claimed that the study uncovered signs of efficacy based on additional clinical, biochemical and virological parameters. Those on IMU-838 were more likely to achieve clinical recovery within 28 days – 71.3% of those on the drug (n=57) achieved this endpoint, as compared with 66.7% of those in the control arm (n=58). The proportion of patients reaching clinical improvement at 28 days was 90.9% for those on drug (n=90), as compared with 87.4% for those on placebo (n=90). It also reported that, for high-risk patients, the 75% probability of reaching clinical improvement was accelerated by 3.8 days for those on drug as compared to those on placebo.
Investors took a less sanguine view. The stock (NASDAQ:IMUX) was off by 17% during premarket trading Feb. 17. A final analysis of the full dataset involving 223 patients is expected in the second quarter.
IMU-838 has the same immunomodulatory mechanism as Aubagio (teriflunomide), a drug marketed by Paris-based Sanofi SA, which has attained blockbuster status in multiple sclerosis on the basis of its oral dosing and its benign side effect profile. Its target, DHOD, is a mitochondrial enzyme involved in pyrimidine biosynthesis. The drug selectively affects rapidly dividing cells, such as immune effector cells during inflammation, leading to reductions in interleukin 17 (IL-17) and interferon-gamma production.