Immunic's lead drug fails to impress in 2 separate trials — and it's blaming some of its woes on the pandemic
The pandemic has posed a serious challenge to the way drugmakers do business, which has made it an easy scapegoat for clinical trial duds. Once looking to solve Covid-19, Immunic’s lead drug has now flopped one study and failed to impress in another — is it fair to blame the pandemic for that?
On Wednesday, the biotech revealed a study for its lead program in Covid-19 could not be evaluated for its primary and secondary endpoints. Then on Thursday, Immunic said the same program hit statistical significance in primary sclerosing cholangitis — though only barely — while noting the study population ended up much smaller than expected because of pandemic restrictions.
The Covid-19 news from Wednesday sent Immunic $IMUX shares down about 20%, while Thursday’s PSC update left a more muted impression on Wall Street: in early morning trading, the company stock was flat.
The Immunic program in question is an oral treatment called IMU-838, which aims to block the enzyme dihydroorotate dehydrogenase, or DHODH, and inhibit the intracellular metabolism of activated T and B cells. DHODH inhibitors can also produce a host-based antiviral effect regardless of specific virus proteins and structure, and Immunic is hopeful this can lead to use as the treatment of several different viruses.
Immunic largely pinned the Covid-19 trial miss on the way the treatment landscape has changed throughout the pandemic. Researchers launched the study almost a year ago — back in March, to be exact — when there was nearly zero scientific consensus on how to treat the disease.
As a result, Immunic went after ventilation in moderate Covid-19 cases. They sought to measure how well its program could reduce the need for invasive ventilation after four weeks in moderate cases. But over the course of the study, they found that less than 1% of hospitalized Covid-19 patients with moderate cases needed ventilators at all, essentially preventing them from measuring how effective their program is in this population.
Similar miscalculations occurred in the secondaries as well. Going for 28-day mortality, survival without respiratory failure and reducing ICU admissions in moderate cases, Immunic again found incidence rates that were too low to conduct analyses. Their study found mortality to be under 2% and less than 4.5% of patients required an ICU stay.
Given how little was known about the novel coronavirus at the outset of the pandemic, it’s certainly possible that Immunic is far from the only biotech to shoot for these aggressive endpoints and come up short. But they tried to pull a positive out of the data, highlighting that the program showed a numeric advantage in time to recovery over placebo: in patients who were 90% likely to recover from Covid-19, those taking IMU-838 felt better after 18.9 days as opposed to the 26.8 days needed in the placebo arm.
Immunic also presented data that the therapy could be helpful against “long Covid,” where patients who have successfully flushed the virus from their systems continue to suffer from symptoms and an overactive immune system, sometimes for months. A post-hoc analysis of 27 patients saw lower numeric levels of long Covid-related fatigue in the drug arm.
CEO Daniel Vitt said in a conference call Thursday morning that the company expects to speak with regulators about how to proceed in Covid-19 and can hopefully plan a Phase III trial, but isn’t sure what that trial might look like yet.
The pandemic also affected the program’s study in PSC, as much of the treatments were administered at the Mayo Clinic in Minnesota. Patients had to travel to the site, which sometimes proved challenging over the last several months, Vitt said. Originally planning to enroll 30 patients, Immunic ended up only being able to administer the experimental drug to 18 patients while only 11 finished the 24-week treatment course. And in late 2020 the principal investigator determined the trial needed to be stopped.
Looking to reduce serum ALP in adults with PSC after 24 weeks, researchers found IMU-838 decreased levels by an average of 5.76 IU/L every 30 days in these 11 patients. That was good for a p-value of p=0.041, hitting statistical significance but coming close to the p=0.05 border.
The program did not hit statistical significance in the 18-patient population that included those who didn’t finish the study, registering an average baseline change of -2.11 and hitting a p-value of 0.578. Both studies found the candidate to be safe and well-tolerated, and Immunic is planning to move forward with another trial in PSC as well.
In addition to Covid-19 and PSC, the candidate is also being studied to treat multiple sclerosis, ulcerative colitis and Crohn’s disease. Last August, the company released topline data in relapsing-remitting MS patients, saying the experimental drug reduced the cumulative number of combined unique active MRI lesions after 24 weeks compared to placebo.