Imara unveiled data from two subgroups of a Phase IIa trial for its lead compound Wednesday, aiming to conjure up a positive light despite challenges tied to the Covid-19 pandemic. But investors weren’t buying it and sent the company’s shares into a tailspin.
The experimental drug, dubbed IMR-687, is being evaluated for sickle cell disease as both a monotherapy and in combination with hydroxyurea. In the monotherapy subgroup, Imara reported IMR-687 showed no meaningful changes in F-cells, fetal hemoglobin (HbF) levels or Hb levels from baseline after 24 weeks.
Additionally, in the combo subgroup, the candidate demonstrated numerical increases in F-cells and HbF levels from baseline, but Hb levels did not meaningfully change. But Imara was unable to measure the difference against a placebo in both groups, as patients in those arms could not be evaluated due “in part” to missed study visits, the company said.
Ultimately, only one placebo patient in the combination group had appropriate biomarker data after the 24-week period, and p-values were not reported. Imara attempted to spin those less-than-stellar results into a win in a release, but investors saw through the effort immediately.
“I am encouraged by the incremental data from this readout, especially in light of the COVID-19 pandemic challenges,” lead investigator Biree Andemariam said in a statement. “This includes a favorable safety profile of IMR-687, lower rate of VOCs/SCPCs and VOC-related hospitalizations in the Population A1 monotherapy arm and improvements in several biomarker results across both the monotherapy and combination groups.”
Imara $IMRA shares were down 33% in early trading Wednesday.
The results make up part of a 93-patient Phase IIa trial, studying four different dose levels across the monotherapy and combination regimens. Wednesday’s monotherapy data come from a regimen of a once-daily dose of 100 mg through 4 weeks, which escalates to 200 mg through an additional 20 weeks.
In the combination group, patients took a 50 mg dose once a day on top of standard of care HU, with escalation after 4 weeks to 100 mg for the remaining 20 weeks. There were 18 total individuals in this monotherapy cohort and 14 in the combo portion.
Imara can still hang its hat on interim data from the other subgroups in the study, which showed the higher dose of the monotherapy had statistically significant increases in F-cells, as well as a dose-dependent increase in HbF levels in adults. There was also a mean increase from baseline of 1.7% in HbF percentage in the 100 mg / 200 mg dose group through week 24, a figure that SVB Leerink analyst Joseph Schwartz had deemed promising.
Ahead of Wednesday’s data, Schwartz had been hoping to see a further rise in this specific data point, regardless of whether or not it reached the 3% level the FDA set as the threshold for the Phase IIb study that launched in August. But the overall percent change in monotherapy reported Wednesday was -1.1%, even though Imara noted an absolute, dose-dependent increase in HbF of 1.3% when patients escalated from 100 mg to 200 mg.
Schwartz wrote Wednesday that he does not believe the data is a good indicator of the upcoming Phase IIb results, and still believes the 3% figure is achievable. He also noted that the doses being used in that study are much higher — up to 400 mg — than those in Phase IIa, with signs pointing to longer and higher doses resulting in better efficacy.
IMR-687 was one of a group of small molecule PDE9 inhibitors that Imara had licensed from Lundbeck. The theory is that blocking PDE9 increases cyclic GMP levels, which is associated with reactivation of fetal hemoglobin and thus restore some functionality impaired in blood disorders. Imara went public in March following a $75.2 million IPO raise.
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