Imara’s tovinontrine has reached the end of the line in sickle cell and beta thalassemia. With the phase 2b trials failing despite a midstudy endpoint change and the use of a higher dose, Imara has called time on its work to establish tovinontrine in the diseases, triggering more damage to its battered stock price.
Expectations for the PDE9 inhibitor plummeted in January 2021 when a phase 2a sickle cell trial found fetal hemoglobin actually fell numerically from baseline to Week 24. Imara went on to change the primary endpoint of its phase 2b Ardent trial in sickle cell disease, switching to vaso-occlusive crises after linking the drug to a 25% fall in the rate of the painful complication in its phase 2a trial. And, with Ardent testing a higher dose than the phase 2a, Imara held out hope going into the interim analysis.
That hope was swiftly extinguished by the data. At the higher dose, tovinontrine was no better than the placebo at reducing the median annualized rate of vaso-occlusive crises, causing the trial to miss its primary endpoint.
Imara switched to that primary endpoint late last year. The change made no difference on the outcome, with tovinontrine also failing to beat placebo against the original primary fetal hemoglobin endpoint.
The Boston-based biotech disclosed the Ardent results alongside the interim analysis of its phase 2b trial in beta thalassemia. In transfusion-dependent patients, tovinontrine provided no meaningful benefit in transfusion burden over placebo. Similarly, the drug candidate failed to trigger improvements in total hemoglobin and other disease-related biomarkers in non-transfusion-dependent patients.
Imara has seen enough. With both studies failing, the biotech plans to stop the studies in the second quarter as part of the discontinuation of the development of tovinontrine in the indications. However, Imara is yet to give up completely on the candidate.
“Moving forward, we plan to consider our strategic options, including development of tovinontrine in heart failure with preserved ejection fraction as well IMR-261 clinical development plans,” Imara CEO Rahul Ballal said in a statement. Both those development opportunities are still in preclinical.
Shares in Imara fell more than 30% in premarket trading, dragging the stock down to around $1. Imara ended 2021 with $90 million, a sum it predicted would see it through to the first quarter of next year.