An Imara drug targeting a new target for the treatment of a rare inherited hemoglobin disorder has failed two interim studies, one in sickle cell disease and the other in beta thalassemia. The biotech company said Tuesday that it would halt both projects.
In preliminary results, Imara said its drug, tovinontrine, failed to distance itself from a placebo in any of the clinical trials. The small molecule is also being developed as a potential treatment for heart failure. Given the disappointing data from the blood disease study, Boston-based Imara said it was weighing its options for the program against IMR-261, a drug candidate that offers an alternative to treating hemoglobin disorders.
“Going forward, we plan to consider our strategic options, including the development of tovinontrine for heart failure with preserved ejection fraction (HFpEF) and the IMR-261 clinical development program,” Imara President and CEO Rahul Ballal said in a prepared statement said in the statement.
Tovinontrine is a small molecule designed to target and block an enzyme called phosphodiesterase 9 (PDE9). This enzyme selectively degrades signaling molecules that play a role in vascular biology. By blocking PDE9, Imara’s drug aims to boost levels of this key signaling molecule. Tovinontrine is expected to lead to higher levels of fetal hemoglobin, thereby reducing red blood cell sickling characteristic of sickle cell disease. This approach has also been tested in beta thalassemia, a disorder that causes low levels of hemoglobin.
The primary goal of the Phase 2b sickle cell study is to measure the annualized rate of vaso-occlusive crisis, the amount of time sickle red blood cells block blood flow and deprive tissues of oxygen. According to preliminary results released Tuesday, the reduction in the incidence of these crises was not sufficient to be statistically significant in patients who received tovinontrine compared to the placebo group.
In beta thalassemia, the primary study objective is to evaluate the safety and tolerability of the drug in patients who are transfusion-dependent and transfusion-independent for the disease. For those who rely on blood transfusions, the study also assessed the drug’s ability to reduce the burden of blood transfusions. In the low- and high-dose tovernontriline tested in the beta thalassemia study, Imara reported that “no meaningful benefit was observed in terms of transfusion burden.”
One bright spot for Tovinontrine was that the drug was well tolerated by patients and showed no safety issues that could hinder testing in other indications. January, the FDA approves Imara’s application Human testing of tovernontriline in heart failure with preserved ejection fraction begins.last month, in its Fourth Quarter and Full Year 2021 Financial Results ReportImara said it expects to dose the first patient in a Phase 2 study in the heart failure indication in the second quarter of this year.
Imara has another opportunity to address hemoglobin disorders. Last October, the company acquired a compound called CXA-10 from Complexa, a Berwyn, Pa.-based biotech that has been shown to be active in the rare kidney disease focal segmental glomerulosclerosis and pulmonary hypertension. taking the test. The small molecule, now renamed IMR-261, is designed to activate a transcription factor called Nrf2. Imara has said the approach has the potential to increase fetal hemoglobin and potentially provide a treatment for hemoglobin disorders and iron disorders.
Image: Meletios Verras, Getty Images
