Additional positive interim safety and efficacy data from 2 ongoing open label, single arm phase I/II studies of annamycin for the treatment of relapsed or refractory acute myeloid leukemia (AML) were reported, according to Moleculin Biotech, the agent’s manufacturer.
In the latest cohort in Poland, 1 of 3 patients treated with a single dose (180 mg/m2) in phase I had a partial response sufficient to qualify for a potentially curative bone marrow transplant. The results for all 3 patients, reviewed by the Safety Review Committee, were determined to have no drug-related adverse events (AEs) that would prevent advancing the trial. This brings the total number of patients treated and evaluated at or above 120 mg/m2 to 10.
“Although it is still early and the data are preliminary, I believe we may see that annamycin has significant activity against relapsed and refractory AML. To have a 40% response rate this early in the dose-escalating process is very encouraging. And if the product ultimately is shown to have little or no cardiotoxicity – as the preliminary data suggest – there is a real potential for Annamycin to become the first approved anthracycline without a dose-limiting cardiovascular risk,” Robert Shepard, MD, Moleculin’s Chief Medical Officer for Annamycin, said in a press release.
Phase I was designed to establish the safety of Annamycin and to determine the recommended dose to be used in phase II. The primary endpoint of phase I was safety, and the secondary endpoint was the assessment of efficacy generally defined as an improvement in bone marrow biopsy results sufficient to qualify patients for a potentially curative bone marrow transplant.
Cohorts 1, 2, and 3 in Poland received a dose of 120 mg/m2, 150 mg/m2, and 180 mg/m2 respectively, and results now permit moving to the next higher dose level of 210 mg/m2. In the U.S. trial, cohort 1 started at 100 mg/m2 and only 1 patient has completed treatment in the second cohort at 120 mg/m2.
The interim results for the 10 patients showed 1 complete response with incomplete recovery (CRi) of white blood cells and/or platelets, and 2 partial responses (PR) where bone marrow blasts were reduced 50% and to below 25%. One additional patient was bridged to bone marrow transplant based on a sufficient reduction in bone marrow blasts, bringing the total to 4 out of 10 who have demonstrated efficacy at or above 120 mg/m2.
In the European trial, only 1 AE related to annamycin has been reported thus far; a patient experienced grade 2 mucositis, which resolved to grade 1 within 2 days. In the parallel U.S. trial, the first patient of cohort 2 achieved a “morphologically leukemia free state,” which also constitutes a CRi, after receiving a single dose of 120 mg/m2.
Moreover, of the 14 patients treated thus far in both trials, none have shown any evidence of cardiotoxity; including 7 patients in Poland who were treated at levels above the U.S. maximum allowable cumulative anthracycline dose level (550 mg/m2).
“If upheld in further studies, this lack of toxicity could be an important differentiator between annamycin and the currently approved anthracyclines, for which cardiotoxicity is a well-known treatment limitation,” the company wrote in a press release.
Currently there are only 2 clinical trials, including Moleculin Biotech’s, that are studying Annamycin. The second study, conducted by Callisto Pharmaceuticals, is being carried out in patients with refractory or relapsed acute lymphocytic leukemia to identify the maximum tolerated dose and evaluate the safety of the agent.
Moleculin Announces Additional Positive Interim Results from Phase I/2 Clinical Studies of Annamycin in Acute Myeloid Leukemia [news release]. Houston, Texas. Published December 4, 2019. ir.moleculin.com/press-releases/detail/148/moleculin-announces-additional-positive-interim-results. Accessed December 4, 2019.