On July 18, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported additional positive interim safety and efficacy data from its ongoing open label, single arm Phase 1/2 study of Annamycin in Poland (Press release, Moleculin, JUL 18, 2019, View Source [SID1234537617]). Three patients were treated at dose level of 150 mg/m2 with no drug-related adverse events, including no signs of cardiotoxicity. The results for all 3 patients were reviewed by the Drug Safety Review Committee, which determined that the trial could progress to the next higher dose level of 180 mg/m2. To date in Poland, one patient experienced grade 2 mucositis (which resolved to grade 1 within 2 days) and no other adverse events related to Annamycin have been reported. One patient has completed treatment in the 120 mg/m2 (second) cohort in the Company’s parallel US clinical trial (the US trial started at a lower initial dose of 100 mg/m2).
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"Recruitment in Poland continues to move rapidly," commented Walter Klemp, Moleculin’s Chairman and CEO. "And, moving beyond the 150 mg/m2 dosing level is quite significant, as the prior developer of Annamycin was unable to dose beyond this level. We remain optimistic that new methods for reducing the onset of mucositis (the dose limiting toxicity for Annamycin in prior clinical trials) will allow us to safely increase dosing to 180 mg/m2 or potentially even higher."
Mr. Klemp continued: "It’s also important to remind people that one of the advantages we believe Annamycin will offer is a lack of cardiotoxicity. We continue to see no evidence of cardiotoxicity in any of the patients treated thus far. We intend to advance the clinical study of Annamycin with the goal of ultimately demonstrating the drug’s safety and effectiveness to support regulatory approval in both the US and European Union."
Study Design
The Company is studying Annamycin in both the US and Poland in open label, single arm clinical trials to assess the safety and efficacy of Annamycin for the treatment of adults with relapsed or refractory acute myeloid leukemia. Both the US and Polish trials have the same study design, providing for a Phase 1 intended to establish a "Recommended Phase 2 Dose," ("RP2D") with cohorts of 3 patients each where the first cohort starts at a low beginning dose and each successive cohort receives the next higher dose level until "dose limiting toxicities" prevent further increases. In the case of cohort 1 in the US, one patient did not complete the evaluation protocol, so a fourth patient was added to complete that cohort.
A key difference in the US is that the starting dose was 100 mg/m2, whereas, in Poland, the starting dose was 120 mg/m2. Having completed the first cohort in the US, the Company is seeking patients for the second cohort at a dose level of 120 mg/m2 and 1 of the 3 patients required to fill the cohort has now been treated. Now that 3 patients have completed the safety evaluation period of the second cohort in Poland,
the third cohort will begin there at a dose level of 180 mg/m2. Once the Company establishes an RP2D, the intent is for each trial to advance to a Phase 2 arm planned to assess the safety and efficacy of Annamycin in 21 additional patients.
The US trial also differs from the Polish trial in that the FDA would like to review safety data relating to cardiotoxicity from patients treated prior to advancing beyond 120 mg/m2. The Company believes that the additional patient safety data gained from the Polish trial will assist in the FDA’s review of cardiac safety.