Announcement • Jun 30
Moleculin Biotech Reports Positive Interim Results from Phase 2/3 Miracle Trial of Annamycin in Relapsed or Refractory Acute Myeloid Leukemia
Moleculin Biotech, Inc. announced positive preliminary unblinded efficacy results from the first 45 patients enrolled in Part A of the Company's pivotal Phase 2/3 MIRACLE trial, analyzed on a full intent-to-treat basis with no patient exclusions. Both Annamycin treatment arms demonstrated favorable efficacy trends compared with the control arm in patients with relapsed or refractory acute myeloid leukemia (R/R AML). The interim analysis demonstrated a clear efficacy advantage for both Annamycin treatment arms, 190 mg/m² plus HiDAC and 230 mg/m² plus HiDAC, over the HiDAC control arm. CR reached 43% and 36% in the respective Annamycin cohorts, compared with 12% for control, while CRc reached 50% and 57%, respectively, versus 29% for the control arm. The n=45 population contained 75.6% over 60 years of age, 55.6% 7+3 and 31.1% venetoclax regimens for first line (1L) therapies. The remission rates for all three arms, including the control arm, reflect outcomes measured after only a single cycle of therapy, as specified by the MIRACLE protocol. The most commonly cited historical benchmarks in this setting, including the MIRROS and CLASSIC I studies, as well as Moleculin’s own MB-106 study, permitted multiple cycles of treatment. The Company therefore expected absolute remission rates for both the control and Annamycin arms in this single-cycle interim analysis to be lower than those reported in such multi-cycle datasets and believes the most meaningful comparison is the performance of the Annamycin arms relative to the concurrent, randomized control arm evaluated on the same single-cycle basis. The interim review was conducted by the trial's Independent Data Monitoring Committee (iDMC). The committee unanimously concluded that for the primary efficacy endpoint of CR rates, although there was no statistical significance, there was a strong numeric trend suggesting that the experimental treatment arms (L-Annamycin at one of two doses plus high dose cytarabine) were superior to the placebo plus high dose cytarabine control arm. To that end, there was sufficient evidence of efficacy to support continuing the trial. The committee also concluded that the data did not support dropping either of the two experimental treatment arms since the efficacy data were too similar between these two treatment arms. The Company decided to accept the recommendation of the iDMC and continue with the MIRACLE trial as planned. The absence of formal statistical significance at this first interim analysis reflects the trial’s prespecified statistical design, not the strength of the data. As in most group-sequential studies, MIRACLE distributes its statistical “budget” across three planned analyses using a conservative O’Brien-Fleming spending function, which by design sets a very high bar for significance at an early interim look and reserves essentially the entire budget for the final analysis in the full population of approximately 282 subjects. Statistical significance was therefore neither expected nor required at this stage; the relevant question at an interim look is the direction and strength of the efficacy trend, which the iDMC found clearly favored both Annamycin arms over control. The trial remains fully powered, at 80%, to establish statistical significance at its planned final analysis (calculated to detect 20% vs. 35% CR for control vs. test, respectively). The MIRACLE trial is a pivotal Phase 2/3, multi-center, randomized, double-blind, placebo-controlled, adaptive design study of L-Annamycin for injection in combination with Cytarabine injection versus placebo in combination with Cytarabine injection as second line therapy for remission induction in adult subjects with R/R AML. Part A of the study is designed to identify the optimal Annamycin dose before advancing into the pivotal portion of the trial. Moleculin reported that 67 of the targeted 90 patients for Part A have been enrolled, representing approximately 74% of the planned enrollment. Following completion of Part A, the selected dose arm is expected to advance into Part B, where efficacy data from Part A will be carried forward into the pivotal analysis. Acute myeloid leukemia remains an area of significant unmet medical need, particularly among patients who relapse after frontline therapy. Moleculin believes the preliminary MIRACLE results further support Annamycin's potential to improve remission outcomes in this patient population and strengthen the rationale for the program's continued advancement toward registration. The interim results related to efficacy are final and other data remain subject to Part A final database review and readout.
