Moleculin Biotech has accomplished an end-of-phase 2 assembly with the FDA concerning the investigation of annamycin (MB-106) together with cytarabine for the remedy sufferers with acute myeloid leukemia (AML).1
Throughout the assembly, the corporate and the FDA mentioned outcomes from a section 1b/2 trial (NCT05319587), which is evaluating the mixture in sufferers with newly identified or relapsed/refractory AML.
“The Moleculin staff, together with our regulatory advisors and key opinion leaders, mentioned with FDA the [annamycin] security and efficacy medical findings and proposed subsequent steps for our AML medical improvement program,” Walter Klemp, chairman and chief government officer of Moleculin Biotech, acknowledged in a information launch. “We’re grateful to the FDA for what we think about to be a really productive assembly and stay up for reporting its final result earlier than the top of August.”
Findings from the section 1b/2 trial offered on the 2024 EHA Congress confirmed that efficacy-evaluable sufferers (n = 20) within the intention-to-treat (ITT) inhabitants skilled a composite full remission (CRc) price of 45%, together with a CR price of 40% and a CR with incomplete rely restoration (CRi) price of 5%. Notably, sufferers within the ITT inhabitants had been receiving annamycin plus cytarabine as early as the primary line and as late because the seventh line. Among the many 9 sufferers who achieved a CRc, the median length of response was roughly 7 months and is rising with further follow-up.
Two further sufferers had been enrolled onto the research and handled; nevertheless, their efficacy outcomes are pending.
Sufferers who obtained annamycin plus cytarabine within the second-line setting (n = 10) achieved a CRc price of 60%, together with a CR price of fifty%. Amongst these handled within the first- or second-line settings (n = 13), the CRc and CR charges had been 62% and 54%, respectively.
The continuing, multicenter, open-label section 1b/2 research is enrolling sufferers not less than 18 years of age with pathologically confirmed AML per World Well being Group classification. Sufferers are allowed to be naive to prior remedy or have relapsed/refractory illness after induction remedy. Throughout the dose-expansion portion of the research, sufferers should not allowed to have obtained greater than 2 prior therapies.2
Different key inclusion standards embody sufficient laboratory outcomes and an ECOG efficiency standing of 0 to 2. No chemotherapy, radiation, or main surgical procedure are permitted inside 2 weeks of first research remedy, and any investigational remedy will not be allowed inside 4 weeks of enrollment.
Key exclusion standards include acute promyelocytic leukemia; prior mediastinal radiotherapy; central nervous system involvement; a left ventricular ejection fraction of lower than 50%, valvular coronary heart illness, or extreme hypertension; and any proof of mucositis/stomatitis at enrollment or a historical past of grade 3 or larger mucositis from prior remedy.
All sufferers are handled with intravenous annamycin for 3 consecutive days, adopted by 18 days off remedy, throughout every 21-day cycle. Cytarabine is being administered throughout cycle 1 at 2.0 g/m2 per day for five consecutive days.
The incidence of dose-limiting toxicities and the institution of the utmost tolerated dose and advisable section 2 dose had been the research’s major finish factors. Secondary finish factors included pharmacokinetics and anti-leukemic exercise.
The median age of sufferers within the ITT inhabitants was 69 years. Notably, 89% of sufferers who achieved a CRc had cytogenetics and/or mutations related to poor prognosis, together with FLT3, IDH2, ASXL1, KMT2A and different alterations.3
Security information confirmed that 2 sufferers discontinued remedy early on account of allergic reactions. No clinically vital indicators of cardiotoxicity had been noticed throughout or after remedy in any sufferers. Annamycin plus cytarabine was nicely tolerated, and the most typical adversarial results had been myelosuppression and infections.
The FDA beforehand granted quick monitor and orphan drug designations to annamycin for the remedy of sufferers with relapsed/refractory AML, and the European Medicines Company additionally awarded orphan drug designation to the agent on this indication. The FDA additionally granted orphan drug designation to annamycin for the remedy of sufferers with mushy tissue sarcoma.1
References
- Moleculin completes finish of section 2 assembly with FDA for annamycin in AML. Information launch. Moleculin Biotech. July 10, 2024. Accessed July 15, 2024. https://moleculin.com/moleculin-completes-end-of-phase-2-meeting-with-fda-for-annamycin-in-aml/
- Research of liposomal annamycin together with cytarabine for the remedy of topics with acute myeloid leukemia (AML). ClinicalTrials.gov. Up to date November 18, 2023. Accessed July 15, 2024. https://clinicaltrials.gov/research/NCT05319587
- Moleculin pronounces further constructive preliminary interim information from AML medical trial. Information launch. Moleculin Biotech. June 14, 2024. Accessed July 15, 2024. https://moleculin.com/moleculin-announces-additional-positive-preliminary-interim-data-from-aml-clinical-trial/
