FDA Accepts sBLA of Luspatercept for Anemia in Patients With Lower-Risk MDS

The FDA has accepted the supplemental biologics license application (sBLA) and the EMA has validated the type II variation application for luspatercept-aamt (Reblozyl) for the treatment of anemia without prior use of erythropoiesis-stimulating agents in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require red blood cell (RBC) transfusions.¹

The FDA has granted the application priority review and set the Prescription Drug User Fee Act (PDUFA) goal date to August 28, 2023. The validation of the application from the EMA also confirms that the submission is complete, and the centralized review process will commence.

These applications come from findings from the phase 3 COMMANDS study (NCT03682536) which evaluated first-in-class luspatercept. Data showed that treatment with luspatercept led to highly statistically significant and clinically meaningful improvements in RBC transfusion independence for ≥12 weeks with concurrent hemoglobin increase (≥1.5 g/dL) vs treatment with an erythropoiesis-stimulating agent among patients with very low/low/intermediate-risk MDS.

“Initial treatment options for very low- to intermediate-risk myelodysplastic syndromes, including erythropoiesis-stimulating agents, can alleviate anemia in some patients but others will either not respond or become resistant to therapy, and additional therapy options have remained urgently needed,” said Noah Berkowitz, MD, PhD, senior vice president, Hematology Development, Bristol Myers Squibb, in the press release. “Results from the COMMANDS study showed [luspatercept] significantly improved transfusion independence and elevated hemoglobin compared to ESA therapy epoetin alfa. [Luspatercept] is an important option available for the treatment of anemia in patients with transfusion-dependent, lower-risk MDS who have experienced ESA failure, and we look forward to working with the FDA and EMA to expand its potential use as a first-line therapy in eligible patients.”

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Luspatercept is a first-in-class erythroid maturation agent which enhances late-stage erythropoiesis that has indications for the treatment of patients with lower-risk myelodysplastic syndrome (LR-MDS) by the FDA and EMA.

In the phase 3, open-label, randomized COMMANDS study, investigators evaluated the efficacy and safety of luspatercept compared with epoetin alfa for the treatment of patients with anemia due to very low-, low- or intermediate-risk MDS who are RBC transfusion dependent and were erythropoiesis stimulating agent naïve.²

Enrollment in the study was open to adult patients who had a documented diagnosis of MDS, very low, low, or intermediate risk disease according to WHO 2016 classification, < 5% blasts in bone marrow, an endogenous serum erythropoietin level of < 500 U/L, and an ECOG performance status of 0, 1, or 2. Patients must have also had RBC transfusions which consisted of an average transfusion requirement of 2 - 6 units/8 weeks of packed red blood cells confirmed for a minimum of 8 weeks immediately preceding randomization.

Investigators assessed the primary end point of RBC transfusion independence for 12 weeks with a mean hemoglobin increase ≥ 1.5 g/dL and secondary end points of RBC transfusion independence for 24 weeks, RBC transfusion independence ≥12 weeks, and erythroid response of at least 8 weeks during weeks 1-24 of the study.

Other end points explored in the study were mean hemoglobin change over 24 weeks, hematologic improvement, time to first RBC transfusion, RBC transfusion burden on treatment, safety, pharmacokinetics, frequency of antidrug antibodies, number and percentage of participants progressing to acute myeloid leukemia (AML), time to AML progression, and overall survival.

Full results from the COMMANDS trial are expected to be presented at upcoming medical meetings.¹

REFERENCES:

U.S. FDA accepts for priority review supplemental biologics license application and EMA validates application for Reblozyl® (luspatercept-aamt) as first-line treatment of anemia in adults with lower-risk myelodysplastic syndromes (MDS). News release. Bristol Myers Squibb. May 1, 2023. Accessed May 1, 2023. https://bit.ly/3HuiOTI

A study to compare the efficacy and safety of luspatercept (ACE-536) versus epoetin alfa for the treatment of anemia due to IPSS-R very low, low, or intermediate risk myelodysplastic syndromes (MDS) participants who require red blood cell transfusions and are ESA naïve (COMMANDS). ClinicalTrials.gov. Updated April 18, 2023. Accessed May 1, 2023. https://clinicaltrials.gov/ct2/show/NCT03682536