FDA Grants Priority Review to Luspatercept for First-line Treatment of Anemia in Lower-risk MDS

FDA seeks to expand current indication for luspatercept-aamt (Reblozyl) to include treatment of anemia in patients with very low- to intermediate-risk myelodysplastic syndrome (MDS) with additional organisms granted priority review to the Pharmaceutical Product License Application (sBLA). Persons who have not previously received an erythropoiesis stimulating agent (ESA) and who may require a red blood cell (RBC) transfusion.¹

In addition, the European Medicines Agency (EMA) validated a Type II variation application for luspatercept in the same indication.

This submission was supported by data from the Phase 3 COMMANDS trial (NCT03682536). This study showed that Ruspatercept demonstrated statistically significant and clinically meaningful improvement over epoetin alfa in RBC transfusion independence over 12 weeks, increasing concurrent hemoglobin by at least 1.5 g. it was done. /dL in her MDS patients with very low, low, or intermediate risk requiring RBC transfusion.

Detailed findings from COMMANDS will be presented at an upcoming medical conference.

FDA has assigned a target action date of August 28, 2023, based on the Prescription Drug Fee Act. The EMA will also initiate a centralized review process after validating the application.

“Initial Treatment Options [patients with] Very low- to moderate-risk MDS, including ESAs, can alleviate anemia in some patients, while others do not respond or become refractory to treatment, and additional treatment options are available. is urgently needed. , Hematology Development, Bristol-Myers Squibb, said in a news release. “The results of the COMMANDS study [luspatercept] Transfusion independence was greatly improved and hemoglobin was elevated. [with the] ESA therapy, epoetin alfa. [Luspatercept] is an important option for the treatment of anemia in patients with transfusion-dependent low-risk MDS who have experienced ESA failure, and we are working with the FDA and EMA to expand its potential use as a first-line therapy. looking forward to Eligible Patients. ”

In November 2019, FDA Luspatercept for the treatment of anemia in adult patients with beta-thalassemia Those who require regular red blood cell transfusions.² Additionally, in April 2020, the FDA approved the drug as a Treatment of ESA failure anemia In adult patients with very low to moderate risk MDS with ringed sideroblasts or myelodysplastic/myeloproliferative neoplasms with ringed sideroblasts and thrombocytosis, 2 or more RBC units over 8 weeks is required.³

In the open-label, randomized COMMANDS study, MDS were evaluated according to the International Prognostic Scoring System (IPSS-R) classification of very low-risk, low-risk, or intermediate-risk disease as revised at the World Health Organization’s 2016 Classification Conference. Patients with a documented diagnosis of Key inclusion criteria included less than 5% myeloblasts, an endogenous serum erythropoietin level less than 500 u/L, and an ECOG performance status of 0–2. A requirement of 2–6 units every 8 weeks of packed RBCs was confirmed for a minimum of 8 weeks immediately prior to randomization.

Patients with clinically significant anemia due to iron, vitamin B12, or folate deficiency were excluded. autoimmune or hereditary hemolytic anemia; hypothyroidism; or any type of known clinically significant bleeding or sequestration or drug-induced anemia. Other key exclusion criteria included known history of acute myeloid leukemia or uncontrolled hypertension.

The study enrolled 363 patients who were randomized to receive either luspatercept or epoetin alfa.

Twelve-week RBC transfusion independence with a mean hemoglobin increase of at least 1.5 g/dL served as the primary endpoint of the study. Key secondary endpoints included RBC transfusion independence at 24 weeks and RBC transfusion independence for at least 12 weeks and red blood cell response for at least 8 weeks between weeks 1-24.

In terms of safety, the findings from COMMANDS were reported to be consistent with the toxicity profile of luspatercept observed in previous clinical trials and post-marketing settings.

References

1. The U.S. FDA accepted a priority review add-on biologics application, and the EMA approved a submission for Reblozyl (luspatercept-aamt) for the first-line treatment of anemia in adults with low-risk myelodysplastic syndrome (MDS). news release. Bristol-Myers Squibb. May 1, 2023. Accessed May 1, 2023. https://news.bms.com/news/details/2023/
2. FDA approves luspatercept-aamt for anemia in patients with beta-thalassemia. FDA. November 8, 2019. Accessed May 1, 2023.
3. FDA approves luspatercept-aamt for anemia in adults with MDS. FDA. April 3, 2020. Accessed May 1, 2023.
4. Luspatercept (ACE-536) and epoetin alfa for the treatment of anemia with IPSS-R in very low-risk, low-risk, or intermediate-risk myelodysplastic syndrome (MDS) participants requiring red blood cell transfusions. Studies comparing efficacy and safety. ESA naive (command). ClinicalTrials.gov. Updated April 18, 2023. Accessed May 1, 2023. https://clinicaltrials.gov/ct2/show/NCT03682536