FDA Waives ODAC Review of Luspatercept in MDS

The FDA’s Oncologic Drugs Advisory Committee will not be reviewing an sBLA for luspatercept-aamt for use as a treatment for patients with myelodysplastic syndromes.

The FDA’s Oncologic Drugs Advisory Committee (ODAC) meeting on December 18, 2019, will no longer include a session reviewing a supplemental Biologics License Application (sBLA) for luspatercept-aamt (Reblozyl) for use as a treatment for patients with myelodysplastic syndromes (MDS), according to Bristol-Myers Squibb and Acceleron Pharma, the codevelopers of the erythroid maturation agent.1

The companies noted in a press release that the FDA action date for a final decision on the sBLA remains April 4, 2020. The sBLA for luspatercept is specifically for patients with very low- to intermediate-risk MDS-associated anemia who have ring sideroblasts and require red blood cell (RBC) transfusions.

ODAC panel meetings typically produce recommendations on applications for which there is some uncertainty regarding the benefit-risk profile for the treatment. The FDA is not required to follow the recommendation of the panel.

The sBLA for luspatercept is based on the international, multicenter, phase III MEDALIST trial.2 In the study, the efficacy and safety of luspatercept was compared with placebo in patients aged ≥18 years who had anemia due to MDS defined as very low-, low-, or intermediate-risk according to the Revised International Prognostic Scoring System. Patients who were eligible also had ring sideroblasts ≥15% or ≥5% with an SF3B1 mutation, required ≥2 RBC transfusions every 2 months, bone marrow blasts <5%, and were refractory to, intolerant of, or ineligible for erythropoiesis-stimulating agents (ESAs).

There were 229 patients randomized 2:1 to receive either subcutaneous luspatercept at a starting dose level of 1 mg/kg every 3 weeks, with titration up to 1.75 mg/kg, if needed (n = 153), or placebo subcutaneously every 3 weeks (n = 76) for ≥24 weeks.

MDS disease was assessed after 24 weeks and every 6 months thereafter until treatment was discontinued or patients had disease progression. Patients were followed for ≥3 years after their last dose for acute myeloid leukemia progression, and subsequent MDS treatment and survival.

The primary endpoint was RBC-TI for ≥8 weeks between week 1 and week 24; secondary endpoints included RBC-TI for ≥12 weeks between week 1 and 24, and between week 1 and 48. Moreover, achievement of modified hematologic improvement-erythroid (mHI-E) response for any consecutive 56-day period was assessed using International Working Group 2006 criteria.

The median age was 71 years (range, 26-95). Patients were a median 41.8 months (range, 3-421) from diagnosis, and the majority were male (62.9%). They received a median 5 RBC units (range, 1-20) transfused over 8 weeks during the 16 weeks prior to treatment, including 43.2% who had ≥6 RBC units/8 weeks, 27.9% who had ≥4 to <6 RBC units/8 weeks, and 28.8% who had <4 RBC units/8 weeks.

At baseline, 60.3% of patients had serum erythropoietin levels <200 IU/L, 25.3% with levels 200 to 500 IU/L, and 14% with levels >500 IU/L. In total, 218 patients (95.2%) previously received ESAs, and 206 (90.0%) tested positive for an SF3B1 mutation.

Findings demonstrated that 37.9% of patients treated with luspatercept experienced RBC transfusion independence (RBC-TI) for ≥8 weeks versus 13.2% in those who received placebo (odds ratio [OR], 5.1; P <.0001).2

Moreover, 52.9% of patients treated with luspatercept achieved an mHI-E response versus 11.8% of those who received placebo (P <.0001), and 28.1% of patients on the luspatercept arm achieved RBC-TI for ≥12 weeks versus 7.9% of the placebo group (OR, 5.1; P = .0002). Safety findings were consistent with prior data of luspatercept; there were 3 treatment-related grade 3 adverse events (AEs) that included myalgia, increased blast cell count, and general physical health deterioration.

The FDA approved luspatercept in November 2019 for the treatment of anemia in adult patients with beta thalassemia who require regular RBC transfusions.


  1. Bristol-Myers Squibb and Acceleron Pharma Provide Update on FDA Advisory Committee for Reblozyl® (luspatercept-aamt). BMS. Published December 6, 2019. https://bit.ly/34SCgEh. Accessed December 6, 2019.
  2. Fenaux P, Platzbecker U, Mufti GJ, et al. The MEDALIST Trial: results of a phase 3, randomized, double-blind, placebo-controlled study of luspatercept to treat anemia in patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts (RS) who require red blood cell (RBC) transfusion. Blood. 2018;132:1. doi: 10.1182/blood-2018-99-110805.