The European Commission ( EC ) has approved Reblozyl ( Luspatercept ) for the treatment of:
a) adult patients with transfusion-dependent anemia due to very low-, low- and intermediate-risk myelodysplastic syndromes ( MDS ) with ring sideroblasts, who had an unsatisfactory response or are ineligible for Erythropoietin-based therapy;
b) adult patients with transfusion-dependent anemia associated with beta thalassemia.
Reblozyl is the first and only erythroid maturation agent approved in the European Union, representing a new class of therapy for eligible patients.
This approval is based on data from the pivotal phase 3 MEDALIST and BELIEVE studies, evaluating the ability of Reblozyl to effectively address anemia associated with MDS and beta thalassemia, respectively.
MEDALIST is a phase 3, randomized, double-blind, placebo-controlled, multi-center study evaluating the safety and efficacy of Reblozyl plus best supportive care ( BSC ) versus placebo plus BSC in adults with IPSS-R-defined very low-, low- or intermediate-risk non-del(5q) MDS.
All patients were RBC transfusion-dependent and were either refractory or intolerant to prior erythropoiesis stimulating agent ( ESA ) therapy, or were ESA naïve and unlikely to respond due to endogenous serum erythropoietin levels of greater than or equal to 200 U/L, and had no prior treatment with disease modifying agents.
The trial showed a statistically significant improvement in RBC transfusion burden with Reblozyl, the study’s primary endpoint, with 37.9% of patients treated with Reblozyl achieving independence from RBC transfusions for at least eight weeks during the first 24 weeks of the trial compared to 13.2% of patients on placebo.
The trial also met the secondary endpoint of transfusion independence for at least 12 weeks within the first 24 and 48 weeks of the study, which was achieved in a significantly greater proportion of patients receiving Reblozyl versus placebo.
The majority of treatment-emergent adverse events ( TEAEs ) were grade 1-2. Grade 3 or 4 TEAEs were reported in 42.5% of patients who received Reblozyl and 44.7% of patients who received placebo.
Discontinuation due to an adverse reaction ( grades 1-4 ) occurred in 4.5% of patients who received Reblozyl.
The most common ( more than 10% ) all-grade adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis and urinary tract infection.
BELIEVE is a phase 3, randomized, double-blind, placebo-controlled multi-center study comparing Reblozyl plus BSC versus placebo plus BSC in adults who require regular RBC transfusions ( 6-20 RBC units per 24 weeks with no transfusion-free period greater than 35 days during that period ) due to beta thalassemia.
The trial showed a statistically significant improvement in RBC transfusion burden during weeks 13 to 24 compared to the baseline 12-week interval prior to randomization ( 21.4% Reblozyl versus 4.5% placebo ), meeting the study’s primary endpoint.
The trial also met the secondary endpoint of transfusion burden reduction of at least 33% ( with a reduction of at least two units ) during weeks 37 to 48, which was achieved in a significantly greater proportion of patients receiving Reblozyl versus placebo.
The trial also met an exploratory endpoint, with 70.5% of patients treated with Reblozyl achieving at least a 33% reduction in RBC transfusion burden of at least two units for any 12 consecutive weeks compared to the 12-week interval prior to treatment, compared to 29.5% of patients on placebo.
The majority of TEAEs were grade 1-2. Discontinuation due to an adverse reaction ( grades 1-4 ) occurred in 5.4% of patients who received Reblozyl.
The most common adverse reactions ( more than 10% ) were headache, bone pain, arthralgia, fatigue, cough, abdominal pain, diarrhea and dizziness. ( Xagena )
Source: BMS, 2020