Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ: XLRN) today announced results from the pivotal, phase 3 MEDALIST trial evaluating the efficacy and safety of investigational luspatercept to treat patients with ring sideroblast (RS+) myelodysplastic syndromes (MDS)-associated anemia who require red blood cell transfusions and who had failed, were intolerant to, or ineligible for erythropoietin therapy. Results were presented by Alan F. List, M.D. during the Plenary Scientific Session at the 60th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, C.A. (Abstract #1).
“Severe anemia resulting in red blood cell transfusion dependence is a significant challenge for patients with low- and intermediate-risk MDS. Those who become resistant or refractory to currently available treatments have limited alternatives,” said Dr. List, President and CEO of Moffitt Cancer Center. “The findings from MEDALIST are very exciting as they support the hypothesis that targeting red blood cell precursor maturation could help to address patients’ anemia and allow them to achieve transfusion independence.”
MEDALIST met the primary endpoint of red blood cell transfusion independence (RBC-TI) for 8 or more weeks during the first 24 weeks of the study. Treatment with luspatercept resulted in a statistically significantly greater proportion of patients achieving RBC-TI ≥ 8 weeks compared to placebo. The study also found in secondary endpoints that treatment with luspatercept resulted in a statistically significant higher percentage of patients achieving RBC-TI of 12 or more weeks in the first 24 or 48 weeks of the study, as well as hematologic improvement-erythroid (HI-E) of 8 or more weeks.
Endpoints Luspatercept Placebo P-Value
RBC-TI ≥8 weeks (weeks 1-24) 37.9 % (58/153) 13.2 % (10/76) < 0.0001
RBC-TI ≥12 weeks (weeks 1-24) 28.1 % (43/153) 7.9 % (6/76) 0.0002
RBC-TI ≥12 weeks (weeks 1-48) 33.3 % (51/153) 11.8 % (9/76) 0.0003
HI-E ≥ 8 weeks (IWG 2006, weeks 1-24) 52.9 % (81/153) 11.8 % (9/76) < 0.0001
MEDALIST Safety Summary
Treatment-emergent adverse events (TEAEs) of Grade 3 or 4 were reported in 42.5% (65/153) of patients receiving luspatercept and 44.7% (34/76) of patients receiving placebo. Progression to acute myeloid leukemia (AML) occurred in four patients, three patients (2.0%) receiving luspatercept and one patient (1.3%) receiving placebo. Five patients receiving luspatercept (3.3%) and four patients receiving placebo (5.3%) experienced one or more TEAE that resulted in death.
Most common TEAEs of any Grade in Greater than 10% of Patients in Either Arm
Fatigue 26.8 % 13.2 %
Diarrhea 22.2 % 9.2 %
Asthenia 20.3 % 11.8 %
Nausea 20.3 % 7.9 %
Dizziness 19.6 % 5.3 %
Back pain 19.0 % 6.6 %
“The MEDALIST results demonstrate the potential clinical benefit of luspatercept in achieving red blood cell transfusion independence in patients with low-to-intermediate risk RS+ MDS, an area in need of new treatments,” said Alise Reicin, MD, President, Global Clinical Development for Celgene. “Based on these results, we are encouraged that this first-in-class erythroid maturation agent may help these patients address the underlying cause of their disease-related chronic anemia.”
“It’s truly an honor to showcase the results from the MEDALIST trial as the first presentation of the ASH Plenary Session,” said Habib Dable, President and Chief Executive Officer of Acceleron. “The results from the MEDALIST trial increase our confidence in the potential of luspatercept to provide a meaningful treatment option for patients suffering from lower-risk RS+ MDS worldwide. We’re excited to continue our clinical development program in MDS, beta-thalassemia, and myelofibrosis, while also exploring additional applications for luspatercept in a range of diseases associated with anemia.”
Luspatercept is not approved in any region for any indication. The companies are planning regulatory application submissions of luspatercept in the United States and Europe in the first half of 2019.