On December 19, 2018 Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ: XLRN) reported its results from the pivotal Phase III trial MEDALIST in early December 2018 (Press release, Celgene, DEC 19, 2018, View Source [SID1234532160]). The study evaluated the efficacy and safety of the investigational product luspatercept for the treatment of patients suffering from anemia due to ring dermoblast-positive (RS +) myelodysplastic syndrome (MDS), transfusions with packed red blood cells (EC), and where erythropoietin therapy was unsuccessful , there was an intolerance to it or such therapy was out of the question. The results were Alan F. List during the scientific plenary session on the 60th

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"Severe anemia leading to red blood cell transfusion dependence is a significant burden for patients at low risk MDS. For patients who become resistant or refractory to currently available therapies, there are only limited alternatives, "said Drs. List, President and CEO of the Moffitt Cancer Center. "The results from the MEDALIST study are very promising. They support the hypothesis that luspatercept promotes the maturation of erythroid progenitor cells, allowing patients to become transfusion-independent. Luspatercept could thus improve the treatment of anemia in RS + MDS patients. "

The MEDALIST trial reached its primary endpoint: A statistically significantly greater proportion of patients achieved RBC-TI independence of ≥ 8 weeks in the first 24 weeks of treatment with luspatercept compared to placebo. In addition, all important secondary endpoints of the study were achieved. Compared to placebo, a significantly greater proportion of patients in the luspatercept arm achieved RBC-TI ≥ 12 weeks in the first 24 and 48 weeks of study, respectively, and hematologic erythropoiesis (HI-E after IWG 2006) of 8 weeks or more.

endpoints Luspatercept placebo p-value
RBC-TI ≥ 8 weeks (Week 1-24) 37.9 % (58/153) 13.2 % (10/76) <0.0001
RBC-TI ≥ 12 weeks (Week 1-24) 28.1 % (43/153) 7.9 % (6/76) 0.0002
RBC-TI ≥ 12 weeks (Week 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

Summary of safety data from the MEDALIST study

Third or fourth degree treatment-associated adverse events (TEAEs) were observed in 42.5% (65/153) of patients receiving luspatercept and 44.7% (34/76) of patients receiving placebo. Disease progression to acute myelogenous leukemia (AML) occurred in a total of four patients: three patients (2.0%) treated with luspatercept and one patient (1.3%) receiving placebo. Five patients receiving luspatercept (3.3%) and four patients receiving a placebo (5.3%) experienced one or more TEAEs that were fatal.

The most common TEAEs of any grade in more than 10% of patients in either study arm

Luspatercept
n = 153

placebo
n = 76

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 results of the MEDALIST study illustrate the potential clinical benefits of Luspatercept to make patients with RS + low-risk MDS less dependent on red blood cell transfusion. This is an area where new therapies are needed. " med. Alise Reicin, President of Global Clinical Development at Celgene. "These findings reinforce our belief that this first-in-class erythropoietic-based drug can help these patients address the underlying cause of their disease-related chronic anemia."

"It is a great honor to present the results of the MEDALIST study as the first presentation at the ASH (Free ASH Whitepaper) plenary session," said Habib Dable, President and Chief Executive Officer of Acceleron. "The results of the MEDALIST study give us confidence that luspatercept can provide a relevant treatment option for patients with low-risk RS + MDS anywhere in the world. We look forward to continuing our clinical development program for MDS, beta-thalassemia and myelofibrosis, while investigating other applications of luspatercept in a variety of anemia-related diseases. "

Luspatercept is not approved in any region and for no indication. Acceleron and Celgene are planning to submit regulatory filings for Luspatercept in the US and Europe in the first half of 2019.

About MEDALIST

MEDALIST is a randomized, double-blind, placebo-controlled, multicentre phase III trial to evaluate the safety and efficacy of luspatercept in patients with very low, low or medium risk RS + myelodysplastic syndromes (MDS). All patients were RBC transfusion-dependent and either refractory to previous therapy with erythropoiesis-stimulating agents (ESA), did not tolerate them or were ESA naive with endogenous serum erythropoietin ≥200 U / L and had no previous treatment with disease modifying agents receive. The median age of the study participants was 71 years in the luspatercept treatment group and 72 years in the placebo group. The mean transfusion load in both study arms was 5 RBC units / 8 weeks. A total of 229 patients were randomized to receive either luspatercept 1.0 mg / kg (153 patients) or placebo (76 patients) every 21 days as a subcutaneous injection. The study was conducted at 65 sites in 11 countries.

About Luspatercept

Luspatercept, the erythrocyte-ripening substance, is the first active ingredient in a new erythroid maturation agent (EMA). It promotes erythrocyte maturation in the late stages of erythropoiesis. Acceleron and Celgene are developing Luspatercept as part of a global collaboration. Phase III clinical trials are evaluating the safety and efficacy of luspatercept in patients with MDS (MEDALIST trial) and patients with beta thalassemia (BELIEVE trial). The COMMANDS phase III study in low-risk first-line MDS patients, the BEYOND non-transfusion-dependent beta-thalassemia phase II study and a phase II study in myelofibrosis are ongoing. For more information, seewww.clinicaltrials.gov .