On June 28, Celgene and Acceleron announced that their lead product candidate luspatercept (ACE-536) met its primary and secondary endpoints in two key Phase III trials, Medalist and BELIEVE, evaluating the agent in myelodysplastic syndromes (MDS) and β-thalassemia, respectively.

These indications are characterised by defects in red blood cell (RBC) maturation. Discovered by scientists at Acceleron, luspatercept is a first-in-class erythroid maturation agent (EMA) that targets specific TGF-beta proteins that play roles in late-stage RBC maturation. Acceleron and Celgene’s collaboration on luspatercept started in 2011 when the companies announced a joint agreement to develop, manufacture, and commercialise this novel drug for the treatment of anemia across a wide range of indications. For this alliance, Celgene made an upfront payment of $25M to Acceleron and signed on an additional agreement permitting Acceleron to receive milestone payments of up to $217M.

The MEDALIST trial was a randomised, double-blind, placebo-controlled study that assessed the safety and efficacy of luspatercept in patients who are categorised as having very low, low, or intermediate risk  MDS with ring sideroblasts requiring constant RBC transfusion according to the revised International Prognostic Scoring System (IPSS-R). Enrolled patients were either refractory, intolerant, or had a low chance of response to the current treatments with erythropoiesis-stimulating agents, Janssen ’s Eprex (epoetin alfa) or Amgen ’s Aranesp (darbepoetin alfa).

Positive trial results and clinical studies

Luspatercept achieved a highly statistically significant improvement in the primary endpoint of RBC transfusion independence compared to placebo for eight consecutive weeks during the first 24 weeks of the study. As there are limited options to treat anemia in patients with MDS, a hematologic disorder characterised by the ineffective differentiation and maturation of blood cells, luspatercept represents a big step forward in managing disease progression and improving quality of life.

Within two weeks of the news from the MEDALIST trial, Celgene and Acceleron announced positive results from their second Phase III study, BELIEVE, which evaluated the efficacy and safety of luspatercept + best supportive care versus placebo + best supportive care in adults with beta-thalassemia. This randomised, double-blind, multi-centre clinical study met a pivotal primary endpoint by successfully alleviating RBC transfusion burden by 33% in the patient cohort that received luspatercept.

Encouraged by the strong efficacy readouts in the MEDALIST and BELIEVE studies, the companies are pursuing an aggressive clinical development programme that will evaluate the candidate in treatment-naive MDS patients (COMMANDS), non-transfusion-dependent beta-thalassemia (BEYOND), and myelofibrosis, a rare bone marrow disorder.

The top-line results from MEDALIST and BELIEVE came at a time when Celgene faced disappointment in results from its clinical candidates in the past years. With the patent for Celgene’s blockbuster drug Revlimid (lenalidomide)‎ expiring soon, luspatercept’s estimated annual sales of more than $2B are expected to boost both its revenue and investor’s confidence in the company’s pipeline.

Acceleron and Celgene plan to present data from the clinical studies in medical meetings, and submit applications for the approval of luspatercept in the US and Europe in Q1 2019 for the studied indications. Due to its strong clinical efficacy in the MEDALIST study and the lack of competition from currently available drugs to treat anemia, luspatercept has high potential to quickly dominate the market following its launch in MDS.