Second positive trial sets up filings for Acceleron’s blood disorder drug luspatercept

Acceleron and Celgene have the second phase 3 trial they wanted for beta thalassemia drug luspatercept, setting up filings in the U.S. and Europe for the first half of 2019.

The new data from the BELIEVE study suggests that luspatercept could provide a new treatment option for patients with the rare inherited blood disorder, which causes severe anemia. Beta thalassemia is currently treated with regular blood transfusions, which can cause iron overload, requiring drug treatment to strip excess iron out of the blood.

Compared to placebo, luspatercept was able to reduce the number of red blood cell transfusions needed in transfusion-dependent patients, say Acceleron and Celgene. Their drug hit the primary objective of achieving an erythroid response—a 33% reduction in transfusion burden with a reduction of at least two units—over a 12-week assessment period from weeks 13 to 24 of the study.

Luspatercept, which boosts the production of red blood cells by targeting TGF-beta proteins involved in red cell differentiation and maturation, also met secondary objectives in the trial including achieving a 50% reduction in transfusion in the main assessment period as well as between weeks 37 and 48.

BELIEVE follows positive results in the MEDALIST study in patients with myelodysplastic syndromes (MDS) and chronic anemia, which were reported late last month. There are no approved drugs for anemia in these patients, and analysts at Evercore have suggested that luspatercept could become a $2 billion product if approved across the phase 3 indications.

The two partners are currently preparing a phase 3 trial, called COMMANDS, to compare luspatercept head-to-head with red blood cell stimulator epoetin alfa in treatment-naïve MDS patients. They also have phase 2 trials on the go in non-transfusion-dependent beta-thalassemia (BEYOND) and myelofibrosis, a rare bone marrow disorder. 

“The BELIEVE study marks the second positive phase 3 study for luspatercept and underscores the potential of this erythroid maturation agent to impact a range of diseases associated with chronic anemia,” said Habib Dable, Acceleron’s CEO, in a release.

Acceleron and Celgene have been working on the TGF-beta program for a decade, initially focusing on a drug called sotatercept that was replaced by luspatercept as the lead candidate in the blood disorders program. It’s an important drug for Celgene, which has suffered a string of pipeline setbacks over the last few months, including the failure of mongersen and the FDA refusal-to-file for ozanimod, and is still trying to prepare for the future patent expiry on cash cow Revlimid.

Meanwhile, Acceleron has had its own R&D stumbles of late. Last year, its advanced renal cell carcinoma candidate dalantercept was abandoned after a failed phase 2 trial.