Celgene has filed luspatercept with the FDA, a novel treatment for patients with two blood disorders who depend on red blood cell (RBC) transfusions, myelodysplastic syndromes (MDS)-associated anaemia and beta-thalassemia-associated anaemia.
The drug is one of five late-stage pipeline drugs from Celgene tipped for blockbuster status (the first being the just-re-filed ozanimod) and the filing comes just days ahead of a key vote on the company’s $74bn buyout by BMS on Friday.
The filing will further boost momentum behind the merger, which had been in doubt when some investors challenged the wisdom of the deal. Shareholders now look odds-on to approve the merger, however, and the newly enlarged BMS will look to luspatercept to be among its new growth drivers.
Analysts believe the subcutaneous injectable drug could hit peak sales of about $2bn, with MDS accounting for two-thirds or more of these revenues.
Filing for MDS is based on the phase 3 MEDALIST trial in adults with ring sideroblast (RS+) myelodysplastic syndromes (MDS)-associated anaemia with very low, low, or intermediate-risk of the condition developing into acute myeloid leukaemia (AML).
The trial showed significant results in its primary endpoint of at least eight weeks without the need for a transfusion: around a third of previously transfusion dependent patients were transfusion independent (TI) over weeks 1-48 of the trial, as opposed to just 11% in the placebo arm.
The drug also showed some significant results in Celgene’s BELIEVE trial in beta-thalassemia, but could only reduce their need for transfusions in these patients (by around a third) rather than free them from the procedure entirely.
The beta thalassemia market will prove tougher to crack for this reason, and also because Bluebird’s newly CHMP-recommended gene therapy Zynteglo offers patients a cure in a single treatment.
Luspatercept’s eventual approval will be a rare case of highly value-creating in-licensing from Celgene: the firm signed the deal with Acceleron in 2011 for $25m upfront and up to $217m in regulatory and commercial milestones. This is in contrast to several other in-licensed molecules which have failed to recoup their high acquisition costs.
The drug will be a new option for patients in both categories, for whom the primary treatment is currently chronic transfusion of red blood cells, which can result in complications such as iron overload.
Celgene’s Jay Backstrom
Jay Backstrom, chief medical officer for Celgene commented: “New treatment options are urgently needed for these patients. With this submission, we look forward to working with the Agency to deliver luspatercept to patients with these serious blood diseases.”
The companies also plan to submit a marketing application to the European Medicines Agency in Q2 of 2019.
Luspatercept is a first-in-class erythroid maturation agent (EMA) that regulates late-stage red blood cell maturation.
Celgene and Acceleron have further plans for its development: it is currently in a phase 3 trial (COMMANDS) in erythropoiesis stimulating agent (ESA) naïve, lower-risk MDS patients. It is also being studied in the BEYOND phase 2 trial in non-transfusion-dependent beta-thalassemia, and a phase 2 trial in myelofibrosis.