A phase 3 trial of Celgene’s luspatercept in adults with beta thalassemia has hit its primary goal. The late-phase success tees Celgene to file for approval of its Acceleron-partnered blockbuster prospect in the first half of next year.

Celgene’s trial assessed the ability of erythroid maturation agent luspatercept to reduce the need for adults with anemia related to beta thalassemia to undergo red blood cell transfusions. Luspatercept was tipped to drive improved outcomes by targeting TGF-beta proteins involved in the maturation of red blood cells.

The 336-subject phase 3 trial provided further evidence to support the use of luspatercept. About one-fifth of participants who received luspatercept every three weeks experienced a 33% reduction in transfusion burden during weeks 13 to 24 of the trial, compared to 5% of people on placebo. That resulted in the trial hitting its primary endpoint.

Celgene reported successes against secondary objectives, too. The difference between the performance of luspatercept and placebo continued into weeks 37 to 48 of the study. Significantly more people who took luspatercept experienced reduced transfusion burden across any 24 weeks of the 48-week trial.

With the safety profile coming in relatively clear, the results add to the impression that Celgene has a data set capable of supporting the approval of luspatercept. The other piece of the data set comes from a phase 3 trial in myelodysplastic syndromes (MDS) that reported results in June.

Celgene and the analysts that cover it think the data suggest luspatercept could rack up peak sales of about $2 billion, with MDS accounting for upward of two-thirds of those revenues. If that happens, the deal for luspatercept will mark a high point for Celgene’s business development team. Celgene picked up the rights for luspatercept, then known as ACE-536, for $25 million upfront and up to $217 million in regulatory and commercial milestones in 2011.

The business development team, which has overseen its fair share of dud deals, will be hoping its big bet on Juno Therapeutics will also deliver a return. Juno, once a CAR-T forerunner, fell well behind Novartis and Gilead’s Kite Pharma after running into safety problems.

JCAR017, which replaced JCAR015 as Juno’s lead candidate following patient deaths, is making its way through a pivotal trial in lymphoma. But with Kymriah and Yescarta already on the market in lymphoma, the CAR-T therapy may have a better chance of making an impact in indications not yet addressed by the market leaders.

New data suggest chronic lymphoblastic leukaemia (CLL) could provide Celgene with such an opportunity. In a 16-patient trial, 13 subjects with CLL responded to JCAR017. Seven of the patients experienced complete responses. A separate CLL study linked concurrent use of JCAR014, a sibling of JCAR017, and Imbruvica to an overall remission rate of 83% and no cases of cytokine storm.

After attending a presentation of the CLL data, Jefferies analysts wrote that "there was overwhelming surprise positive commentary from the panel and audience" and talked up the potential for Celgene to target a blockbuster CAR-T opportunity.

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