If there was whooping and high-fiving in Celgene’s boardroom yesterday you can hardly blame the C-suite for their exuberance. The company was desperate for its Acceleron-partnered project luspatercept to come through, and yesterday’s positive readout of its most important study to date ended a disastrous run of missteps.
While no numbers have been released from the trial the signs are that the data are strong, But it is a separate study, yet to begin, that will make the difference between luspatercept being a good seller and a great one.
That new study, Commands, will test luspatercept in the broad first-line population of patients with myelodysplastic syndromes (MDS) who have not received erythropoietin-stimulating agents. Yesterday’s success, in the Medalist trial, concerned MDS patients with ringed sideroblasts – a high-responder group – who had failed on or were ineligible to receive erythropoietin-stimulating agents.
Acceleron’s stock was up 40% this morning on the topline news: Medalist had met its primary endpoint of red blood cell transfusion independence of at least eight consecutive weeks during the first 24 weeks versus placebo, as well as hitting two important secondary measures. Full data will be presented at December’s Ash meeting, Leerink analysts reckon.
Expectations had already been high (Event – Can Acceleron stem Celgene’s bleeding?, June 11, 2018). The magic number for eight-week transfusion independence appears to have been 30%, according to Evercore ISI; Acceleron previously said a 27-39% response rate would constitute a win.
Indeed, Medalist was powered to detect a 30% response versus 10% for control. Celgene and Acceleron’s description of primary efficacy analysis as yielding “highly statistically significant improvement” suggests that the magic 30% has been hit. A separate trial, Believe, testing luspatercept in beta-thalassaemia, is due to read out imminently.
However, neither Medalist nor Believe will enable the asset to sell $2bn, Evercore ISI’s peak revenue forecast. This number will depend on success in Commands. EvaluatePharma’s consensus of sellside forecasts sees MDS broadly yielding $499m of 2024 sales, versus $395m for beta-thalassaemia.
In the meantime luspatercept is to be filed for MDS in the US and Europe in the first half of next year – an unusually long wait given that the companies are suggesting that in Medalist they already have the necessary data for regulators.
Perhaps Celgene, which recently suffered the embarrassment of a refusal-to-file letter from the FDA over ozanimod, wants to make absolutely certain that in this case the regulatory package is watertight. That snafu had come after the failure of mongersen and the scrapping of Celgene’s long-term forecasts, all at a time when its cash cow, Revlimid, is looking increasingly vulnerable.
No matter how much still needs to be proved with luspatercept, after this run of disasters Celgene is today breathing a sigh of relief.
|Selected luspatercept trials|
|Medalist||2nd-line MDS||"Highly statistically significant" improvement||NCT02631070|
|Believe||Transfusion-dependent beta-thalassaemia||Due H1 2018||NCT02604433|
|Commands||1st-line MDS||Starting imminently||None yet|