In recent times Celgene’s name has hardly been synonymous with canny deal making. But the beleaguered biotech finally seems to have made a smart bet with luspatercept, licensed from Acceleron for just $25m seven years ago.
Celgene believes that the project could become a $2bn drug, and positive data presented at the Ash meeting today go some way to justifying its optimism. But any Acceleron investors also hoping for a big pay day might end up disappointed: the smaller company is due to receive future milestones of just $185m, though royalties will of course also be due. With Celgene firmly in the driving seat the prospects of a full buyout appear unlikely.
Small change for Celgene
The next milestone, of $25m, will come upon luspatercept’s first filing with either the US FDA or European Medicines Agency, Acceleron’s chief executive, Habib Dable, told Vantage on the sidelines of the Ash conference.
The companies plan to submit luspatercept for approval in the first half of 2019 in beta-thalassaemia and a subtype of patients with myelodysplastic syndromes: those with ringed sideroblasts who have failed on or are ineligible to receive erythropoietin-stimulating agents.
Mr Dable insisted that Acceleron was “very pleased” with the terms of the deal – but pointed out that he had not been at the company when the agreement was struck. He added that Acceleron would also receive royalties in the low 20% range initially, rising to the “mid-20s”, and that Celgene would cover “all the costs”, including those for Acceleron’s sales force; the companies have agreed to co-promote the asset in North America.
Might Celgene also be interested in Acceleron’s other assets? It seems unlikely: Celgene had previously partnered with the smaller group on another TGF-beta-targeting project, sotatercept, but handed back rights two years ago. Acceleron is now developing the project alone for pulmonary arterial hypertension.
The company also has ACE-083, in phase II for Charcot-Marie-Tooth disease and facioscapulohumeral muscular dystrophy, and the phase I neuromuscular project ACE-2494.
Mr Dable refused to be drawn on any speculation that Celgene might be interested in buying Acceleron, saying he was focused on building the company and its pipeline.
For now, the success of that company hinges on luspatercept.
Data presented at Ash today, from the Medalist trial in MDS, and the Believe trial in transfusion-dependent beta-thalassaemia, were broadly in line with those previously detailed in November’s abstract drop (Ash 2018 preview – smaller groups get their turn in the spotlight, November 21, 2018).
There were some new nuggets of information from Medalist: the median duration of response was 31 weeks in luspatercept-treated patients, compared with around 10 weeks in the control arm. And transfusion independence was maintained in 40% of luspatercept patients for a year or longer.
Beta-thalassaemia and the Medalist MDS population respectively account for 20,000 and 40,000 patients across the US and Europe, Mr Dable estimated.
Luspatercept will be able to address another 25,000 patients in these territories if it prevails in another ongoing trial, Commands, which is testing the drug head to head against epoietin alfa in first-line MDS patients who have not previously received erythropoietin-stimulating agents. Mr Dable would not give more details about when that is due to report.
Dr Alan List, of the Moffitt Cancer Center in Florida, predicted success for Commands, saying he expects luspatercept to be more effective than ESAs.
Celgene and Acceleron are also testing luspatercept in myelofibrosis and non-transfusion-dependent beta-thalassaemia.
Gene therapy threat?
When asked how luspatercept might fit in with incoming gene therapies for beta-thalassaemia, Dr Maria Domenica Cappellini of the Fondazione IRCCS Ca’ Granda Policlinico Hospital in Milan, replied: “Gene therapy must be a cure. You’re not going to perform gene therapy for reducing transfusion burden.” She added that there was “still a way to go to achieve this”.
One potential advantage of luspatercept over gene therapies is the avoidance of busulfan preconditioning regimens. This chemotherapy is used to damp down patients’ immune systems before therapy but is linked with serious side effects.
Busulfan was blamed today for a case of myelodysplasia in an ongoing study of Bluebird’s Lentiglobin in sickle cell disease – specifically, group A of the phase I/II HGB-206 study, using the original manufacturing method that produced disappointing results at Ash three years ago.
More important data from group C of the trial, using a new manufacturing process, are due on Monday, but investors will now be watching out for any more adverse events.
Bluebird is also developing Lentiglobin in beta-thalassaemia, where it one day might go up against luspatercept.
Today the company presented data from the completed phase I/II Northstar trial. Again this used the original manufacturing process for Lentiglobin, which Bluebird has since refined – but it did show impressive durability, at least in patients who responded.
Again, investors will have to wait a bit longer for the main event. Another Lentiglobin update on Monday will come from two trials using the new manufacturing process: Northstar-2, in patients with the non-β0/β0 genotype, who produce some haemoglobin; and Northstar-3, in more severely affected patients with the β0/β0 genotype, who do not produce any haemoglobin.
Bluebird has filed Lentiglobin in Europe in non-β0/β0 patients. Nick Leschly, the group’s chief executive, would not say when the company would file for US approval, but told Vantage: “It’s not in the too distant future.”