Celgene puts the spotlight on Acceleron

Celgene’s prioritisation of the Acceleron-partnered luspatercept will put another promising candidate into the late-stage pipeline for myelodysplastic syndromes, and sees an interesting strategic separation between it and its sister project, sotatercept.

Both assets are partnered with Celgene, and the move confirms Acceleron as one of Celgene’s key mid-stage partners. But an observer would have a hard time working this out from the market reaction: Acceleron’s stock has fallen over 30% since stellar data with luspatercept and sotatercept were presented at ASH last December.

Those results related to luspatercept in beta-thalassaemia and sotatercept in myelodysplastic syndromes (MDS), but after Celgene’s decision last Thursday work on the latter will now focus on chronic kidney disease rather than MDS (ASH – Recent biotech floaters show their worth, December 08, 2014).

Not that this should surprise anyone; it was always the plan that Celgene would prioritise one asset. Sotatercept and luspatercept are both activin type II receptor fusion proteins that act on late-stage erythropoiesis to increase mature erythrocyte release, and thus have the potential to treat anaemia – a symptom of MDS.

Luspatercept’s ongoing open-label phase II trial, Pace-MDS, in low-risk patients, was highlighted at last week’s International Symposium on MDS.

The study has completed enrolment of 58 patients and is treating them with 0.125-1.75mg/kg doses, and preliminary results on 44 patients showed that 47% hit the primary outcome measure of modified erythroid response. At ASH sotatercept’s 53-patient phase II trial had shown an erythroid response in 45%, though this tested a lower dose range, 0.1-1.0mg/kg.

But researchers last week highlighted luspatercept’s result in high-dose patients and those with ring sideroblasts (RS) – abnormal red blood cell precursors. In the 0.75-1.75mg/kg high-dose group 54% of patients hit the primary outcome measure, while in the high-dose subgroup of those with RS the percentage was 63%.

Luspatercept should start phase III this year – an event that might trigger a Celgene milestone under the companies’ 2008 licensing deal. JMP analysts said the phase II data removed much of the risk of luspatercept, whose commercial potential in MDS and beta-thalassaemia remained underappreciated.

Nasdaq woes

This view is borne out by Acceleron’s underwhelming 39% rise since a September 2013 IPO, though this easily beats the 89% crash suffered by Onconova, another MDS-focused 2013 Nasdaq entrant.

Onconova also used the International Symposium on MDS to highlight its lead asset, rigosertib. These presentations included a post-mortem of rigosertib’s phase III trial, Onetime, whose failure to show a survival benefit in high-risk MDS patients led to its partner Baxter declining to “pursue additional trials”, though the collaboration has not formally been canned.

There was better news for another Baxter licensor, Merrimack, with the European filing of MM-398 for treating metastatic pancreatic adenocarcinoma after gemcitabine chemo. Although this project had shown a meagre 1.9 month’s additional survival in this setting, the lack of other options probably bodes well.

The Baxter setback has left Onconova to fund a new pivotal trial of rigosertib, in a more homogeneous high-risk patient population, on its own. The assumption that the group will need to raise more cash, cost-cutting notwithstanding, cannot be helping the stock; Onconova ended 2014 with $43.6m in the bank.

Acceleron, meanwhile, boasted $176.5m of year-end cash, and with Celgene funding its two lead assets it seems remarkably well placed. A third project, dalantercept, is in phase II trials in several tumour types, but is fully owned by Acceleron.

If nothing else, the lack of additional licensees makes Acceleron a clean asset should Celgene want to make its hold over luspatercept and sotatercept somewhat more permanent.

Project Study Trial ID
Luspatercept Pace-MDS NCT01749514
Sotatercept NCT01736683
Rigosertib Ontime NCT01241500

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter

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