Acceleron’s post-Reblozyl plan comes together

Sotatercept’s win in pulmonary arterial hypertension positions Acceleron for a battle against the leaders in this crowded space.

So much for analyst fears that Acceleron’s valuation was running away from reality. With the group’s first drug, Reblozyl, off to a decent launch in beta-thalassaemia investor focus had switched to sotatercept, which promptly delivered a win in pulmonary arterial hypertension and sent the stock up 50% this morning.

The apparent mid-stage study success means that Acceleron’s second strategic pillar is in place. Pulmonary arterial hypertension (PAH) features entrenched players like Johnson & Johnson and United Therapeutics, but Acceleron claims that these groups’ drugs, unlike sotatercept, treat only the symptoms of the disorder.

Just two weeks ago Leerink analysts had expressed concern that Acceleron’s share price run-up suggested that the markets were ignoring the risks of the binary PAH data readout. Today they acknowledged that the latest data made for a “whole new story”, and more than doubled their price target for the company.


Though Leerink did not spell this out, a takeout thesis could underlie the Acceleron bull case. J&J became a big PAH player through its $30bn takeover of Actelion, while United might need to do deals as its efforts to remain a force in PAH are firing blanks (United Therapeutics fails to expand its Beat, April 8, 2019).

These companies’ products – J&J’s endothelin receptor antagonists Tracleer and Opsumit and prostacyclin agonist Uptravi, and United’s numerous incarnations of the prostacyclin analogue treprostinil – hold the lion’s share of the PAH market. This also includes repurposed erectile dysfunction drugs like Pfizer’s Revatio and Lilly/United’s Adcirca.

Crucially, these all basically act as vasodilators to relieve high blood pressure, and do nothing about the underlying reason why in PAH blood vessel walls thicken and cause hypertension to begin with.

Acceleron argues that sotatercept, which blocks the TGF-beta superfamily pathway, is different, acting to rebalance the BMPR2 signalling whose disruption it claims promotes cell proliferation and vascular remodelling in PAH.

Yesterday’s results, from sotatercept’s Pulsar trial, back up such a claim, though for now the company is not revealing any numerical data.

But the signs are good. Even though the 106 Pulsar subjects were on existing PAH therapies sotatercept yielded a statistically significant reduction in week-24 pulmonary vascular resistance versus placebo, the primary endpoint. Several secondary efficacy measures were also hit, and importantly the study did not show significant toxicity issues.

Sotatercept is also in a separate small phase II PAH study, Spectra, though this is described as an exploratory trial. The bottom line is that approval will depend on a pivotal programme encompassing between 700 and 1,200 subjects; not only will this be costly, it will take several years to complete.

This is where business development could come into play, though Acceleron might also want to stay independent to retain more of sotatercept’s value. The asset had been licensed to Celgene, now owned by Bristol-Myers Squibb, but that company had stepped back from development to focus on Reblozyl and retain a royalty interest.

There are other considerations, of course, such as the competitive nature of selling PAH drugs, and other industry projects in the pipeline. Still, pending the full Pulsar data readout, there should now be increased interest in sotatercept.

Selected PAH projects in the pipeline
Project Company Mechanism 2024e sales ($m)
Phase III
INOpulse Bellerophon Therapeutics Wearable system to inhale nitric oxide while on the go 122
Ralinepag United Therapeutics/Arena Prostacyclin agonist 107
Aurora-GT United Therapeutics/Northern Endothelial nitric oxide synthase gene therapy
Phase II
Sotatercept Acceleron/BMS ACT2RB fusion protein 46
JTT-251 Japan Tobacco Pyruvate dehydrogenase kinase inhibitor
Tacrolimus Vivus Calcineurin inhibitor
QCC374* Novartis Prostacyclin agonist
Source: EvaluatePharma; *study terminated for "strategic reasons" in 2019.

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