Acceleron to Launch Phase 3 Trial Testing Sotatercept by Year’s End

Acceleron Pharma announced plans to launch the first Phase 3 clinical trial, called STELLAR, evaluating the safety and effectiveness of its investigational therapy sotatercept (ACE-011) in people with pulmonary arterial hypertension (PAH), before the end of the year.

Two other Phase 3 trials testing sotatercept as an early intervention (the HYPERION study) or a later-stage treatment (the ZENITH study) in expanded PAH patient populations are expected to start in mid-2021.

Meant to support future submissions to regulatory authorities seeking the therapy’s approval for PAH at all stages, these studies are the result of the “finalization of the global regulatory path for sotatercept in PAH,” Habib Dable, Acceleron’s president and CEO, said in a press release.

Acceleron also plans to present latest data from its ongoing Phase 2 trials — PULSAR (NCT03496207) and SPECTRA (NCT03738150), evaluating sotatercept in PAH patients with moderate physical limitations — at the American Heart Association (AHA) 2020 Scientific Sessions virtual meeting, which begins today and runs through Tuesday.

“Encouraged by the impressive topline results from our PULSAR Phase 2 trial, we look forward to multiple presentations on sotatercept at the upcoming virtual meeting of the AHA 2020 Scientific Sessions … as our team is preparing to initiate our registrational Phase 3 trial …” Dable said.

Sotatercept, given through under-the-skin injections, is a lab-made protein designed to bind and trap members of the TGF-beta superfamily, including those involved in bone morphogenic protein (BMP) signaling — known to play a key role in the maintenance of healthy lung blood vessels.

Since disturbances in BMP signaling in the lungs are thought to drive PAH development and progression, sotatercept is expected to help restore BMP balance and prevent further damage.

Preclinical studies in animal models of PAH showed that sotatercept reduced pulmonary arterial pressure and eased pulmonary vascular remodeling and indicators of heart’s right ventricle failure — all hallmarks of PAH.

Top-line results from the international PULSAR study, testing two doses of sotatercept against a placebo in 106 adults with PAH, showed that about six months of sotatercept treatment safely and effectively eased patients’ heart strain and disease severity, and improved their functional capacity.

Most participants — who had moderate physical limitations (World Health Organization functional class II–III) — chose to enter the trial’s open-label extension phase, in which all will receive sotatercept for an additional 18 months.

SPECTRA is evaluating the effects of nearly six months of treatment with sotatercept, in addition to standard therapy, in up to 25 adults with PAH and functional class III. According to its page, the trial is currently recruiting participants at several locations in the U.S.

According to the release, results from PULSAR’s open-label extension period and additional SPECTRA data are expected in the first half of 2021.

The upcoming pivotal Phase 3 trial STELLAR (NCT04576988) is designed to investigate the safety and effectiveness of sotatercept, in addition to stable doses of background standard care, in up to 284 adults with PAH and functional class II–III.

Participants will be assigned randomly to receive an under-the-skin injection of either sotatercept or a placebo, once every three weeks for 24 weeks (nearly six months).

STELLAR’s main goal is to assess whether sotatercept is superior to placebo at improving patients’ exercise/functional capacity — as assessed with the six-minute walk test (6MWT).

Its key secondary goal is determining the proportion of patients achieving specific improvements in three distinct measures — 6MWT, NT-proBNP levels, and functional class — included in a new, multicomponent assessment. Of note, NT-proBNP is a standard marker of cardiac stress and a prognostic biomarker of PAH.

Other secondary goals include changes in pulmonary vascular resistance (a measure of heart strain), health-related quality of life, and time to disease worsening or death.

Participants completing the trial will be eligible to continue or initiate sotatercept treatment in a separate, open-label extension study.

To date, no further details have been provided regarding the HYPERION and ZENITH Phase 3 trials.

Sotatercept received orphan drug and breakthrough therapy designations in the U.S. and priority medicines designation in the European Union for the treatment of PAH. These designations are intended to accelerate the therapy’s development and regulatory review.