The U.S. Food and Drug Administration (FDA) has granted the designation of breakthrough therapy to Acceleron Pharma‘s investigational molecule sotatercept for the treatment of pulmonary arterial hypertension (PAH).

Breakthrough designation is given to medications that have the potential to provide significant advantages over currently available options. It is intended to accelerate the development, review, and approval of treatments for serious or life-threatening conditions.

This designation follows sotatercept’s inclusion in the FDA’s orphan drug program in 2019 which, among other incentives, provides a seven-year period of marketing exclusivity if the treatment receives regulatory approval.

“[W]e’re thrilled that the FDA has granted this Breakthrough Therapy designation — a first for an Acceleron-discovered medicine and for a therapeutic candidate in PAH — as it supports and aligns with our mission to deliver novel therapeutic options to patients in need as quickly as possible,” Habib Dable, president and CEO of Acceleron, said in a press release.

Sotatercept is an investigational compound that works to counteract the abnormal bone morphogenic protein (BMP) signaling in the lungs, believed to be a critical driver of the vascular remodeling processes that contribute to PAH development and progression.

It does so by binding and trapping proteins of the transforming growth factor-beta (TGF-beta) family — which control numerous aspects and effects of cell functions — especially those directly involved in the BMP pathway.

By restoring the balance of BMP signaling, sotatercept is believed to improve the health of pulmonary arteries and reduce pulmonary arterial pressure, ultimately lowering the risk of heart failure.

An ongoing Phase 2 trial, named PULSAR (NCT03496207), is assessing the safety and efficacy of sotatercept as an add-on treatment for people with PAH.

The double-blind trial enrolled 106 participants, who were randomly assigned to receive one of two doses of sotatercept — 0.3 or 0.7 mg/kg — or a placebo, while continuing their standard of care therapies. Treatment was given once every three weeks via a subcutaneous (under-the-skin) infusion, for a total of 24 weeks (about six months).

The trial’s main goal was to demonstrate whether sotatercept is better than placebo at reducing pulmonary vascular resistance — a measure of heart strain assessed through right heart catheterization — after six months.

That goal was met, according to topline data announced earlier this year, along with several other secondary endpoints of PULSAR. In addition to inducing a significant drop in patients’ heart strain compared to placebo, sotatercept also significantly improved the patients’ exercise tolerance (a key secondary measure), reduced disease severity, and lowered markers of heart failure.

Sotatercept was generally well-tolerated, and had a safety profile consistent with previous reports. Detailed results from the study will be presented at a medical meeting later this year.

“In January of this year, we reported positive topline results from our PULSAR Phase 2 placebo-controlled trial of sotatercept in patients with PAH,” said Dable. “Based on the results, we believe that sotatercept has the potential to shift the current treatment paradigm, and provide significant benefit to patients with PAH on top of currently available therapies.”

Apart from PULSAR, Acceleron is also conducting another Phase 2 study, called SPECTRA (NCT03738150), assessing sotatercept in PAH patients.