Phase 2 Trial Updates on Sotatercept in Treating PAH Set for ATS 2021

Margarida Maia PhD avatar

by Margarida Maia PhD |

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Treatment with Acceleron Pharma’s sotatercept appears to be effective and generally well tolerated in people with pulmonary arterial hypertension (PAH), according to new data from the ongoing PULSAR and SPECTRA Phase 2 clinical trials.

These data will be presented at the American Thoracic Society (ATS) 2021 International Conference to be held virtually on May 14–19.

“It’s quite gratifying to return to the ATS International Conference with new sotatercept data, having first presented topline results from the PULSAR trial during a special breaking news session at ATS 2020 Virtual,” Habib Dable, president and CEO of Acceleron, said in a press release.

“The results to be shared this year strengthen our confidence in sotatercept’s potential to become a backbone therapy for patients with PAH,” Dable added.

The PULSAR and SPECTRA presentations are scheduled for Wednesday, May 19.

Sotatercept is a lab-made protein designed to rebalance signaling between pro- and anti-proliferative pathways, namely the bone morphogenic protein (BMP) signaling pathway that is known to play a key role in the maintenance of healthy lung blood vessels. Disturbances in the BMP pathway have been associated with the development of PAH.

In keeping with the top-line, 24-week findings announced in 2020, 48-week interim data from the open-label extension of the PULSAR Phase 2 trial (NCT03496207) shows consistent or improved responses in safety and efficacy measures with sotatercept’s use. These findings are detailed in the ATS 2021 abstract, “PULSAR study open-label extension: interim results from a Phase 2 study of the efficacy and safety of sotatercept when added to standard of care for the treatment of pulmonary arterial hypertension (PAH).”

The ongoing open-label extension is uncontrolled, meaning that patients previously on placebo are now being treated with sotatercept. Researchers found that the placebo did not affect the ability of patients to respond to sotatercept.

Specifically, sotatercept given every 21 days under the skin (subcutaneous injection) at a dose of 0.3 mg/kg or 0.7 mg/kg, in addition to standard-of-care therapy, increased the distance walked in the six-minute walk test (a test to measure exercise capacity), lowered levels of the N‐terminal pro‐brain natriuretic peptide (NT-proBNP, a marker of PAH severity), and reduced the World Health Organization (WHO) functional class (another measure of PAH severity) at 48 weeks compared with measures taken at 24 weeks, and at the beginning of the study.

PULSAR is due to conclude in May 2022.

The safety profile of sotatercept was consistent with that reported previously. Over these 48 trial weeks, 30 (28.3%) of the 106 patients enrolled experienced serious treatment-related adverse events; these events led to treatment discontinuation in nine (8.5%) patients and to death in two (1.9%) patients. The abstract does not give further details.

“In this first report of the open-label extension period of PULSAR, continued sotatercept treatment in patients with PAH suggests that clinical efficacy is maintained across multiple study endpoints for up to 48 weeks. Safety was consistent with previous reports in PAH and other patient populations,” the researchers wrote in the abstract. “These longer-term results highlight the versatility of sotatercept as a new treatment for PAH.”

In another abstract, titled “The SPECTRA study: a Phase 2a single-arm, open-label, multicenter exploratory study to assess the effects of sotatercept for the treatment of pulmonary arterial hypertension (PAH),” researchers share interim results from the SPECTRA Phase 2 trial (NCT03738150), which is assessing the efficacy and safety of sotatercept in PAH patients by invasive cardiopulmonary exercise testing (iCPET).

The trial’s main measure is the change in VO2 max (a measure of the maximal oxygen consumption during exercise) from the study’s start until 24 weeks (about six months). Preliminary data (Oct. 7 cutoff date) on 10 patients showed that sotatercept — given every 21 days under the skin at a starting dose of 0.3 mg/kg and escalating to 0.7 mg/kg, in addition to standard-of-care therapy — improved VO2 max at 24 weeks.

Other exercise hemodynamic (blood flow) parameters measured by iCPET were also improved.

Nine of these 10 patients reported treatment-related adverse events, and one discontinued treatment.

“In this preliminary analysis of patients in the ongoing SPECTRA study, encouraging results in hemodynamics and exercise tolerance and capacity were seen. Safety was consistent with previous reports in PAH and other patient populations,” the researchers wrote in the abstract.

These data also highlight “the clinical efficacy of sotatercept and its potential as a new treatment option for PAH patients,” the team added.

SPECTRA is due to finish collecting patient data in December 2021, and to conclude in December 2022.

These two ATS 2021 presentations will offer additional findings not in their abstracts.

At ATS 2021, Acceleron will also present preclinical data on the effects of sotatercept in animal models of PAH and pulmonary hypertension. The company is also planning to test sotatercept’s potential as a PAH therapy in multiple Phase 3 trials.