FDA Grants Priority Review to Sotatercept for Pulmonary Arterial Hypertension

Granted a PDUFA date in March 2024, if approved, sotatercept would be a first-in-class medication to address the rare and progressive disease.

Credit: US Food and Drug Administration

Key Highlights

FDA has set a PDUFA date of March 26, 2024.
BLA is based on clinically meaningful results from the phase 3 STELLAR trial.
Pending approval, sotatercept would be a first-in-class, medication to treat PAH.

The US Food and Drug Administration (FDA) has accepted for priority review a new biologics license application (BLA) for sotatercept, a novel investigational activin signaling inhibitor, for the treatment of adults with pulmonary arterial hypertension (PAH).¹

Announced by Merck on September 28, the FDA has set a Prescription Drug User Fee Act (PDUFA) date of March 26, 2024.

“Despite advances in the treatment of PAH over the last 2 decades, there is still a significant need to improve outcomes for patients,” said Joerg Koglin, MD, PhD, senior vice president, global clinical development, Merck Research Laboratories.¹ “The FDA’s acceptance of this application is an exciting milestone in our journey to bring this novel activin signaling inhibitor to patients.”

A rare, severe disease, PAH is characterized by the narrowing of blood vessels in the lungs, leading to a significant strain on the heart. Approximately 40,000 people in the US live with the disease, the disease progresses rapidly for many patients. It has been linked to limited physical activity, heart failure, and reduced life expectancy, with a 5-year mortality rate of approximately 43%.

Sotatercept is a potential first-in-class activin signaling inhibitor biologic being studied for the treatment of PAH. The BLA for the treatment was based on data from the Phase 3 STELLAR trial. STELLAR was a pivotal phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study evaluating the safety and efficacy of sotatercept in adult patients with PAH being treated with background therapy with WHO Functional Class II or III.

Presented at the 2023 American College of Cardiology (ACC) Annual Scientific Sessions, the results showed sotatercept on top of background therapy led to a statistically significant and clinically meaningful improvement in 6-minute walk distance. In addition, sotatercept met 8 of 9 secondary endpoints, including the proportion of participants achieving multi-component improvement.²

Accompanying STELLAR, the sotatercept clinical development program includes multiple phase 2 and 3 trials across a wide range of patients. Trials are being performed in adult patients with PAH at intermediate or high risk of disease progression of mortality, as well as those with pulmonary hypertension due to left heart disease.

Sotatercept has previously been granted Breakthrough Therapy Designation and Orphan Drug designation by FDA, as well as Priority Medicines designation and Orphan Drug designation by the European Medicines Agency.

“Based on the profound improvements across primary and secondary outcome measures in the phase 3 STELLAR trial, we believe sotatercept has the potential to transform the treatment of patients with PAH,” Koglin said.¹ “We look forward to working closely with the FDA to bring sotatercept to patients in need.”

In an interview with HCPLive at ACC 2023, presenting investigator Marius M. Hoeper, MD, Hannover Medical School, described the 40-meter improvement from baseline the 6-minute walk distance as due to improvement in sotatercept-treated patients, rather than deterioration in the placebo group.²

He noted the safety data have not yet been alarming, despite increased hemoglobin levels, telangiectasia, and epistaxis observed in the sotatercept arm, but clinicians should remain vigilant with sotatercept treatment.

“We expect that patients are going to be exposed to this drug for many years,” he said. “And of course, we need to be cautious and vigilant to make sure that this doesn’t develop into something more serious than what we see now.”

References

Merck receives priority review from FDA for new Biologics License Application For Sotatercept, an activin signaling inhibitor to treat adults with pulmonary arterial hypertension (PAH). Merck.com. September 28, 2023. Accessed September 28, 2023. https://www.merck.com/news/merck-receives-priority-review-from-fda-for-new-biologics-license-application-for-sotatercept-an-activin-signaling-inhibitor-to-treat-adults-with-pulmonary-arterial-hypertension-pah/.
Iapoce C. Marius Hoeper, MD: Insight into stellar trial investigating Sotatercept for pah. HCP Live. March 9, 2023. Accessed September 28, 2023. https://www.hcplive.com/view/marius-hoeper-md-insight-stellar-trial-sotatercept-pah.