Actelion Pharmaceuticals has received a complete response letter from the U.S. Food and Drug Administration (FDA) specifying that the company needs to conduct further studies and obtain more data in order to accurately assess the use of Opsumit (macitentan) in the treatment of patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).
The letter is in response to Actelion’s submission in April 2018 of a supplemental New Drug Application (sNDA) for Opsumit. A complete response letter from the FDA indicates that the agency has finished reviewing the submission application of a new or generic drug, and has decided that the drug will not be granted approval for marketing in its current form.
“We will work closely with the FDA to review the information outlined in their letter and gain a full understanding of next steps. We are committed to making a difference in the lives of people living with pulmonary hypertension and CTEPH,” Martin Fitchet, MD, Actelion’s global head of research and development, said in a press release.
CTEPH is a complication of pulmonary embolism (sudden blockage of major blood vessels in the lungs), and a significant cause of chronic PH that leads to increased pulmonary vascular resistance, right heart failure, and death.
Opsumit is an orally active endothelin receptor antagonist (ERA) that works by reducing the levels of a substance called endothelin in the blood. Endothelin is present in very high levels in patients with PH, and plays an important role in constricting (narrowing) blood vessels.
The medication was designed to improve pulmonary vascular resistance, and exercise capacity in PH patients. The oral therapy is approved for the treatment of pulmonary arterial hypertension, as it helps ease the disease symptoms, and slows down disease progression.
In the 24-week Phase 2 MERIT-1 clinical trial (NCT02021292), researchers tested whether 10 mg of Opsumit would be efficacious, safe, and tolerable for patients with inoperable CTEPH. Results showed that the use of Opsumit significantly improved the patient’s pulmonary vascular resistance and exercise capacity, and was well-tolerated.
Results from the trial were published in 2017 in the journal The Lancet Respiratory Medicine, in an article titled “Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study.”
Based on these positive results, in April 2018, Actelion submitted an sNDA to the FDA seeking expanded approval for Opsumit to treat inoperable CTEPH (WHO Group 4), to which the FDA has now replied with a complete response letter.
In August 2018, Actelion also filed a request with the European Medicines Agency for expanded approval of Opsumit as a treatment for adults with moderate to severe inoperable CTEPH. If approved, Opsumit will become the first ERA-based therapy available in the European Union for inoperable CTEPH treatment.