Actelion to Start a Phase 3 Trial Evaluating Opsumit as Treatment for Children with PAH

Actelion will soon start a Phase 3 clinical trial to assess the effectiveness of Opsumit (macitentan) in delaying the progression of pulmonary arterial hypertension (PAH) in children and adolescents. The long-term trial, called TOMORROW (pediaTric use Of Macitentan tO delay disease pRogRessiOn in PAH Worldwide), will be conducted in more than 20 countries and may lead to the first approved treatment for young PAH patients.

Opsumit, an orally available endothelin receptor antagonist (ERA), is currently approved in both Europe and the U.S. to treat progression in adults with PAH (WHO Group I in the U.S. and WHO Group II-III in Europe).

The TOMORROW study is a randomized, open-label and event-driven trial to examine the safety, efficacy, and pharmacokinetics of a pediatric formulation of Opsumit versus standard of care in young PAH patients. The drug, in a pediatric formulation, is a water-dispersible tablet with no taste, available in 0.5 mg, 2.5 mg and 5.0 mg doses. The trial’s primary efficacy endpoint is the time to the first Clinical Event Committee-confirmed outcome event, including clinical worsening of PAH, hospitalization due to PAH, atrial septostomy or Pott’s anastomosis, and it is expected to run for six years, with children being enrolled until 187 endpoints or measures of treatment effectiveness have been recorded.

“We take our leadership in PAH as a responsibility and have now committed to the first long-term, event-driven study in children with PAH using a pediatric formulation of macitentan. The design of the TOMORROW clinical trial allows the safe and comprehensive assessment of children over a long period of time,” Jean-Paul Clozel, MD, chief executive officer of Actelion, said in a press release.

TOMORROW will eventually involve children ages 1 month to 18 years, but will begin by establishing pharmacokinetic profiles in 40 PAH patients ages 2 to 18 years old, so that researchers can determine the best doses for younger patients. Once the dose is established, children under age 2 will be enrolled, and all patients randomly assigned to treatment either with Opsumit or with standard of care according to local practice.

“Clinical studies in children come with big challenges, such as the influence of growth stage and body weight on the dosage scheme and on potential side effects. PAH is a rare disease in adults and even more so in children, so pediatric PAH physicians have to mostly rely on research data collected in adults when weighing up treatment options for their younger patients,” said Maurice Beghetti, head of Paediatric Cardiology at the University Hospital of Geneva. “There is a significant medical need for showing the benefit of adequately adapted formulations and doses of PAH-specific medications in order to provide children with PAH with the most appropriate treatment.”

Because the trial is open-label, or unblinded in the choice of treatment among patients and trial researchers, members of the study’s Clinical Event Committee will be blinded in evaluating the results of its primary endpoints.

“As there is no globally approved treatment for PAH in children, it was not possible to define a single unique treatment as reference drug or standard background. The design of the TOMORROW study will ensure that children receive the best available standard of care therapy or macitentan, a treatment that is well supported by long-term efficacy and safety data in adults. … I welcome Actelion’s effort to broaden the pediatric knowledge base, which will help both physicians and their young PAH patients in the long term,” said Dunbar Ivy, director of the Pediatric Pulmonary Hypertension Program at Children’s Hospital Colorado.

PAH is a chronic, life-threatening disorder that severely compromises the function of the lungs and heart.