- Phase III study TOMORROW aims to show the long-term benefits of macitentan (Opsumit®) in children with pulmonary arterial hypertension (PAH)
- Global program has received endorsement from the US FDA (through a pediatric Written Request) and in the EU (through a Paediatric Investigation Plan)
ALLSCHWIL/BASEL, SWITZERLAND – 06 July 2016 - Actelion Ltd (SIX: ATLN) announced today that it will be initiating a Phase III study to evaluate the effect of macitentan on delaying disease progression in children with PAH using a pediatric formulation of macitentan (Opsumit).
TOMORROW (pediaTric use Of Macitentan tO delay disease pRogRessiOn in PAH Worldwide) is a multicenter, controlled, randomized, open-label event-driven study to assess the efficacy, safety and pharmacokinetics of macitentan versus standard of care in children with PAH.
The study will enroll children between the age of 1 month and 18 years in more than 20 countries. Initially, only children aged between 2 and < 18 years will be enrolled, and pharmacokinetic profiles collected in the study for up to 40 patients will allow Actelion to determine the doses for younger patients. Once the dose is determined, the study protocol will be amended to include children below 2 years of age. The children will be randomized in a 1:1 ratio into two treatment groups – macitentan administered as a pediatric formulation or standard of care as per local practice. The pediatric formulation of macitentan is a round dispersible tablet that is neutral in taste. It is available in three different dose strengths, containing 0.5 mg, 2.5 mg and 5.0 mg macitentan. To make them easier for children to swallow, the tablets can be dispersed in water on a spoon.
The trial is expected to last up to 6 years, with children being enrolled until 187 primary efficiency endpoint events have occurred. The primary efficacy endpoint is defined as the time to the first Clinical Event Committee (CEC) confirmed outcome event.
Maurice Beghetti, Head of Pediatric Cardiology at the University Hospital of Geneva, commented: “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. 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. TOMORROW as a robust study assessing long-term treatment with the appropriate pediatric formulation of macitentan will deliver the sought-after data on all fronts.”
Dunbar Ivy, Director of the Pediatric Pulmonary Hypertension Program at Children’s Hospital Colorado, commented: “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. This will render the study ethical, informative, and feasible and 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.”
Jean-Paul Clozel, MD and CEO of Actelion, commented: “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. This is another example of our long-term commitment to the PAH community and our intention to broaden the use of macitentan to new patient populations.”