EMA has recommended granting a marketing authorisation in the European Union (EU) for Winrevair (sotatercept) to treat adult patients with pulmonary arterial hypertension (PAH), in combination with other specific PAH therapies, to improve exercise capacity.
Pulmonary arterial hypertension is a rare, long-term, debilitating and life-threatening condition in which patients have abnormally high blood pressure in the arteries in the lungs. Many patients experience breathing difficulty that limits their physical activity. Despite approved therapies, long-term prognosis remains poor: it is estimated that around 50% of patients will die within five to seven years after diagnosis.
Winrevair (sotatercept) is the first activin signalling inhibitor therapy approved to treat PAH. In the body, proteins called activins attach to a receptor called ActRIIA to stimulate the growth of cells that make up the blood vessels. These receptors are over-active in patients with PAH. Sotatercept is a copy of ActRIIA, and because it also attaches to activins, it prevents them from activating the receptor. In this way, sotatercept regulates the growth of new blood vessel cells in the lungs. This leads to reduced narrowing and thickening of the blood vessels, thus improving the symptoms of the disease.
The medicine is administered once every 3 weeks as a single injection under the skin and may be administered by patients or caregivers with guidance, training and follow-up from a healthcare provider.
The recommendation is based on the results of a randomised, double-blind, placebo-controlled, multicentre clinical trial that evaluated the efficacy and safety of sotatercept in 323 adults with PAH on stable treatment for more than 90 days with background PAH therapy (monotherapy or combination therapy).
Results of the trial show that patients on sotatercept had significantly improved exercise capacity measured by how far they were able to walk within six minutes at the start of treatment and after 24 weeks. This increase is considered clinically relevant as it compares to the results of the pivotal study of already-authorised products for PAH.
The most common side effects associated with this medicine are headache, nose bleeds, rash, tiny blood vessels that look like pink or red lines on the skin (telangiectasia), diarrhoea, dizziness and redness. Although Winrevair is generally well tolerated, there have been rare reports of serious side effects affecting the blood, such as increased blood pressure, low platelet count (thrombocytopenia) which can increase the risk of bleeding, and increased haemoglobin concentrations which can lead to thromboembolic events such as a stroke. The last two conditions listed are considered manageable by modifying the dose of Winrevair.
Winrevair was supported through EMA's PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients' unmet medical needs.
The opinion adopted by the CHMP is an intermediary step on Winrevair’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.
Notes
1. The applicant for Winrevair is Merck Sharp & Dohme B.V.
2. Winrevair was granted eligibility to PRIME on 30 April 2020 for the treatment of treatment of pulmonary arterial hypertension.
3. Winrevair was designated as an orphan medicinal product on 9 December 2020 for the treatment of treatment of pulmonary arterial hypertension. Following this positive CHMP opinion, the Committee for Orphan Medicinal Products (COMP) will assess whether the orphan designations should be maintained.