Actelion Ltd, a biopharmaceutical company, has received the United States Food and Drug Administration (FDA) approval for the use of orally available endothelin receptor antagonist Opsumit (macitentan) 10 mg once daily for the treatment of pulmonary arterial hypertension (PAH) to delay disease progression.
Opsumit is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression. Disease progression included: death, initiation of intravenous (IV) or subcutaneous prostanoids, or clinical worsening of PAH (decreased six-minute walk distance, worsened PAH symptoms and need for additional PAH treatment). Opsumit also reduced hospitalization for PAH.
Effectiveness was established in a long-term study in PAH patients with predominantly WHO Functional Class II-III symptoms treated for an average of two years. Patients were treated with Opsumit monotherapy or in combination with phosphodiesterase-5 inhibitors or inhaled prostanoids. Patients had idiopathic and heritable PAH (57 per cent), PAH caused by connective tissue disorders (31 per cent), and PAH caused by congenital heart disease with repaired shunts (eight per cent).
Dr Vallerie McLaughlin, director of the Pulmonary Hypertension Programme in the Division of Cardiovascular Medicine at the University of Michigan, commented: "Over the past twenty years, great strides have been made in treating PAH patients. However, there has been a medical need for innovative treatments that improve long-term outcomes. Opsumit is the first clinically proven and only oral treatment option indicated to delay disease progression and reduce the need for PAH hospitalization."
Dr McLaughlin concluded: "These effects were demonstrated in SERAPHIN, the first and largest PAH outcome study to date, where Opsumit was given on average for two years, as a monotherapy or in combination with phosphodiesterase-5 inhibitors or inhaled prostanoids. I am very pleased that PAH patients will have this new treatment option."
Jean-Paul Clozel, MD and chief executive officer of Actelion commented: "Today's approval of Opsumit by the FDA is providing the PAH community with a unique treatment option, the only oral PAH medicine that has proven to delay disease progression. Over the last 14 years, Actelion has worked tirelessly to first discover and then develop Opsumit in the largest, longest and first-ever outcome study in PAH. I would like to express my gratitude to all the members of the PAH community. Without their contribution, Opsumit would not have become a reality. We will now leverage our existing PAH expertise and infrastructure to bring Opsumit to patients within the coming weeks."
The US label for Opsumit carries a Boxed Warning alerting patients and health care professionals that the drug should not be used in pregnant women because it can harm the developing fetus. Female patients can receive the drug only through the Opsumit REMS Programme. All female patients must be enrolled in the programme, comply with pregnancy testing requirements and be counselled regarding the need for contraception.
Physicians are advised to measure hemoglobin and liver enzymes prior to initiation of Opsumit and repeat during treatment as clinically indicated.
In the United States, Actelion expects Opsumit to become available to patients in November. Outside of the United States, Actelion continues to work with health authorities to obtain regulatory approval for Opsumit.
The FDA approval was based in part on data from the landmark phase III SERAPHIN study. Published in the New England Journal of Medicine in August 2013, the SERAPHIN study showed the risk of the first occurrence of a morbidity or mortality event, the primary endpoint of the study, was reduced by 45 per cent (p<0.0001) with macitentan 10 mg compared to placebo. This effect was observed irrespective of whether or not patients were already treated with other therapies for PAH. SERAPHIN also showed a risk reduction in PAH related hospitalization and death of 50 per cent (p<0.0001) compared to placebo.
Pulmonary arterial hypertension is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of an affected individual.
Opsumit (macitentan) is a novel dual endothelin receptor antagonist (ERA) that resulted from a tailored drug discovery process with the target of developing an ERA to address efficacy and safety.