Actelion Ltd today announced the approval of Opsumit (macitentan) 10 mg for the treatment of pulmonary arterial hypertension (PAH) by the Therapeutic Goods Administration (TGA) of Australia.

Opsumit Approved by SwissMedic for Pulmonary Arterial Hypertension

In Press Release by Cameron

Actelion Ltd today announced the approval of Opsumit (macitentan) 10 mg for the treatment of pulmonary arterial hypertension (PAH) by the Therapeutic Goods Administration (TGA) of Australia.

February 14, 2014

Actelion announced today that SwissMedic has approved Opsumit® (macitentan) for PAH patients within Switzerland.

Opsumit is indicated for the long-term treatment of pulmonary arterial hypertension (PAH) in patients of WHO Functional Class II to III to reduce morbidity and the risk of mortality.

Opsumit is effective when used as monotherapy or in combination with phosphodiesterase-5 inhibitors or inhaled / oral prostanoids.

Jean-Paul Clozel, Chief Executive Officer of Actelion commented; “The SwissMedic approval, as one of the reference health authorities, is another positive step for Actelion and Opsumit in the global approval process. We are very proud that the convincing data from the SERAPHIN study and the translation into a label today, means that patients with PAH here in Switzerland can be treated with Opsumit. We will cooperate with the Swiss authorities to ensure availability for patients in due course.”

The SwissMedic approval was based on data from the landmark Phase III SERAPHIN study. In the SERAPHIN study, treatment with macitentan 10 mg resulted in a 45% risk reduction (hazard ratio 0.55; 97.5% CI: 0.39 to 0.76; logrank p < 0.0001) of the composite morbidity-mortality endpoint when compared to placebo.

The most commonly reported adverse drug reactions are nasopharyngitis (14%), headache (14%) and anaemia (13%). The majority of adverse reactions are mild to moderate in intensity.


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.


SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) was the largest and longest randomized, controlled study in PAH patients to include a clearly defined morbidity/mortality primary endpoint [1]. The pivotal Phase III study was designed to evaluate the efficacy and safety of Opsumit (macitentan) – a novel dual endothelin receptor antagonist that resulted from a tailored drug discovery process – through the primary endpoint of time to first morbidity and all-cause mortality event in patients with symptomatic PAH.

Global enrolment was completed in December 2009 with a total of 742 patients. Patients were randomized 1:1:1 to receive two different doses of macitentan (3 mg and 10 mg once daily) or placebo. Patients were allowed to receive PAH background therapy throughout the study, either PDE-5 inhibitors or oral/inhaled prostanoids. This event-driven study was conducted in 151 centers from almost 40 countries in North America, Latin America, Europe, Asia-Pacific and Africa and was completed in the first half of 2012, with 287 patients having an adjudicated event.


Patients were randomized to placebo (n=250), macitentan 3 mg (n=250), or macitentan 10 mg (n=242). The primary end point occurred in 46.4%, 38.0%, and 31.4% of the patients in these groups, respectively. The hazard ratio for macitentan 3 mg versus placebo was 0.70 (97.5% CI, 0.52 to 0.96; p=0.0108) and the hazard ratio for macitentan 10 mg versus placebo was 0.55 (97.5% CI, 0.39 to 0.76; p<0.0001). Worsening of pulmonary arterial hypertension was the most frequent primary end point event. The effect of macitentan on this end point was observed irrespective of background therapy for pulmonary arterial hypertension.


The most commonly reported adverse drug reactions with Opsumit are nasopharyngitis (14.0%), headache (13.6%) and anaemia (13.2%).


The first approval globally of the new drug application for Opsumit (macitentan) was issued by the US Food and Drug Administration (FDA) on 18 October 2013 for the treatment of pulmonary arterial hypertension. Opsumit (macitentan) is also approved for PAH in the EU, Canada, and Australia. Regulatory reviews in other countries are ongoing.


Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of an affected individual. The symptoms of PAH are non-specific and can range from mild breathlessness and fatigue during normal daily activity to symptoms of right heart failure and severe restrictions on exercise capacity and ultimately reduced life expectancy.

PAH is one group within the classification of pulmonary hypertension (PH). This group includes idiopathic PAH, heritable PAH and PAH caused by factors which include connective tissue disease, HIV infection and congenital heart disease.

The last decade has seen significant advances in the understanding of the pathophysiology of PAH, which has been paralleled with developments of treatment guidelines and new therapies. Drugs targeting the three pathways that have been established in the pathogenesis of PAH are endothelin receptor antagonists (ERAs), prostacyclins and phosphodiesterase-5 inhibitors. PAH treatments have transformed the prognosis for PAH patients from symptomatic improvements in exercise tolerance 10 years ago to delayed disease progression today. Improved disease awareness and evidence-based guidelines developed from randomized controlled clinical trial data have highlighted the need for early intervention, goal-oriented treatment and combination therapy.

In PAH, survival rates are unacceptably low and PAH remains incurable.

Press release here.