OpsumitTreatment for Pulmonary Hypertension
Actelion Announces acceptance of the New Drug Application for macitentan by the US Food and Drug Administration
ALLSCHWIL/BASEL, SWITZERLAND - 14 December 2012 - Actelion (SIX: ATLN) today announced that the Food and Drug Administration (FDA) in the United States (US) has officially accepted the New Drug Application (NDA) for macitentan (Opsumit®).
On the 19th October Actelion submitted the NDA dossier for macitentan (Opsumit®) for the treatment of patients with pulmonary arterial hypertension to the US FDA. The review period is expected to last 12 months from the date of NDA submission.
Macitentan, a novel dual endothelin receptor antagonist, was studied in the pivotal, long-term, event-driven Phase III outcome study, SERAPHIN, in which 742 patients suffering from pulmonary arterial hypertension were randomized to receive either placebo or macitentan at 3 mg or 10 mg once daily. Treatment with macitentan has demonstrated a reduction in the risk of morbidity and mortality event over the treatment period versus placebo. This risk was reduced by 45 percent for patients in the 10 mg dose group (p<0.0001). The observed risk reduction was 30 percent (p=0.0108) for patients receiving the 3 mg dose. Patients in SERAPHIN were treated for up to three and a half years, and the most common adverse events associated with the use of macitentan were nasopharyngitis, headache and anemia.
Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion commented: "We are very happy that this very large dossier was accepted by the FDA and that we are another step closer to our goal of bringing this drug to patients with this life threatening disease."
About macitentan (Opsumit®)
Macitentan (Opsumit®) is a novel dual endothelin receptor antagonist (ERA) that resulted from a tailored drug discovery process with the target to develop an ERA optimized for efficacy and safety . Macitentan has a number of potentially key beneficial characteristics i.e., increased in vivo preclinical efficacy vs. existing ERAs resulting from sustained receptor binding  and physicochemical properties that allow an enhanced penetration into tissue . The clinical pharmacology program indicated a low propensity of macitentan for drug-drug interactions [5,6,7]
About macitentan (Opsumit®) submissions to healthcare authorities
On 22nd October 2012 Actelion announced that it had submitted a new drug application to the US Food and Drug Administration (FDA) seeking approval for macitentan (Opsumit®) in patients with pulmonary arterial hypertension.
On 22nd November 2012 Actelion announced that it had successfully submitted the Market Authorisation Application to the European Medicines Agency (EMA) and a validation letter had been received.
About the SERAPHIN study
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 . The pivotal Phase III study was designed to evaluate the efficacy and safety of macitentan (Opsumit®) - 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 enrollment 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 and Latin America, Europe, Asia-Pacific and Africa and was completed in the first half of 2012, with 287 patients having an adjudicated event.
About Pulmonary Arterial Hypertension
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 3 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.
Despite these advances in PAH, survival rates are unacceptably low and PAH remains incurable.
Senior Vice President, Head of Investor Relations & Public Affairs
Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil
+41 61 565 62 62
+1 650 624 69 36
Posted: December 2012
- Actelion submits a New Drug Application to the FDA for macitentan (Opsumit) for the treatment of patients with pulmonary arterial hypertension - October 22, 2012