Actelion’s Opsumit Approved by FDA for Pulmonary Arterial Hypertension

Actelion's opsumit approved by FDA
The FDA has recently approved the endothelin receptor antagonist, Opsumit, for clinical use to treat pulmonary arterial hypertension

 The Food and Drug Administration (FDA) issued a press statement on Oct. 18, 2013, approving the use of Opsumit for treatment of pulmonary arterial hypertension (PAH). Opsumit, whose generic name is Macitentan, is a novel drug developed by the pharmaceutical and biotechnology company Actelion.

Actelion was founded in Dec. 1996 by a group of Swiss scientists, and is currently managed by Chief Executive Officer Jean-Paul Clozel, a French cardiologist. Clozel’s company soared to success after development of Tracleer (bosentan), which was also administered for treatment of pulmonary arterial hypertension; revenue for the drug, in 2005 alone, exceeded $480 million.

Clozel, meanwhile, argues his company’s success was propelled by the Swiss biotech environment:

“I really don’t think Actelion could have become what it is in another country… We’re based in Basel, where we border three countries and where a third of the population makes its living from the drug industry. There’s a lot of international expertise here.”

Actelion’s Opsumit Drug

Opsumit is defined as an endothelin receptor antagonist, which blocks endothelin receptors, helping to relax the pulmonary arteries. In turn, this helps to decrease the blood pressure within the vessels that supply deoxygenated blood to the lungs.

The orally administered drug is actually an improvement of Tracleer; according to Reuters, however, the drug is due to lose its patent protection in 2015.

Opsumit was extensively tested, back in August, during the SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome) phase three trial. The results, which were published in the New England Journal of Medicine, demonstrated significant reduction in the morbidity and mortality in patients with symptomatic pulmonary arterial hypertension, who had been prescribed a two year treatment plan of Opsumit. The best results were witnessed in those patients who were assigned 10mg/day of Opsumit, whilst less tangible benefits were evident in those subjects assigned a daily dose of 3mg.

Opsumit was found to delay clinical worsening and death from pulmonary arterial hypertension, and also reduced the number of recorded hospitalizations. Dr. Richard Channick, Director of Pulmonary Hypertension and Thromboendarterectomy Program, of Massachusetts General Hospital, recently elaborated on the SERAPHIN clinical trials:

The drug comes with a Boxed Warning highlighting the drug’s unsuitability for clinical use in pregnant females, since it is capable of causing permanent damage to the developing fetus.

According to the FDA’s latest statement, the drug can also cause a number of common side effects, including a reduction in red blood cell count, cold-like symptoms, sore throat, headache, flu, bronchitis and urinary tract infections.

Meanwhile, according to Actelion’s website, the drug’s efficacy in treating other medical pathologies is currently being investigated:

“Macitentan is currently investigated in a pivotal Phase III program in patients with ischemic digital ulcers associated with systemic sclerosis, initiated in December 2011. Additionally, following excellent preclinical results, a Phase I/Ib open-label study was initiated with macitentan in patients with recurring glioblastoma.”

Pulmonary Arterial Hypertension

Actelion’s Opsumit is designed to treat chronic pulmonary arterial hypertension, resulting in an increase in blood pressure within the lung vasculature. Based upon the World Health Organization (WHO) classification, several factors are thought to contribute towards the disease, including drugs, genetics, infection collagen vascular diseases and other cardiovascular pathologies.

Regardless of the initial cause, pulmonary arterial hypertension entails vasoconstriction of the blood vessels that supply deoxygenated blood to the lung tissue. This narrowing makes it harder for the heart to pump blood through the vessels of the lungs, which begin to harden over time. Ultimately, as the right ventricle contracts more forcefully to ensure the lung tissue is adequately perfused, the right side of the heart becomes hypertrophic, essentially causing it to enlarge.

A hypertrophic right ventricle can eventually lead to right-sided heart failure, reducing the volume of oxygenated blood that arrives at the left ventricle from the lungs. This has a knock-on impact when the left ventricle tries to pump oxygenated blood to the remainder of the body, which struggles to fulfill this role during periods of strenuous physical exertion.

Pathophysiology of pulmonary arterial hypertension treated with opsumit
Diagram showing the pathophysiological issues seen in a typical PAH patient, including hypertrophy, narrowing of the arteries, fibrosis, development of pulmonary blood clots and dysfunction of the right ventricle.

As a result, the following characteristic symptoms are observed in patients afflicted with the condition:

  • Shortness of breath
  • Fatigue
  • Cough
  • Fainting
  • Swelling of ankles and feet (peripheral edema)

PAH is an incurable, chronic disease that reduces life expectancy significantly and imposes serious lifestyle restrictions upon sufferers. The American Lung Association states that 50 percent of PAH sufferers die within five years of early diagnosis; without treatment, this period is lessened to three years.

Director of the Pulmonary Hypertension Program in the Division of Cardiovascular Medicine at the University of Michigan, Dr. Vallerie McLaughlin, boasted about the implications of their new drug:

“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.”

Now that Actelion’s Opsumit drug has been approved by the FDA for pulmonary arterial hypertension, the treatment is slated to be available to U.S. patients in November.

By: James Fenner

Actelion Press Release

FDA Press Release

New England Journal of Medicine Source

American Lung Association



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