Opsumit (macitentan) is an oral medication developed by Actelion Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) to treat pulmonary arterial hypertension (PAH).

PAH is characterized by abnormally high blood pressure in the blood vessels carrying blood to the lungs. This is caused by the blood vessel narrowing and increasing resistance to blood flow, leading to high pressure. PAH is a serious complication that can occur in people with systemic scleroderma.

How Opsumit works

Endothelin-1 is one of the molecules that cause narrowing of blood vessels. Endothelin receptor antagonists, such as Opsumit, work by blocking endothelin’s binding partner and results in the widening of the blood vessels and reduction in blood pressure.

While there is no cure for PAH, Opsumit can improve symptoms and slow disease progression.

Opsumit in clinical trials

A Phase 3 clinical trial (NCT00660179) called The SERAPHIN study compared the effect of two doses of Opsumit and placebo in 742 patients 12 and older with PAH due to a wide variety of conditions,  including scleroderma. The participants were divided into three groups. Those in the first group received 3 mg and those in the second group received 10 mg of Opsumit once a day for one-and-a-half to two years. Those in the third group received a placebo.

The results showed that 10 mg of Opsumit reduced the risk of symptoms worsening, the need for prostanoid treatment (a type of PAH treatment), lung transplant, atrial septostomy (a heart operation), or death, by 45 percent compared to placebo, while 3 mg of Opsumit reduced these risks by 30 percent.

Ten mg of Opsumit also reduced the risk of hospitalization by half, while 3 mg of the medication reduced that risk by 34 percent.

Patients who received either dose of Opsumit also walked farther in the 6-minute walk test, a test measuring exercise capacity in people with chronic lung or heart conditions.

Opsumit was well-tolerated, but patients receiving 10 mg or 3 mg of the medication had lower red blood cell counts (4.3 and 1.7 percent, respectively) compared to those who received placebos (0.4 percent).

The study was completed in 2012, and the results were published in the New England Journal of Medicine.

An open-label extension of the SERAPHIN trial (NCT00667823) looked into the long-term safety of Opsumit and found it did not interact with PDE-5 inhibitors (another type of medication often used to treat PAH), and PDE-5 inhibitors did not significantly alter levels of Opsumit in the body. Higher concentrations of Opsumit resulted in lower resistance and blood pressures in the blood vessels of the lungs.

Actelion also is conducting an open-label Phase 3 clinical trial (NCT02932410) testing Opsumit in children ages 2 to 18 with PAH caused by a range of conditions, including scleroderma. There is no data on the safe use of Opsumit in children. Patients will receive either Opsumit, or standard treatment. Researchers will assess patients for worsening symptoms, the number of hospitalizations, the need for heart surgery or lung transplant, and death. This study is currently recruiting at 89 locations worldwide and plans to enroll 300 patients. It began in November 2017 and is scheduled to end in 2022.

Actelion also is carrying out an open-label Phase 4 clinical trial (NCT02310672) investigating the effects of 10 mg of Opsumit on heart function in patients with PAH. However, this trial is limited to those with idiopathic, inherited, drug-induced, or congenital heart defects related to PAH.  Patients will receive the medication for a year and will undergo right heart catheterization with a heart biopsy and heart MRIs at various intervals during the trial period. The study is currently recruiting participants at 50 locations worldwide. It began in 2015 and is scheduled to end in May 2019.

Another open-label Phase 4 study (NCT02968901) sponsored by Actelion looks to determine the effects of 10 mg of Opsumit plus 40 mg of Adcirca (tadalafil) (another PAH medication) in patients with PAH due to several conditions, including scleroderma. Patients will be assessed based on changes in lung blood vessel resistance, along with other markers of disease severity. Having begun in 2015, the study is expected to be completed in 2020. It is recruiting participants at several sites in France.

More details about Opsumit

Women using Opsumit should take extra precautions to avoid getting pregnant, as the medication confers a risk of serious birth defects. The FDA has required Opsumit to have a risk evaluation and mitigation strategy (REMS), a women-only program whose primary objectives are to educate healthcare providers, pharmacists, and patients regarding the safe use and risks of birth defects of Opsumit, and to reduce the incidence of Opsumit-induced birth defects.

One of the stipulations of this program requires all women of reproductive age to undergo monthly pregnancy tests while taking Opsumit. Opsumit can be dispensed only from certified pharmacies.

Common side effects that may occur while taking Opsumit include a stuffy nose, sore throat, airway irritation (bronchitis), headache, flu-like symptoms (fever, chills, body aches), and urinary tract infections.

Actelion is currently seeking expanded FDA approval for Opsumit to treat patients with chronic thromboembolic pulmonary hypertension who are not fit for surgery.

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