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Actelion set to launch macitentan for pulmonary arterial hypertension

Macitentan, for the treatment of pulmonary arterial hypertension (PAH), will soon be available in the UK. The drug, to be marketed by Actelion as Opsumit, has been developed by structurally modifying the company’s existing PAH medicine bosentan to improve efficacy and safety.

PAH is a condition characterised by raised blood pressure in the arteries that supply the lungs, which can lead to heart failure. Macitentan is indicated as monotherapy, or in combination, for the long-term treatment of adult patients who have PAH of World Health Organization functional class II or III (see Panel 1).

Macitentan is an endothelin receptor antagonist that has been shown to bind to pulmonary arterial smooth muscle cells with high affinity, which helps to prevent vasoconstriction and smooth muscle cell proliferation.

Neil Hamilton, principal pharmacist at Sheffield Teaching Hospitals NHS Foundation Trust, said that macitentan provides an alternative to the currently prescribed endothelin receptor antagonists bosentan and ambrisentan.

Macitentan provides an alternative to the currently prescribed endothelin receptor antagonists bosentan and ambrisentan.

Neil Hamilton

The effectiveness of macitentan was assessed in a double-blind phase III study sponsored and analysed by Actelion. Patients were given a once-daily dose of macitentan 3mg (n=250) or macitentan 10mg (n=242) or placebo (n=250) for a median duration of 115 weeks. The primary endpoint was time to first occurrence of a morbidity or mortality event, up to the end of double-blind treatment. The events included were death, atrial septostomy, lung transplantation, or initiation of intravenous or subcutaneous prostanoids or worsening of PAH.

In patients who received macitentan 10mg, there was a 45 per cent reduction in the relative risk of experiencing the morbidity and mortality primary endpoint compared with placebo (hazard ratio 0.55, 97.5 per cent confidence interval 0.39–0.76; P<0.0001). The absolute risk reduction was 16 per cent. When risk of all-cause death alone was analysed, the relative risk reduction for macitentan compared with placebo was not significant (HR 0.64, CI 0.29–1.42; P=0.2).

Dr Hamilton said that it was unfortunate that there were no head-to-headstudies with drugs currently in use. The design of the study (using a morbidity and mortality endpoint) made efficacy comparisons with existing treatment options difficult.

However, he pointed out that the levels of oedema and liver function test abnormalities for patients taking macitentan were the same as for placebo patients. This is a good thing, Dr Hamilton explained, because this can be an issue in this class of medicine. “I expect it to be prescribed as a second-line oral therapy: either in addition to or instead of a phosphodiesterase-5 inhibitor, most commonly sildenafil.”

The most commonly reported adverse effects of the medicine are nasopharyngitis, anaemia, bronchitis and headache, according to the summary of product characteristics, which notes that most adverse effects are mild or moderate. Macitentan is contraindicated during pregnancy and in women of childbearing potential who are not using reliable contraception.

Actelion told PJ Online that it expects macitentan to be available in the UK by the end of February 2014.

Panel 1: World Health Organization functional classification

Class I: Patients with pulmonary hypertension (PH) but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnoea or fatigue, chest pain, or near syncope.

Class II: Patients with PH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnoea or fatigue, chest pain, or near syncope

Class III: Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnoea or fatigue, chest pain, or near syncope.

Class IV: Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure. Dyspnoea or fatigue, or both, may even be present at rest. Discomfort is increased by any physical activity.

Product details

Action: Orally active endothelin receptor antagonist, active on both ETA and ETBreceptors.

Dose: 10mg once-daily at the same time each day with water.

Legal category: POM

NHS List price: Actelion is currently negotiating a price for the medicine with the Department of Health.

  • This article was updated on 7 January 2014 to correct an error in the description of the drug’s mechanism of action and to include a comment from Neil Hamilton.


Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.11132488

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