Opsumit: Withdrawal of the application to change the marketing authorisation

Opsumit is a medicine used for the long-term treatment of pulmonary arterial hypertension (PAH), in which abnormally high blood pressure in the lungs leads to symptoms such as breathlessness and fatigue. If left untreated PAH can result in weakening of the heart muscle or heart failure.

Opsumit has been authorised in the EU since December 2013. It contains the active substance macitentan and is available as tablets.

The company applied to extend the use of Opsumit to treat CTEPH which is similar to PAH but has a different cause (mainly blood clots).

Opsumit was expected to be used for patients with CTEPH that cannot be corrected by surgery and that causes undue symptoms such as breathlessness or chest pain when the patient carries out normal physical activities (WHO functional classes II and III).

The active substance in Opsumit, macitentan, works by blocking receptors in the blood vessels which are the targets for endothelin, a substance naturally produced in the body. When endothelin attaches to these receptors it triggers a narrowing of the blood vessels walls and increases the blood pressure. By blocking these receptors in the lungs, macitentan helps stop this effect, widening the blood vessels in the lungs and thereby bringing down the blood pressure. 

Opsumit was expected to work in patients with CTEPH in the same way that it works in patients with PAH.

The company presented data from a main study involving 80 patients with CTEPH that could not be corrected with surgery in which the patients were given either Opsumit or placebo (a dummy treatment). The study looked at improvements in pulmonary vascular resistance (PVR) after four months. PVR is a measure of how hard the heart has to work to push blood through the blood vessels in the lungs.

The application was withdrawn after the European Medicines Agency had evaluated the initial information from the company and had prepared questions for the company. After the Agency had assessed the company’s responses to the questions, there were still some unresolved issues.

Based on the review of the information and the company’s responses to the Agency’s questions, at the time of the withdrawal, the Agency had some concerns and its provisional opinion was that Opsumit could not have been authorised for the treatment of CTEPH.

The results of the main study were difficult to interpret, and there were several deviations from the study protocol which may have made the results less reliable. Therefore, at the time of the withdrawal, the Agency’s opinion was that the company had not provided enough information to support the application for a change to the marketing authorisation of Opsumit.

In its letter notifying the Agency of the withdrawal of application , the company stated that it had withdrawn the application following feedback from EMA’s human medicines committee (CHMP) about the study and the way it was carried out.

The company informed the Agency that it does not anticipate any consequences on ongoing clinical trials with Opsumit. If you are in a clinical trial and need more information about your treatment, speak with your clinical trial doctor.

There are no consequences on the use of Opsumit in its currently authorised use.