Adcirca (tadalafil) is an approved therapy to reduce the symptoms of pulmonary arterial hypertension (PAH) and increase the exercise ability of patients. Adcirca was developed originally by Eli Lilly, which holds the marketing rights to the product in Europe. United Therapeutics holds the license to produce and market Adcirca in the U.S.

Tadalafil also is marketed under the brand name Cialis to treat erectile dysfunction and benign prostatic hypertrophy.

How Adcirca works

PAH is associated with a narrowing of the blood vessels (vasoconstriction) in the lungs, leading to high blood pressure and an inability to effectively transport oxygen around the body due to reduced blood flow. One cause of this is low levels of a molecule called cGMP, which is involved in the relaxation of the smooth muscles of the artery walls. 

Adcirca is an inhibitor of the enzyme phosphodiesterase-5 (PDE-5) that normally drives the breakdown of cGMP. Blocking PDE-5 means that cGMP is not cleared as quickly, resulting in an increase in cGMP. Higher levels of cGMP relax the smooth muscles of the arteries, leading to vasodilation and a reduction of blood pressure. This improves the transport of oxygen around the body, which can improve the patient’s ability to exercise.

Adcirca in clinical trials

The main clinical trial that demonstrated the safety and effectiveness of Adcirca as a PAH treatment was the PHIRST-1 trial (NCT00125918). This randomized, double-blind, placebo-controlled Phase 3 study, investigated how effectively Adcirca improved a patient’s ability to exercise at one of four different doses, compared to a placebo. The main outcome was the change in the distance the patient could walk in six minutes after 16 weeks of treatment. A total of 406 patients were enrolled at sites in the U.S., France, and Italy.

The results of PHIRST-1 were published in the scientific journal Circulation. They showed that Adcirca improved the exercise capacity of patients in a dose-dependent manner and the highest dose of 40 mg significantly improved the distance walked in six minutes

This trial was followed by a 52-week extension study, PHIRST-2 (NCT00549302), to assess the long-term safety and potential benefit of the treatment. A total of 357 patients were enrolled to receive either a 20 mg or 40 mg dose of Adcirca daily.

The results, published in the Journal of the American College of Cardiology, suggested that Adcirca was associated with an improved time to PAH symptom-worsening. Improvements seen with the high dose of Adcirca in the six-minute walk test were maintained in the extension study. Patients who were switched from the placebo or low doses of Adcirca at the start of PHIRST-2 to the high dose showed improvements, but not to the same extent as patients who initially were given 20 mg or 40 mg of Adcirca in PHIRST-1.

Eli Lilly is investigating the safety and effectiveness of Adcirca in PAH patients who are younger than 18 in a Phase 3 clinical trial (NCT01824290) at 50 sites worldwide. The randomized, double-blind trial aims to recruit 134 participants to be given either Adcirca or a placebo for six months. Patients also will be given the option to enroll in a two-year extension study.

Adcirca has been assessed in multiple other clinical trials, including in combination with other medication. For example, Actelion is running a Phase 4 open-label trial (NCT02968901) that is recruiting participants with newly diagnosed PAH in France to assess Adcirca in combination with its PAH therapy Opsumit (macitentan).

Other information

The U.S. Food and Drug Administration (FDA) approved Adcirca for the treatment of PAH in May 2009. Adcirca was approved for marketing in the European Union in October 2008.

Common side effects associated with Adcirca are back pain, indigestion, headache, limb and muscle pain, nausea, and flushing.

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