FDA News

FDA approves use of combination therapy for treatment of PAH

Gilead Sciences, Inc. announced that the FDA has approved the use of a combination of an endothelin receptor antagonist and a PDE5 inhibitor for patients with peripheral arterial hypertension to reduce disease progression and hospitalization for worsening pulmonary arterial hypertension and to improve exercise ability, according to a press release.

The approval is for the use of ambrisentan (Letairis, Gilead Sciences, Inc.) in conjunction with tadalafil. Use is indicated for patients with WHO Group 1 pulmonary arterial hypertension (PAH). Combination of the two medications represents a new treatment strategy for patients with PAH.

“Based on the data supporting today’s approval, we now know that patients receiving ambrisentan and tadalafil up front are less likely to experience disease progression or be hospitalized, and have more improvement in exercise ability than patients receiving either effective therapy alone. As such, this combination represents a new treatment strategy for patients living with this debilitating and life-threatening disease,” Ronald J. Oudiz, MD, professor of medicine at David Geffen School of Medicine at UCLA and director of the Liu Center for Pulmonary Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, said in the release.

Approval was supported by data from the AMBITION study. Patients with WHO functional class II or III PAH were randomly assigned to receive once-daily ambrisentan 5 mg plus tadalafil 20 mg (n = 302), ambrisentan monotherapy (n = 152) or tadalafil monotherapy (n = 151). If tolerated, the tadalafil dose was increased to 40 mg at 4 weeks and the ambrisentan dose was increased to 10 mg at 8 weeks. The primary endpoint was time to first occurrence of death, hospitalization for worsening PAH and 6-minute walk distance combined with WHO functional class III or IV symptoms sustained over 14 days, or reduction in 6-minute walk distance sustained over 14 days combined with WHO functional class III or IV symptoms sustained over 6 months. Results showed that 20% of patients assigned combination therapy experienced the primary endpoint compared with 35% of patients assigned ambrisentan monotherapy and 30% assigned tadalafil monotherapy, according to the release. Combination therapy was also associated with reduced risk for hospitalization for worsening PAH and improvement in 6-minute walk distance.

Disclosure: Oudiz reports receiving grant support from Ikaria and Janssen, and grant support/personal fees from Actelion, Bayer, Gilead, Lung Biotech, Pfizer, Reata and United Therapeutics outside the submitted work.

Gilead Sciences, Inc. announced that the FDA has approved the use of a combination of an endothelin receptor antagonist and a PDE5 inhibitor for patients with peripheral arterial hypertension to reduce disease progression and hospitalization for worsening pulmonary arterial hypertension and to improve exercise ability, according to a press release.

The approval is for the use of ambrisentan (Letairis, Gilead Sciences, Inc.) in conjunction with tadalafil. Use is indicated for patients with WHO Group 1 pulmonary arterial hypertension (PAH). Combination of the two medications represents a new treatment strategy for patients with PAH.

“Based on the data supporting today’s approval, we now know that patients receiving ambrisentan and tadalafil up front are less likely to experience disease progression or be hospitalized, and have more improvement in exercise ability than patients receiving either effective therapy alone. As such, this combination represents a new treatment strategy for patients living with this debilitating and life-threatening disease,” Ronald J. Oudiz, MD, professor of medicine at David Geffen School of Medicine at UCLA and director of the Liu Center for Pulmonary Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, said in the release.

Approval was supported by data from the AMBITION study. Patients with WHO functional class II or III PAH were randomly assigned to receive once-daily ambrisentan 5 mg plus tadalafil 20 mg (n = 302), ambrisentan monotherapy (n = 152) or tadalafil monotherapy (n = 151). If tolerated, the tadalafil dose was increased to 40 mg at 4 weeks and the ambrisentan dose was increased to 10 mg at 8 weeks. The primary endpoint was time to first occurrence of death, hospitalization for worsening PAH and 6-minute walk distance combined with WHO functional class III or IV symptoms sustained over 14 days, or reduction in 6-minute walk distance sustained over 14 days combined with WHO functional class III or IV symptoms sustained over 6 months. Results showed that 20% of patients assigned combination therapy experienced the primary endpoint compared with 35% of patients assigned ambrisentan monotherapy and 30% assigned tadalafil monotherapy, according to the release. Combination therapy was also associated with reduced risk for hospitalization for worsening PAH and improvement in 6-minute walk distance.

Disclosure: Oudiz reports receiving grant support from Ikaria and Janssen, and grant support/personal fees from Actelion, Bayer, Gilead, Lung Biotech, Pfizer, Reata and United Therapeutics outside the submitted work.