AMBITION: Combination therapy reduced risk for clinical failure in patients with PAH

In patients with pulmonary arterial hypertension, first-line therapy with a combination of ambrisentan and tadalafil reduced the risk for clinical failure compared with monotherapy with either drug, according to findings presented at ERS International Congress 2014.

Nazzareno Galié, MD, and colleagues conducted the randomized controlled AMBITION study to determine whether the ambrisentan/tadalafil combination was superior to ambrisentan (Letairis, Gilead Sciences) or tadalafil alone in treatment-naive patients with PAH (n=500).

Patients were randomly assigned on a 2:1:1 basis to combination therapy, ambrisentan monotherapy or tadalafil monotherapy. Mean treatment duration was 78.6 weeks for the combination therapy group, 66.6 weeks for the ambrisentan group and 71.6 weeks for the tadalafil group.

The primary endpoint was time to clinical failure, defined as a composite of death, hospitalization due to worsening PAH, disease progression or unsatisfactory long-term clinical response.

Galié, from the department of experimental, diagnostic and specialty medicine at the University of Bologna, Italy, and colleagues found that compared with pooled results from the monotherapy groups, the combination therapy group experienced a reduced risk for the primary endpoint (HR=0.502; 95% CI, 0.348-0.724).

They also observed that the risk reduction associated with the combination therapy was superior to that of either monotherapy individually (P<.01), and that the main treatment effect was driven by hospitalizations. According to a press release, the time to first hospitalization was delayed by 63% (HR=0.372; 95% CI, 0.217-0.639) in the combination therapy group.

According to the researchers, there were similar rates of adverse events leading to study drug discontinuation and serious adverse events in all groups, with the following events more common in the combination therapy group: peripheral edema, headache, nasal congestion and anemia.

“The AMBITION results … potentially establish a new treatment paradigm in PAH,” investigator Lewis J. Rubin, MD, emeritus professor at the University of California, San Diego, said in the press release.

According to the release, Gilead plans to submit the AMBITION data in a supplemental New Drug Application to the FDA by the end of the year. Ambrisentan/tadalafil combination therapy is not currently approved for treatment of PAH.

For more information:

Galié N. Abstract #2916. Presented at: ERS International Congress 2014; Sept. 6-10, 2014; Munich.

Disclosure: The study was cosponsored by Gilead Sciences and GlaxoSmithKline; Eli Lilly supplied additional funding and the tadalafil drug supply. Galié reports financial ties with Actelion, Bayer-Schering, Eli Lilly, GlaxoSmithKline, Novartis and Pfizer.