Real Clinical Data Supports Volibris’ Efficacy, Safety to Treat PAH in Japanese Population

Alice Melão, MSc avatar

by Alice Melão, MSc |

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Interim data collected from a Japanese clinical setting demonstrates the post-marketing efficacy and safety of Volibris (Letairis, ambrisentan) for the treatment of patients with pulmonary arterial hypertension (PAH).

Oral administration of the drug improved the mean pulmonary arterial pressure and pulmonary vascular resistance with a good safety profile.

The results were reported in the study, “Surveillance on The Safety and Efficacy of Ambrisentan (Volibris Tablet 2.5 mg) in Patients with Pulmonary Arterial Hypertension in Real Clinical Practice: Post-marketing Surveillance (Interim Analysis Report),” published in the journal Clinical Drug Investigation, and add further clinical evidence of the therapeutic potential of Volibris.

Ambrisentan is a highly selective inhibitor of the endothelin isoform type A (ETA) receptor, which is known to mediate the vasoconstrictive and proliferative effects of the cell-signaling protein endothelin-1. Approved in the U.S. since 2007, ambrisentan is marketed in the United States by Gilead under the brand name Letairis and by GlaxoSmithKline as Volibris in Europe and other countries.

In Japan, Volibris has received temporary approval due to limited information on the effects of the drug on the Japanese population. Despite the extensive clinical data demonstrating the safety and efficacy of Volibris, only one open study (NCT00540436) was conducted in 25 Japanese PAH patients.

The ongoing post-marketing surveillance study (NCT01406327) was designed to evaluate the incidence of adverse events in Japanese people with PAH treated with Volibris based on prescribing recommendations in general clinical practice.

To date, the research team has evaluated data collected from 702 PAH patients ages 15 or older from 214 clinical sites. Of these 702 patients, 77.8% had PAH at WHO functional class II or III. The patients were followed for a mean time of 392.7 days after starting Volibris treatment.

Efficacy data showed significant improvements in mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac output (CO) after one year of treatment. Preliminary analysis of the six-minute walk distance test (6MWD; assesses exercise capacity) in 62 patients also showed improvements from baseline of about 15 meters.

These positive effects on PAH were further demonstrated by a positive change by at least one grade in the WHO classification in 21% and 22.3% of the patients reported after six and 12 months, respectively, of treatment with Volibris.

The safety profile of the drug was found to be similar to previous reports, with a total of 324 adverse drug reactions reported in 29.1% of patients.

The most common adverse side effects were anemia (4.6%), peripheral swelling due to fluid accumulation (4.1%), headache (3.6%), fluid retention (2.6%), abnormal hepatic function (2.3%), and nosebleeds (2.1%).

Eleven patients were found to develop interstitial lung disease (ILD). However, these cases could not be linked directly to the administration of the drug, since these patients also had secondary diseases that could contribute to ILD development.

“The interim results showed safety consistent with the known profile of ambrisentan in terms of the types and frequencies of [adverse reactions] in patients with PAH in real clinical practice, in comparison with previous clinical trials in Japan and the rest of the world,” researchers concluded.

“These results provided another corroboration of the tolerability of ambrisentan, and we continue to monitor proper use information via the post-marketing surveillance to ensure any new safety signals are identified in a timely manner,” the researchers added.

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