From GSK:

GSK receives CHMP positive opinion to expand indication for Volibris® in pulmonary arterial hypertension

23 October 2015

GSK today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for a variation to expand the current therapeutic indication for Volibris® (ambrisentan) to include its use in combination treatment for patients with pulmonary arterial hypertension (PAH).

“Today’s decision represents an important milestone for the PAH community, supporting the potential for initial combination treatment in this highly debilitating and limiting disease”, said Jonathan Langley, Clinical Investigation Lead PAH, GSK Rare Diseases. “If approved, this could help improve clinical outcomes for patients across Europe suffering from this rare condition. We look forward to receiving a final decision from the European Commission in the coming months.”

This positive opinion was based on data from the Phase 3b/4 AMBITION study, the first and only outcomes study to compare the efficacy and safety of investigational first-line combination therapy of ambrisentan and tadalafil to first-line monotherapy of either treatment alone in treatment-naïve patients with PAH. The study was recently published in the New England Journal of Medicine and showed that the combination of ambrisentan and tadalafil reduced the risk of clinical failure by 50% in treatment-naïve PAH patients compared to pooled ambrisentan and tadalafil monotherapy (p=<.001)1. AMBITION was co-sponsored by GSK and Gilead, with support provided by Eli Lilly.

The positive opinion is a formal recommendation by the CHMP to expand the existing marketing authorisation for ambrisentan to include combination treatment. A final decision from the European Commission is anticipated by December 2015.

Further regulatory submissions to include the AMBITION data in the ambrisentan label are ongoing and planned in other countries.

About Ambrisentan

Ambrisentan, a selective endothelin type-A receptor antagonist, is approved in the EU and other countries as a once-daily treatment for PAH, (WHO Group 1) in patients with WHO/NYHA functional class II and III symptoms. GSK commercialises ambrisentan under the tradename Volibris® in territories outside of the United States and Gilead commercialises ambrisentan under the tradename Letairis® in the U.S. Ambrisentan has been granted orphan drug status for the treatment of PAH in Australia, Europe, Japan, Korea and United States.

For the approved indication and EU summary of product characteristics for ambrisentan, please visit www.ema.europa.eu.

Letairis and Volibris are registered trademarks of Gilead Sciences, Inc or one of its related companies.

About Pulmonary Arterial Hypertension (WHO Group 1)

PAH is a debilitating disease characterised by constriction of the blood vessels in the lungs leading to high pulmonary arterial pressures. These high pressures make it difficult for the heart to pump blood through the lungs to be oxygenated. Patients with PAH suffer from shortness of breath as the heart struggles to pump against these high pressures, causing such patients to ultimately die of heart failure.  PAH can occur with no known underlying cause, or it can occur secondary to diseases such as

connective tissue disease, congenital heart defects, cirrhosis of the liver and HIV infection2. PAH afflicts approximately 200,000 patients worldwide3.

Important Safety Information for ambrisentan in the European Union

The following Important Safety Information is based on a summary of the Summary of Product Characteristics for ambrisentan. Please consult the full Summary of Product Characteristics for all the labelled safety information for ambrisentan.

Ambrisentan (Volibris®)

Ambrisentan is contraindicated in patients with hypersensitivity to the active substance, to soya or any of the excipients.

Ambrisentan is contraindicated in pregnancy. Animal studies have shown that ambrisentan is teratogenic. There is no experience in humans. Women receiving ambrisentan must be advised of the risk of foetal harm and alternative therapy initiated if pregnancy occurs. It is not known whether ambrisentan is excreted in human breast milk. The excretion of ambrisentan in milk has not been studied in animals. Therefore breast-feeding is contraindicated in patients taking ambrisentan.

In males, the development of testicular tubular atrophy in male animals has been linked to the chronic administration of endothelin receptor antagonists (ERAs), including ambrisentan. Ambrisentan has not been studied in a sufficient number of patients to establish the benefit/risk balance in WHO functional class I PAH.

Liver function abnormalities have been associated with PAH. Cases consistent with autoimmune hepatitis, including possible exacerbation of underlying autoimmune hepatitis, hepatic injury and hepatic enzyme elevations potentially related to therapy have been observed with ambrisentan. Therefore hepatic aminotransferases (ALT and AST) should be evaluated prior to initiation of ambrisentan and treatment should not be initiated in patients with baseline values of ALT and/or AST>3xULN.

Peripheral oedema, fluid retention and headache (including sinus headache, migraine) were the most common adverse reactions observed with ambrisentan.

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