A combination therapy for pulmonary arterial hypertension (PAH) based on drugs from Gilead and GlaxoSmithKline has aced a phase IIIb/IV trial.
Ambrisentan is commercialised by Gilead in the US as Letairis and by GSK outside the US as Volibris, while tadalafil is promoted by GSK in Europe for PAH as Adcirca, under licence from Lilly.
Combining ambrisentan and tadalafil cut the risk of treatment failure by 50%, according to the AMBITION study, which compared the pair to each drug given alone.
The trial involved previously-untreated patients with World Health Organization (WHO) functional class II and III patients, who have mild to moderate limitations in physical activity as a result of PAH but are generally comfortable at rest.
PAH is a rare and progressive disorder, characterised by high blood pressure in pulmonary arteries that carry blood from the heart to the lungs that typically occurs when the arteries become narrow in diameter or get blocked.
The magnitude of the benefit in the trial was “impressive, particularly in WHO functional class II patients where we observed nearly an 80% reduction in risk of clinical failure versus monotherapy,” said Prof Lewis Rubin of the University of California, San Diego, who chaired the AMBITION steering committee.
The results – which have been published in the New England Journal of Medicine (NEJM) – answer a key question in the treatment of PAH, namely whether patients should be treated with more than one drug from the outset.
The results could give a boost to both drugs in the PAH market, particularly as they are facing competition from new entrants such as Actelion’s Opsumit (macitentan) and Uptravi (selexipag), Bayer’s Adempas (riociguat) and United Therapeutics Orenitram, an oral formulation of the long-standing injectable PAH treatment Remodulin (treprostinil).
A recent report from Transparency Market Research predicted that the PAH market will grow at around 2.3% a year to 2020, with revenues swelling from just over $4bn in 2013 to $5.2bn.
Uptravi and Adempas are expected to drive that growth, although the loss of patent protection for Actelion’s older drug Tracleer (bosentan) in some markets later this year will apply a brake on the market.