Gilead Sciences and GlaxoSmithKline have caused a stir at the European Respiratory Society meeting in Munich with very impressive late-stage data on a first-line therapy that combines their pulmonary arterial hypertension treatments.

The combined treatment consists of ambrisentan - the PAH drug sold as Letairis by Gilead in the USA and Volibris by GSK elsewhere - and tadalafil, marketed as Adcirca by United Therapeutics which licensed the rights to the compound for PAH from Eli Lilly; it is the active ingredient in Lilly’s erectile dysfunction treatment Cialis. In the study, called AMBITION, the combo (ambrisentan 10mg and tadalafil 40mg) reduced the risk of clinical failure by 50% compared to the pooled ambrisentan and tadalafil monotherapy arm.

Statistically significant improvements were also observed for three secondary endpoints (six-minute walk distance test, percentage of patients with satisfactory clinical response and change from baseline in N-terminal pro-B-type natriuretic peptide). There was no difference with the other two secondary endpoints (WHO functional class and Borg dyspnea index), while rates of adverse events leading to discontinuation were similar across treatment arms. The study was co-sponsored by Gilead and GSK, while Lilly also provided funding and tadalafil drug supply.

Lewis Rubin of the University of California, San Diego and co-chair of the AMBITION steering committee, said that the majority of studies to date “have evaluated add-on combination treatment approaches with mixed results”. Now, having demonstrated a 50% reduction in risk of clinical failure, ambrisentan/tadalafil together as upfront combination therapy “potentially establish a new treatment paradigm in PAH”.

The other co-chair, Nazzareno Galie of the University of Bologna echoed that view, saying AMBITION represents “one of the most important steps forward in the treatment of patients with PAH”, adding that it could become the standard of care. The companies plan to submit the AMBITION data to regulators on both sides of the Atlantic in the next few months.

Despite the presence of GSK and Gilead, the biggest player in the PAH market is Actelion, with Tracleer  (bosentan). The latter will be going off-patent in the next couple of years but the Swiss biotech has already launched its follow-up, Opsumit (macitentan).