The US Food and Administration has cleared a new treatment approach for pulmonary arterial hypertension which combines Gilead’s Letairis and Lilly’s tadalafil to magnify the benefits offered by each therapy alone. 

Letairis is an endothelin receptor antagonist first approved in the US in 2007 as a monotherapy for PAH to improve exercise ability and delay clinical worsening. The drug is also sold as Volibris by GlaxoSmithKline outside of the US. 

Tadalafil is a PDE5 inhibitor cleared in 2009 to improve exercise ability in PAH patients and is marketed as Adcirca by United Therapeutics, which licensed PAH rights to the compound for PAH from Lilly.

Now, the drugs’ combination has been approved on the back of clinical data from the AMBITION trial showing that patients are less likely to experience disease progression or be hospitalised, and also more likely to experience improvement in exercise ability, than those receiving either effective therapy alone.

In the study, the combination therapy demonstrated superiority in reducing the risk of the composite primary endpoint - time to first occurrence of death, hospitalisation for worsening PAH or decreases in the six minute walk test - by 49% and 45% versus monotherapy with Letairis or tadalafil, respectively.

Combination therapy also cut the risk of hospitalisation for worsening PAH by 67% and 56% compared to Letairis or tadalafil, respectively, while patients also experienced statistically significant improvements from baseline in the six minute walking distance test versus individual monotherapy, with a median difference of 24 meters and 20 meters.

AMBITION was cosponsored by Gilead and GSK, but Lilly also provided funding and tadalafil drug supply for the trial.