Riociguat deemed suitable for PAH in connective tissue disease

SAN FRANCISCO – Phase III clinical trial experience in using riociguat indicates that the drug is just as safe and effective in treating pulmonary arterial hypertension associated with connective tissue disease (CTD), particularly systemic sclerosis, as it is for the overall group of patients with PAH caused by various conditions.

“Riociguat [Adempas] slowed deterioration of exercise capacity in patients with scleroderma, with clinical effects sustained over the 2-year follow-up. Long-term safety and tolerability of riociguat in patients with PAH-CTD was quite acceptable and was similar to the overall PATENT population, with no new safety signals,” lead investigator Dr. Christopher P. Denton said at the annual meeting of the American College of Rheumatology.

Dr. Christopher P. Denton

The phase III, randomized, placebo-controlled PATENT-1 trial demonstrated riociguat’s benefits over 12 weeks, principally the increased exercise capacity in terms of 6-minute walk distance. The open-label extension PATENT-2 trial confirmed the long-term nature of the improvements out to 2 years. The trials were pivotal in securing approval of the novel soluble guanylate cyclase stimulator for treatment of PAH.

PAH-CTD cases comprised 25% of the total PATENT population, second only to patients with idiopathic disease. About half of the PAH-CTD cases were patients with systemic sclerosis (SSc), who typically have an especially poor prognosis. This offered the opportunity to fine-tune the analysis of riociguat’s efficacy and safety to this subgroup.

All PAH-CTD patients had appreciable signs of pulmonary hypertension on physical exertion. Most were already receiving PAH therapy, so any improvements would be on top of already existing treatment-related gains. At week 12 of the PATENT-1 trial, more PAH-CTD patients in the placebo group had died, worsened clinically, or withdrawn than in the riociguat group (24% vs. 8%). Clinical worsening had occurred in 12% of those receiving placebo, compared with none in the riociguat group. The benefits of riociguat in terms of 6-minute walk distance performance and improved World Health Organization functional class were especially pronounced for SSc patients. Analysis of PATENT-2 data demonstrated the durability of the improvements over the 2-year follow-up.

The types and frequencies of adverse events and serious adverse events were similar in PAH-CTD patients and the overall population. “Very reassuringly,” the 2-year survival rate exceeded 90% overall and was 93% in PAH-CTD patients and 94% in PAH patients with SSc, said Dr. Denton of University College London.

“The results are consistent with what is emerging from long-term trials and registry analyses, with an improvement in the longer-term outcome of patients with CTD- and SSc-associated PAH, which is likely a reflection of the more intense approach we are taking in the utility of drugs used in combination to target different pathogenic pathways,” Dr. Denton said.

Dr. Denton reported financial disclosures involving research funding with Actelion, Novartis, Roche, CSL Behring, and Bayer Healthcare. Bayer markets riociguat and sponsored the trials.