United Therapeutics has linked a once-daily drug candidate to a 55% drop in the risk of clinical worsening in a phase 3 trial, setting the company up to seek FDA approval in pulmonary arterial hypertension (PAH) this year.
The drugmaker randomized 687 people with PAH to receive ralinepag or placebo in addition to standard background therapy. The primary endpoint looked at the time to the first clinical worsening, a term that captured outcomes including death, PAH hospitalizations and disease progression. Ralinepag cut the risk of clinical worsening by 55% versus placebo, achieving the trial’s primary endpoint.
United CEO Martine Rothblatt, Ph.D., said on a call with investors that the outcome is better than the results of any other trial of a prostacyclin or a pill. Pointing to ralinepag’s daily oral dosing and durability, Rothblatt said the data support the prompt use of the molecule as a first-line treatment.
United saw (PDF) worsening events in 18.3% of patients on ralinepag, compared to 35.9% of their peers on placebo. The rates of death and PAH hospitalization were similar in the treatment and control arms. But fewer people receiving ralinepag had disease progression, started inhaled or infused prostacyclin or suffered an unsatisfactory long-term clinical response, driving the primary endpoint hit.
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The company also reported significant improvements on secondary endpoints, including six-minute walk distance and the change in a heart disease biomarker. Ralinepag increased the odds of achieving clinical improvement by 47% from baseline to Week 28. United said the changes were consistent across all subgroups, a finding Rothblatt said suggests ralinepag will be given to tens of thousands of patients.
United plans to file for FDA approval by the second half of the year. The company has predicted once-daily dosing will position ralinepag favorably compared to Uptravi, Johnson & Johnson’s twice-daily PAH drug. J&J reported Uptravi sales of $1.9 billion last year. Rothblatt said on the call that the prospect of Uptravi losing patent protection is “completely irrelevant” to ralinepag because United has much better data than J&J does.