United Therapeutics Corporation (NASDAQ: UTHR) has announced the significant results of its long-term pivotal phase 3 Advance Outcomes study, demonstrating the efficacy of its once-daily oral prostacyclin, ralinepag, in treating patients with pulmonary arterial hypertension (PAH).
The study showed that ralinepag achieved a 55% reduction in the risk of a clinical worsening event compared to the placebo, with a hazard ratio of 0.45 and a highly statistically significant p-value of less than 0.0001. Notably, 80% of patients were on dual background therapy, and 70% were considered World Health Organization (WHO)/New York Heart Association (NYHA) functional class (FC) II at baseline.
In addition to meeting its primary endpoint, the study also demonstrated statistically significant improvements in secondary endpoints. Ralinepag increased the odds of achieving clinical improvement by 47% from baseline to week 28, as measured by the six-minute walk distance (6MWD) and change in n-terminal pro-b-type natriuretic peptide (NT-proBNP).
The benefits of ralinepag were consistent across all patient subgroups, including time since diagnosis, disease etiology, baseline 6MWD, and use of background therapies, indicating the broad therapeutic relevance of the treatment.
Furthermore, the safety profile of ralinepag was consistent with known prostacyclin-related adverse events, with no new safety signals observed. These results have prompted United Therapeutics to intend to submit a new drug application (NDA) for ralinepag to the U.S. Food and Drug Administration (FDA) by the second half of 2026.
Dr. Vallerie V. McLaughlin, the Kim A. Eagle MD Endowed Professor of Cardiovascular Medicine and Director of the Pulmonary Hypertension Program at the University of Michigan, expressed the significance of ralinepag's potency and once-daily oral dosing in real-world settings, highlighting its potential to delay disease progression in patients with PAH facing significant disease burden at baseline.
Martine Rothblatt, Ph.D., Chairperson, and Chief Executive Officer of United Therapeutics, emphasized the company's commitment to bringing transformative therapies to people living with PAH. She expressed optimism that ralinepag could improve long-term outcomes and potentially usher in a new era of treatment for PAH, addressing the profound unmet needs in the disease.
Derek Solum, Ph.D., Senior Director of Product Development at United Therapeutics, underscored the significance of ralinepag's extended-release profile and pharmacokinetic characteristics, which mimic the steady-state exposure of parenteral therapy, providing disease-mitigating capabilities that target underlying PAH pathology.
Ralinepag, a highly selective and potent prostacyclin (IP) receptor agonist, has the potential to redefine the PAH treatment landscape as the first and only once-daily oral prostacyclin, combining potent receptor affinity with continuous exposure to deliver long-term, durable efficacy and disease-mitigating outcomes.
The results of the Advance Outcomes study are expected to be presented at an upcoming international conference, and United Therapeutics plans to host a webcast to discuss the study results in detail.
PAH is a life-threatening disease characterized by increased pressure in the pulmonary arteries, affecting around 500,000 individuals worldwide, with approximately 50,000 affected individuals in the United States. United Therapeutics, as a public benefit corporation, is dedicated to transforming the treatment of rare diseases and pioneering alternatives to expand the supply of transplantable organs.
The company's commitment to advancing prostacyclin-based science and its potential to bring transformative therapies to patients living with PAH are reflected in the significant findings of the Advance Outcomes study, reinforcing its dedication to addressing the unmet needs in the treatment of PAH. Following these announcements, the company's shares moved -1.5%, and are now trading at a price of $464.93. For the full picture, make sure to review UNITED THERAPEUTICS Corp's 8-K report.
