Ralinepag to strengthen United Therapeutics’ PAH portfolio

Pulmonary Arterial Hypertension Highlights

30 May, 2022 | DelveInsight

  • Ralinepag, a next-generation, orally available, non-prostanoid selective prostacyclin receptor agonist significantly reduced PVR compared with placebo in patients with moderately symptomatic PAH
  • The overall safety profile of Ralinepag was similar to that reported in a parent study (APD811-003) completed in June 2017 demonstrating the benefit-risk ratio of Ralinepag as unchanged and positive

Pulmonary arterial hypertension (PAH) is a rare lung disease characterized by debilitating symptoms such as dyspnoea on exertion, fainting, and clinical symptoms of heart failure. PAH is characterized by pulmonary vascular remodelling, resulting in increased pulmonary vascular resistance. Defective transforming growth factor-β and bone morphogenetic protein signalling are associated with PAHs. According to DelveInsight’s epidemiology analysis for PAH, there were nearly 69,605 prevalent cases in the 7MM [the US, EU-5 (Germany, France, Italy, Spain, and the UK), and Japan] in the year 2021. The estimations suggest a rise in cases in future years.

New therapies that target these underlying mechanisms of vascular remodelling are needed to slow the onset and progression of the disease.

On this note, DelveInsight analyzed the discussions around the PAH intervention presented at the American Thoracic Society (ATS) International Conference 2022 wherein United Therapeutics manifested the role of Ralinepag that will revolutionize the future treatment pattern of PAH by addressing the unmet needs and improving the patients' outcome in PAH.

Ralinepag is in development to treat World Health Organization (WHO) Group 1 PH. Ralinepag is a next-generation, orally available, non-prostanoid, selective, and potent IP agonist which has been studied in human pulmonary tissues. In vitro studies indicate that Ralinepag has high binding affinity and selectivity at the human IP receptor. Ralinepag is formulated as an oral, extended-release tablet taken once daily.

The study presented at the ATS 2022 was a Phase II open-label extension (OLE) study to evaluate the long-term safety and tolerability of Ralinepag in subjects with PAH. Secondary objectives evaluated changes from baseline in 6-minute walk distance (6MWD), WHO Functional Class (FC), hemodynamics, and time to clinical worsening. Subjects who completed the 22-week placebo-controlled APD811-003 study (NCT02279160) (parent study) were eligible to participate in the OLE study APD811-007 (NCT02279745). All subjects received open-label treatment with oral Ralinepag. Subjects who received a placebo in the parent study underwent an individualized dose titration period while those on Ralinepag started treatment in the OLE study at their current dose. Dose and titration adjustments were based on subject tolerability and Investigator discretion. Subjects had on-site clinical assessments every 3 months until they discontinued or transitioned to the Phase III OLE study at study termination.

Out of the 61 subjects randomized to the parent study, 45 transitioned to the OLE study. Most subjects (86.7%) were less than 65 years of age, where 86.7% were female, 93.3% were White, and 71.1% were in WHO FC II at baseline. Overall, subjects had a total median treatment duration of 153.4 weeks from the start of the OLE study to study closure. Overall, subjects experienced significant improvements in the median change from the OLE baseline in 6MWD at Months 3 (20.9 m), 6 (17.6 m), 12 (28.5 m), 24 (41.0 m), and 36 (47.0 m) suggesting treatment durability. Notable improvements from the OLE baseline were observed in median pulmonary vascular resistance (-52.2 dyn.sec/cm5) and mean pulmonary arterial pressure (-2.0 mmHg). PVR reductions reported for the Ralinepag group in the parent study were maintained in the OLE, while subjects from the placebo group saw significant improvements once on active treatment in the OLE. There were no clinically relevant changes in the time to the clinical worsening of WHO FC. Adverse events (AEs) in the OLE were consistent with the known safety profile of prostacyclin therapies, with headache (64%), diarrhea (38%), and jaw pain (33%) reported most commonly. Overall, 11.1% of subjects were discontinued due to AEs.

The overall safety profile of Ralinepag was similar to that reported in the parent study and data from the OLE study demonstrated the benefit-risk ratio of Ralinepag as unchanged and positive. According to DelveInsight’s analysis, Ralinepag is expected to enter the market in the year 2024 for the treatment of patients affected with PAH and it is anticipated to gain a significant share in the market after launch.

Extensive due diligence on Ralinepag has been conducted over time, applying two decades of knowledge about PAH. On receiving FDA approval via at least one of its several different potential regulatory pathways to success, Ralinepag is expected to help greater than 10,000 patients annually over the next decade, reinforcing United’s existing portfolio of PAH therapies.

For a more detailed analysis of Pulmonary Arterial Hypertension visit at: Pulmonary Arterial Hypertension market

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