Respira Therapeutics has announced the dosing of the first patient in the United States in its Phase 2b VIPAH-PRN clinical trial of RT234, a novel inhaled therapy for pulmonary arterial hypertension (PAH). The trial marks a significant step toward developing the first "as needed" treatment option for PAH patients who experience episodic symptoms despite ongoing maintenance therapy.
RT234-PAH delivers vardenafil, a potent PDE5 inhibitor vasodilator, as a dry powder inhaled treatment administered via an Axial Oscillating Sphere dry powder inhaler. The multicenter study will evaluate the safety and preliminary efficacy of RT234 in acutely improving episodic symptoms and exercise capacity in patients with New York Heart Association (NYHA) Functional Class II-III symptoms.
Addressing a Critical Unmet Need in PAH Management
"The initiation of this clinical trial represents an important milestone for Respira and is a critical next step in potentially offering patients with PAH an acute treatment to manage their shortness of breath, which prevents them from performing normal daily duties," said Carol Satler, PhD, M.D., President and Chief Medical Officer of Respira.
PAH is a serious and progressive condition characterized by high blood pressure in the arteries of the lungs. Despite receiving standard maintenance therapies, many patients continue to experience debilitating episodes of shortness of breath, fatigue, and exercise intolerance that significantly impact their quality of life.
"People suffering from this debilitating and serious condition who are being treated with maintenance therapies still experience episodes of shortness of breath, tiredness and inability to exercise, and there are currently no rapid onset therapies available for 'as needed' use to mitigate these episodes," Dr. Satler explained.
Trial Design and Objectives
The VIPAH-PRN 2b trial (RT234-PAH-CL202) is structured as a dose-escalation study that will consist of two sequential cohorts receiving RT234 as single doses. The primary focus is to evaluate acute changes in symptoms following administration of RT234 in subjects with PAH.
Researchers hypothesize that inhaled RT234 may provide therapeutic benefit for acute use in patients with World Health Organization (WHO) Group 1 Pulmonary Hypertension by:
- Improving exercise capacity
- Enhancing performance in activities of daily living
- Reducing exertional symptoms such as dyspnea
- Mitigating negative impacts on quality of life
Raymond L. Benza, MD, Director of the Division of Cardiovascular Medicine at The Ohio State University Wexner Medical Center, emphasized the importance of this approach: "Enabling PAH patients to be more active is key to their physical and mental health. Now with the study of RT234, we are examining our ability to boost physical activity when a patient needs it. It's potentially a great step forward in our battle with this disease."
A First-in-Class Approach
RT234 represents a paradigm shift in PAH treatment. While all current PAH therapies are administered according to specific treatment regimens and monitored for chronic improvements, RT234 is designed for on-demand use to provide acute symptom relief when patients need it most.
The investigational therapy has already demonstrated significant safety margins in preclinical testing and was generally well tolerated in Phase 1 clinical studies, with pharmacokinetic properties consistent with expectations for an acute medication.
Importantly, Respira has received FDA Orphan Drug designation for vardenafil for the PAH indication. The active ingredient is already FDA-approved in oral form for a non-PAH indication, allowing the company to pursue the 505(b)(2) approval pathway. This regulatory strategy enables Respira to reference previous findings of safety and efficacy of vardenafil to supplement their data on the proprietary inhalation powder formulation.
Innovative Drug Delivery Approach
Respira's approach combines proprietary inhaled drug formulations with dry powder inhaler technology to enhance drug targeting to the small airways of the lung. This strategy aims to improve dose consistency while optimizing delivery to the lung periphery.
The company's technology potentially offers advantages over traditional oral medications by delivering the active compound directly to the site of action, potentially reducing systemic side effects while providing more rapid onset of action—a critical factor for an "as needed" therapy.
Future Directions
Beyond the current Phase 2b trial in PAH, Respira has indicated plans to pursue additional indications for RT234 in other WHO pulmonary hypertension patient groups. This suggests a broader potential application for their inhaled therapy approach across various forms of pulmonary hypertension.
For patients interested in learning more about the VIPAH-PRN 2b trial, information is available at clinicaltrials.gov or the dedicated study website at https://www.vipah-prntrials.com/.
