Corsair Pharma Receives Positive FDA Feedback on TRX-248 Transdermal System Development for Pulmonary Arterial Hypertension
Corsair Pharma, Inc., a private, clinical-stage biopharmaceutical company focused on developing innovative prodrug-based transdermal medicines to improve the delivery and therapeutic profiles of established treatments, has announced a positive outcome from its pre-investigational new drug (pre-IND) meeting with the U.S. Food and Drug Administration (FDA) for its investigational TRX-248 Transdermal System. The product is a once-daily treprostinil prodrug patch being developed for the treatment of pulmonary arterial hypertension (PAH).
The FDA’s feedback followed its review of Corsair’s pre-IND submission, which included summary results from the company’s initial Phase 1 pharmacokinetic (PK) study. According to Corsair, the regulatory agency provided feedback supporting the company’s proposed development pathway and offered guidance regarding its planned registration strategy.
The company intends to pursue regulatory approval for TRX-248 through the FDA’s 505(b)(2) regulatory pathway. This approach is expected to allow Corsair to rely, in part, on the agency’s previous findings of safety and effectiveness for Remodulin®, an established treprostinil therapy used in patients with PAH.
As part of its regulatory strategy, Corsair plans to establish a scientific bridge between TRX-248 and subcutaneous Remodulin by demonstrating bioequivalence based on systemic treprostinil exposure. The proposed development program is designed to establish that the investigational transdermal system can deliver treprostinil exposure comparable to the approved reference product while offering a different and potentially more convenient administration method.
Bobby Singh, M.Pharm., Ph.D., President and Chief Operating Officer of Corsair Pharma, expressed satisfaction with the outcome of the FDA meeting, noting that the feedback supports the company’s planned bioequivalence-based 505(b)(2) development strategy.
According to Singh, Corsair has begun preparations for a pilot bioequivalence study, which the company expects to initiate in early 2027. Results from this U.S.-based study are expected to provide important information for determining the final design of a pivotal bioequivalence study.
The company anticipates initiating the pivotal study in late 2027, with topline data expected by the middle of 2028. These studies are expected to represent important milestones in advancing TRX-248 toward potential regulatory submission and commercialization.
Corsair believes its transdermal delivery technology could address certain limitations associated with existing treprostinil administration methods and provide patients with a more flexible treatment option.
George Mahaffey, Chief Executive Officer of Corsair Pharma, highlighted that although treprostinil is an established treatment for PAH, the administration requirements associated with currently available formulations can create challenges for patients and limit treatment flexibility.
He stated that TRX-248 has the potential to address some of these challenges by providing a convenient once-daily patch-based approach. Following encouraging Phase 1 findings, the company is preparing to submit its investigational new drug (IND) application and continue discussions with the FDA as the program advances through clinical development.
TRX-248 Transdermal System Designed to Improve Treprostinil Delivery
TRX-248 is being developed as a transdermal prostacyclin therapy intended to deliver treprostinil through the skin using a proprietary prodrug-based formulation.
The investigational product is designed around TRX-248, an inactive or pharmacologically inert prodrug that can cross the skin and subsequently be converted into active treprostinil after absorption.
This approach is intended to provide a controlled and continuous delivery of treprostinil over a 24-hour period through a single daily patch application.
Unlike administration methods that require infusion pumps, needles, or inhalation devices, the TRX-248 Transdermal System is designed to deliver the active medication through the skin without requiring an external drug delivery pump.
The company describes TRX-248 as the only clinical-stage transdermal prostacyclin currently in development.
The product’s development is based on the potential advantages of combining an established therapeutic molecule with a new drug delivery approach. By modifying how treprostinil enters the body, Corsair aims to improve the treatment experience while maintaining systemic exposure to the active drug.
The company believes that a once-daily transdermal formulation could provide an alternative for patients who may find existing administration methods challenging.
Another important feature of the system is its intended flexibility in dosing. Corsair is developing multiple patch sizes to support straightforward dose titration. This approach is expected to allow healthcare professionals to adjust treatment according to individual patient requirements while maintaining a convenient daily administration schedule.
The system is also designed to provide steady treprostinil exposure throughout the day, potentially avoiding some of the practical challenges associated with other delivery approaches.
Understanding Pulmonary Arterial Hypertension and the Role of Treprostinil
Pulmonary arterial hypertension is a progressive and potentially life-threatening condition characterized by increased blood pressure in the pulmonary arteries, the blood vessels responsible for transporting blood from the heart to the lungs.
The disease involves narrowing, remodeling, and dysfunction of the pulmonary arteries, which increases resistance to blood flow through the lungs.
As pulmonary vascular resistance increases, the right side of the heart must work harder to pump blood through the pulmonary circulation. Over time, this additional workload can lead to right ventricular enlargement, impaired cardiac function, and potentially right-sided heart failure.
Patients with PAH may experience symptoms such as shortness of breath, fatigue, chest discomfort, dizziness, and reduced exercise capacity. As the disease progresses, these symptoms can significantly affect daily activities and quality of life.
Although treatment options have advanced, PAH remains a chronic condition requiring ongoing medical management and monitoring.
Treprostinil is an established prostacyclin therapy used in the management of PAH. It acts through prostacyclin-related pathways to promote vasodilation and inhibit platelet aggregation, helping reduce pulmonary vascular resistance.
Treprostinil-based therapies can be administered through different delivery methods, including subcutaneous infusion, intravenous infusion, and inhalation, depending on the formulation and approved product.
While these approaches provide important treatment options, their administration requirements may create practical challenges for certain patients.
For example, infusion-based treatments may require patients to manage pumps, infusion equipment, and administration sites. These requirements can affect convenience, daily routines, and treatment flexibility.
Inhaled therapies also involve specific administration procedures that patients must follow regularly.
Corsair is developing TRX-248 to explore whether transdermal delivery can provide another approach to administering treprostinil while maintaining the systemic exposure necessary for therapeutic activity.
Positive FDA Pre-IND Meeting Supports the 505(b)(2) Regulatory Strategy
The positive outcome of Corsair’s pre-IND meeting represents an important regulatory milestone for the TRX-248 development program.
During the meeting process, the FDA reviewed information submitted by the company, including the initial Phase 1 pharmacokinetic findings and the proposed clinical and regulatory development strategy.
The feedback provided by the agency supported Corsair’s planned approach to pursuing approval through the 505(b)(2) pathway.
The 505(b)(2) regulatory pathway is designed to allow certain drug applications to rely, at least in part, on information that the FDA has already determined regarding the safety and effectiveness of an approved reference drug.
For TRX-248, Corsair intends to use the FDA’s previous findings for Remodulin as part of its regulatory foundation.
Remodulin is an approved treprostinil product used in PAH. By establishing an appropriate scientific bridge between the investigational transdermal system and subcutaneous Remodulin, Corsair aims to support its proposed regulatory strategy through comparative pharmacokinetic evidence.
The planned approach will focus on demonstrating bioequivalence based on systemic treprostinil exposure.
Bioequivalence assessments generally compare the rate and extent to which the active drug becomes available in the systemic circulation following administration of different formulations or delivery systems.
For TRX-248, the objective is to demonstrate that the transdermal prodrug system can achieve systemic treprostinil exposure comparable to the reference product.
This strategy could potentially reduce the need to repeat certain aspects of clinical development already established for the approved drug, subject to FDA requirements and the evidence generated through the proposed studies.
Although the agency’s feedback supports the proposed pathway, the company will still need to complete the required development activities and demonstrate that its product satisfies applicable regulatory standards before approval can be considered.
Phase 1 Study Demonstrates Continuous Treprostinil Exposure
Corsair’s regulatory discussions were supported by results from its completed Phase 1 pharmacokinetic study in healthy volunteers.
The study evaluated the initial performance of the TRX-248 Transdermal System, including systemic treprostinil exposure, pharmacokinetic characteristics, safety, and tolerability.
According to the company, the investigational patch demonstrated the ability to provide steady and continuous treprostinil levels during a 24-hour application period.
This finding supports the intended design of the product as a once-daily transdermal delivery system.
Continuous drug exposure is an important consideration for PAH therapies because maintaining appropriate therapeutic drug levels is central to the ongoing management of the disease.
The Phase 1 findings also demonstrated a favorable safety and tolerability profile, according to Corsair.
These preliminary results provide an initial clinical foundation for advancing the product into additional studies designed to evaluate its pharmacokinetic comparability with subcutaneous Remodulin.
The company believes the findings support further investigation of the prodrug-based delivery platform and its potential to provide a differentiated approach to established PAH treatment.
However, Phase 1 studies in healthy volunteers are generally designed to assess early safety and pharmacokinetic characteristics rather than establish therapeutic effectiveness in patients.
Consequently, additional clinical studies will be necessary to determine whether TRX-248 can achieve the intended drug exposure and demonstrate an acceptable safety profile in the context of its proposed use.
Pilot Bioequivalence Study Expected to Begin in Early 2027
Following the FDA meeting, Corsair has initiated preparations for a pilot bioequivalence study of the TRX-248 Transdermal System.
The company expects this U.S.-based study to begin in early 2027.
The pilot study is intended to generate comparative pharmacokinetic data that will help evaluate systemic treprostinil exposure following administration of the transdermal patch compared with subcutaneous Remodulin.
The results are expected to inform the final design of a subsequent pivotal bioequivalence study.
The pilot study will therefore play an important role in refining the company’s clinical development strategy, including the design and execution of the larger study planned for late 2027.
Bioequivalence studies are particularly important for development programs that rely on an approved reference drug under the 505(b)(2) pathway.
By demonstrating comparable systemic exposure, Corsair aims to establish the scientific connection required to support reliance on the existing safety and effectiveness findings associated with Remodulin.
The company expects the pilot study to provide the information needed to determine the appropriate design and parameters for the pivotal evaluation.
Pivotal Bioequivalence Study Planned for Late 2027
Corsair anticipates initiating its pivotal bioequivalence study in late 2027, following completion and evaluation of the pilot study.
The pivotal study is expected to provide the principal comparative pharmacokinetic evidence supporting the proposed regulatory strategy for TRX-248.
The company plans to evaluate systemic treprostinil exposure from the investigational transdermal system against subcutaneous Remodulin.
Successful demonstration of bioequivalence would represent an important milestone in advancing the program through the planned 505(b)(2) regulatory pathway.
Corsair currently expects data from the pivotal study by the middle of 2028.
The results are expected to guide subsequent regulatory planning and determine the next steps toward a potential marketing application.
The company will also continue engaging with the FDA throughout the development process to address regulatory expectations and ensure that the proposed clinical program aligns with the agency’s requirements.
While the development timeline reflects the company’s current expectations, actual milestones will depend on study initiation, enrollment, execution, data analysis, and regulatory considerations.
Proprietary Prodrug Technology Supported by Intellectual Property Protection
An important component of the TRX-248 program is its proprietary prodrug molecule.
Corsair stated that TRX-248 is protected by an issued composition-of-matter patent and additional intellectual property protections.
The proprietary molecule is designed to cross the skin in its inactive prodrug form before being converted into active treprostinil after absorption.
This delivery strategy is intended to combine the therapeutic properties of an established prostacyclin with a differentiated transdermal administration platform.
The company’s approach focuses on improving drug delivery rather than developing an entirely new active therapeutic mechanism.
This strategy may offer development advantages by building on the established clinical experience associated with treprostinil while investigating a different route of administration.
The intellectual property portfolio is also expected to support the company’s efforts to develop and potentially commercialize the product, subject to successful clinical development and regulatory approval.
Potential Benefits for Patients Living With PAH
The development of TRX-248 reflects an effort to address practical challenges associated with long-term PAH treatment.
Although existing treprostinil formulations play an important role in disease management, the administration methods may require patients to incorporate complex procedures and equipment into their daily lives.
Corsair believes a once-daily patch could offer an alternative that is easier to administer and potentially more convenient for patients who require ongoing treprostinil therapy.
The proposed system does not require an external pump, needle, or inhaler. Instead, patients would apply a transdermal patch designed to deliver the prodrug over a 24-hour period.
Multiple patch sizes are also intended to simplify dose titration, potentially allowing treatment adjustments through different patch configurations.
If successfully developed, the system could offer additional flexibility in treatment administration and help address some of the practical burdens associated with existing therapies.
Nevertheless, the potential advantages of TRX-248 will need to be evaluated in clinical studies involving patients with PAH. Important considerations will include drug exposure, skin tolerability, treatment adherence, dosing flexibility, and overall safety.
Company Leadership Highlights Development Progress
George Mahaffey, Chief Executive Officer of Corsair Pharma, emphasized the importance of developing alternative delivery approaches for established PAH treatments.
He noted that treprostinil is an established therapy for the disease, but the practical demands of existing administration methods can create challenges for patients and limit treatment flexibility.
Mahaffey stated that Corsair believes TRX-248 could help address these limitations by offering a convenient transdermal approach designed for once-daily administration.
He also highlighted the encouraging Phase 1 findings and the company’s intention to advance the program toward an IND submission while continuing engagement with the FDA.
Bobby Singh, M.Pharm., Ph.D., President and Chief Operating Officer of Corsair, described the FDA meeting outcome as an important development supporting the company’s bioequivalence-based 505(b)(2) strategy.
He confirmed that preparations are underway for the pilot bioequivalence study expected to begin in early 2027. The results will guide the final design of the pivotal study, which the company anticipates starting in late 2027.
Corsair Pharma’s positive pre-IND meeting outcome represents a significant step forward for its TRX-248 Transdermal System development program.
With FDA feedback supporting the proposed 505(b)(2) regulatory strategy, the company is preparing to advance the investigational treprostinil prodrug patch through a series of comparative pharmacokinetic studies.
The immediate priority is the planned pilot bioequivalence study in early 2027, followed by a pivotal study expected to begin in late 2027. Corsair anticipates receiving pivotal study data by the middle of 2028.
The program builds on encouraging Phase 1 findings demonstrating continuous treprostinil exposure during a 24-hour patch application and a favorable initial safety and tolerability profile.
By combining an established PAH therapy with proprietary prodrug technology and a once-daily transdermal delivery system, Corsair aims to develop a potentially more convenient treatment option for patients who require long-term treprostinil therapy.
If successful, TRX-248 could provide an alternative to existing infusion-based and inhaled administration approaches, potentially improving treatment flexibility and reducing certain administration-related challenges.
The company’s next development milestones will focus on generating the bioequivalence evidence necessary to support its regulatory strategy and advancing TRX-248 toward potential approval for pulmonary arterial hypertension.
About Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a rare, progressive, and fatal disease in which narrowed or blocked arteries in the lungs raise blood pressure and strain the heart. The disease affects approximately 45,000 people in the United States and can cause shortness of breath, fatigue, chest pain, edema, and heart failure.
About Prostacyclin Therapy and Treprostinil
One of the most effective therapies for PAH is treprostinil, a prostacyclin analog that dilates blood vessels and inhibits smooth muscle proliferation and platelet aggregation. United Therapeutics® and Liquidia® market treprostinil in subcutaneous, intravenous, oral, and inhaled formulations that improve symptoms and function.
However, infused therapies require pumps and carry central-line or infusion-site risks, inhaled therapies require multiple daily treatments and can cause cough, and oral therapy can cause dose-limiting side effects. Corsair estimates that these administration and tolerability burdens limit prostacyclin use to 30% to 35% of eligible patients. The U.S. prostacyclin market is approximately $4.3 billion annually. Corsair is evaluating its once-daily TRX-248 patch to confirm it can provide steady and continuous treprostinil exposure with less administration burden.
About Corsair Pharma, Inc.
Corsair Pharma is developing transformative solutions to improve the therapeutic profile of medications and provide superior treatment options for patients. Its lead program, the TRX-248 Transdermal System, is a once-daily treprostinil prodrug patch being evaluated for the treatment of pulmonary arterial hypertension. TRX-248 is a proprietary molecule covered by issued patents including composition of matter and other protections.
Corsair is advancing TRX-248 Transdermal System through a bioequivalence-based 505(b)(2) development pathway that leverages treprostinil’s established clinical profile. The company’s prodrug and transdermal technologies have potential applications for other pulmonary and systemic diseases. Corsair is backed by New Rhein Healthcare Investors, LLC, which led the recent financing rounds. The TRX-248 Transdermal System has not received marketing approval from the U.S. Food and Drug Administration, and the Company is awaiting FDA’s acceptance of its Investigational New Drug (IND) request to begin investigational clinical research. For more information, visit www.corsairpharma.com.