Corsair planning Phase 1 trial of treprostinil skin patch for PAH
Positive results seen in preclinical studies of skin patch delivery system
Corsair Pharma successfully completed preclinical studies testing its skin patch delivery system for treprostinil as a treatment for pulmonary arterial hypertension (PAH), and is now planning to launch a Phase 1 clinical trial in the next few months.
That’s according to new updates from the U.S.-based company, which already markets treprostinil in a number of other formulations for treating PAH. Corsair’s new approach, dubbed the TRX-248 Transdermal System, aims to provide a continuous and steady supply of the medication through a convenient and noninvasive skin patch.
Applied once a day, it delivers an inactive precursor, or prodrug, of treprostonil that’s absorbed into the bloodstream through the skin and is converted rapidly into active treprostonil in the liver.
“Across several studies in minipigs, the transdermal formulations of the proprietary prodrug were optimized to demonstrate steady and therapeutically meaningful blood levels of treprostinil with acceptable skin tolerability,” Bobby Singh, PhD, president and chief operating officer for Corsair, said in a company press release.
With the completion of these studies — including toxicological tests conducted according to laboratory principles that are essential to allow advancement into Phase 1 trials — “we look forward to the initiation of human studies in the coming months,” Singh said.
Corsair: Skin patch delivery system now ready for testing in humans
PAH is characterized by a narrowing of the pulmonary arteries, or the blood vessels that carry blood from the heart to the lungs. As a result of that narrowing, pressure in these vessels rises, making it harder for the heart to pump blood through the lungs and out to the rest of the body.
Individuals with PAH experience symptoms such as shortness of breath, fatigue, weakness, and compromised exercise capacity. Also, the heart is weakened over time, which can lead to heart failure.
Treprostinil is a lab-made version of prostacyclin, a naturally occurring hormone that helps blood vessels relax and widen, thereby boosting blood flow. It helps to improve exercise abilities, and to ease symptoms and delay disease progression, in people with PAH.
The first approved treprostinil formulations for PAH patients were subcutaneous, or under-the-skin, and intravenous, or into-the-vein, infusion versions from United Therapeutics. Sold under the brand name Remodulin, with generics available, these formulations have been marketed in the U.S. since the early 2000s. United has since also started marketing treprostinil as extended-release oral tablets (sold as Orenitram) and an inhaled solution (available as Tyvaso).
Each current delivery system for treprostinil has drawbacks for patients. … A once daily TRX-248 Transdermal System that conveniently provides steady and continuous doses in humans should be a significant improvement for the management of PAH.
There are pros and cons to each mode of administration, according to Corsair.
Infusion formulations have the benefit of allowing for a continuous supply of medication to optimize symptom control, while intravenous administration requires a catheter, or tube, to be inserted into a vein in the chest. Subcutaneous delivery requires a needle to be continuously implanted under the skin, which can cause painful reactions at the injection site.
While oral delivery is less invasive, it does not provide a steady supply of treprostinil, leading to fluctuations in the medication’s levels in the bloodstream. This leads to side effects when levels get high and poor symptom control when they’re low, Corsair notes on its website. Meanwhile, inhaled versions require multiple daily doses and can cause throat irritation.
Such administration issues led Corsair to team up with United in 2018 to develop the skin patch. It intends to offer the benefits of infusion formulations by providing a steady supply of medication, while avoiding the disadvantages of the more invasive approaches, and with fewer expected side effects.
“Each current delivery system for treprostinil has drawbacks for patients,” said George Mahaffey, Corsair’s CEO. “A once daily TRX-248 Transdermal System that conveniently provides steady and continuous doses in humans should be a significant improvement for the management of PAH.”
Corsair announced in 2023 it had secured $23 million in financing to support the therapy’s clinical development.
But before investigational treatments can be tested in humans, studies in animal models have to establish their pharmacological properties and make sure there are not any toxicity concerns. That’s what was successfully established in the minipig studies, enabling the company to move forward with plans for a Phase 1 trial, the company noted.
Accumulating evidence suggests that treprostinil or other medications in its class could be of benefit for forms of pulmonary hypertension beyond PAH. Corsair believes this may also be true for its transdermal treprostinil prodrug system.
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