There is a major shift away from vasodilator therapy in pulmonary arterial hypertension (PAH), with more disease-modifying therapies entering the space.
In an exclusive interview with Pharmaceutical Technology, Cereno Scientific’s CEO Sten Sörensen said that previously the only drugs available for PAH were vasodilators, but recently, companies are attempting to develop disease-modifying therapies for the condition.
“PAH is going to move more towards hormonal control, epigenetic modulation and disease modification, and we think we're one of the pioneers with that,” said the CEO. Cereno Scientific is developing a PAH therapy, CS1, with a Phase II (NCT05224531) readout expected by the end of this month.
According to GlobalData, there are 13 therapies in Phase III development for PAH. Sorensen highlights MSD’s Winrevair (sotatercept) as a major disruptor in the space, following its FDA approval in 2023. Winrevair is an activin signalling inhibitor that has been clinically proven to increase exercise capacity and reduce the risk of clinical worsening events in patients with PAH in combination with standard-of-care therapy. Companies such as Johnson and Johnson and Eli Lilly are also approaching approval decisions for their PAH drugs.
GlobalData is the parent company of Pharmaceutical Technology.
Cereno’s CS1 is an HDAC inhibitor that treats PAH by increasing tissue plasminogen activator (tPA) gene expression. tPA is essential in the process of dissolving blood clots in blood vessels. The CEO also highlighted the therapy’s anti-thrombotic properties, saying that the company may consider investigating the drug for its use for other indications in the future.
“Therapies that solve thrombosis are useful in diseases that tackle inflammation, fibrosis, and hypertrophy,” said Sörensen.
The European Medicines Agency (EMA) granted Cereno an orphan drug designation for CS1 in PAH on 3 September. The US Food and Drug Administration (FDA) approved a compassionate use programme for the therapy on 31 January. In the current Phase II study, there have not been any significant safety signals thus far and Cereno predicts signs of disease modification will be observed in the final readout, said Sörensen.
PAH is a rare disease that affects arteries in the lungs, causing them to thicken and narrow. The American Lung Association reports that 500–1,000 new cases of PAH are diagnosed every year in the US.
Common treatments for PAH include different formulations of epoprostenol, GSK’s Flolan and Johnson and Johnson’s Veletri, and different versions of treprostinil, United Therapeutics’ Remodulin and Tyvaso, amongst other therapies. Both therapy types cause side effects such as headache, jaw discomfort, flushing, rashes, and stomach upset, as per Stanford Medicine. Furthermore, Flolan and Tyvaso can be more cumbersome for patients due to their intravenous catheter administration, causing a higher risk of infection.
Cereno is running the Phase II study in collaboration with Abbott. The two companies signed the partnership agreement in 2021, with Abbott’s CardioMEMS HF system, an implantable device for heart failure, being used in the trial to remotely monitor patients. Abbott is seeking approval for its CardioMEMs system for PAH.
