CS1 shows favorable safety in PAH in one-year access program
Expanded access data support tolerability of experimental therapy
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Treatment with CS1, a once-daily oral therapy being developed by Cereno Scientific, was found to be safe and well tolerated for people with pulmonary arterial hypertension (PAH), according to one-year data from an expanded access program (EAP).
The EAP (NCT06321705), also known as compassionate use in the U.S., allowed 10 patients who had completed a previous three-month Phase 2a clinical trial (NCT05224531) to continue receiving CS1 under physician supervision. The program was approved by the U.S. Food and Drug Administration in 2024, enabling the company to collect longer-term safety and efficacy data while allowing patients to maintain access to the therapy.
Longer-term data support CS1 safety beyond initial trial
Together, the Phase 2a trial and the EAP provide up to 15 months of treatment experience with CS1. According to the company, initial long-term safety findings from the EAP were consistent with those observed in the earlier Phase 2a study.
Preparations for a global Phase 2b trial testing CS1 in a larger group of about 126 people with PAH are ongoing, with the first patient expected to be enrolled in June.
“The accumulated clinical Phase II data representing up to 15 months of treatment with CS1 in patients with PAH, provides us with further confidence in our goal to develop and deliver CS1 as a new treatment for patients with PAH,” Sten R. Sörensen, Cereno’s CEO, said in a company press release.
According to Sörensen, “the results from the EAP study support the value proposition of CS1 as an oral, once-daily PAH therapy with a favorable safety and tolerability profile and potential disease-modifying effects.”
A type of pulmonary hypertension, PAH is marked by pulmonary vascular remodeling, a process involving structural changes in the walls of lung blood vessels caused by abnormal cell growth. This narrows the vessels that carry blood from the heart to the lungs (pulmonary arteries), restricting blood flow, increasing blood pressure, and ultimately leading to hallmark PAH symptoms including shortness of breath, heart palpitations, excessive fatigue, and dizziness.
CS1 is a reformulation of the anti-seizure medicine valproic acid, which has been reported to have pressure-relieving, anti-inflammatory, and anti-scarring properties. According to the company, the therapy is designed to target key disease-driving mechanisms such as pulmonary vascular remodeling, fibrosis, and inflammation, with the potential to act as a disease-modifying treatment.
Phase 2a trial evaluated safety and early signals of benefit
The Phase 2a trial was designed to explore the safety, tolerability, and preliminary efficacy of CS1 when added to standard care in 25 adults, ages 18 to 80, with PAH. Participants were randomly assigned to receive one of three daily oral doses — 480 mg, 960 mg, or 1,920 mg — for 12 weeks, or about three months.
Top-line data showed that the therapy was safe and well tolerated, with no drug-related serious adverse events, meeting the study’s main goal. Treatment also stabilized or improved REVEAL risk scores — a validated measure of mortality risk in PAH — in most participants (71%).
Data from implanted CardioMEMS devices, which allow daily, noninvasive monitoring of arterial blood pressure, suggested that about two-thirds of patients (67%) had sustained reductions in pulmonary artery pressure.
The EAP was initiated following positive results from the Phase 2a trial. Cereno now reports that early safety findings demonstrate that CS1 was well tolerated and not associated with any unexpected safety concerns or deaths. There were also no discontinuations reported to be related to CS1.
Most patients completed one year of treatment in access program
Overall, six of 10 patients completed the full year of continuous treatment in the EAP. Among the remaining four participants, two discontinued treatment after experiencing episodes of atrial fibrillation — a type of irregular heart rhythm — that were deemed unrelated to CS1, one withdrew study consent, and one was lost to follow-up.
“These results provide important confirmation that the favorable safety and tolerability profile observed in the Phase IIa trial is maintained over longer-term use,” said Rahul Agrawal, MD, chief medical officer and head of research and development at Cereno.
“In PAH, where existing therapies can be associated with safety and tolerability challenges, there remains a significant unmet need for safer, well-tolerated treatment options,” Agrawal added. “These findings support the continued development of CS1 as a potential disease-modifying therapy.”
Cereno expects to report further data from the EAP in the second quarter of 2026. These will include exploratory analyses of the long-term effects of CS1 on pulmonary arteries in a subset of patients, using a noninvasive imaging technology called Functional Respiratory Imaging (FRI) developed by Fluidda.
