CS1 is found safe, shows signs of efficacy in PAH: Top-line data
Cereno: Results strengthen 'conviction' that treatment is disease modifying
Cereno Scientific‘s investigational therapy CS1 was well tolerated and showed signs of clinical benefit in people with pulmonary arterial hypertension (PAH), according to top-line data from a Phase 2a clinical trial.
The company plans to start discussions with regulatory authorities and will pursue a pivotal clinical trial to help support the therapy’s approval in PAH.
“These results, together with our foundation of preclinical data, strengthen our conviction that CS1 is a disease-modifying therapy for PAH,” Sten R. Sörensen, Cereno’s CEO, said in a company press release. “We are excited to now move forward with the next development phase with CS1. Our mission is to … provide a valuable addition to the PAH toolbox of therapeutics.”
In PAH, a narrowing of the pulmonary arteries that carry blood from the heart to the lungs restricts blood flow and increases blood pressure. This drives declines in lung function and can cause right heart failure. Pulmonary artery narrowing in PAH is driven by a process called pulmonary vascular remodeling, where the cells that line blood vessel walls grow uncontrollably.
CS1 is a reformulation of the anti-seizure medicine valproic acid, which blocks the activity of histone deacetylase (HDAC), a group of enzymes that cause gene activity to be suppressed. It’s reported to have pressure-relieving, anti-inflammatory, and anti-scarring properties. Cereno expects the treatment to reverse the pulmonary vascular remodeling that drives the symptoms of PAH.
Outcomes of PAH with CS1
The Phase 2 CS1-003 trial (NCT05224531) was designed to explore the safety, tolerability, and preliminary efficacy of CS1 on top of standard of care in 25 adults with PAH who 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. The treatment was safe and well tolerated, meeting the study’s main goal, according to an update from Cereno.
Moreover, among the 21 patients who completed treatment per the trial’s protocol, most (71%) saw a stabilized or improved REVEAL risk score, a validated metric that considers several clinical factors to estimate the risk of death in PAH, with 43% showing improvement. Likewise, 86% had an improved or stable World Health Organization Functional Class, which describes how severely pulmonary hypertension symptoms affect daily physical functioning, with a third improving.
The participants were also implanted with a device called CardioMEMS that enables daily, noninvasive monitoring of pressure in the pulmonary arteries. Data from these devices showed two-thirds of patients (67%) had a sustained reduction in pulmonary artery pressure.
Overall, 25% of patients were deemed “remarkable responders,” who exhibited large reductions, by more than 30%, in pulmonary vascular resistance — a measure of how hard it is for blood to flow through vessels — and associated increases in the amount of blood the heart’s right ventricle was able to pump. Most of these patients were treated with the low dose of CS1, supporting the use of lower doses for study.
“I am very pleased with the positive outcomes we are seeing in our patients following treatment with CS1,” said Jason Guichard, MD, PhD, of the University of South Carolina School of Medicine Greenville and a trial investigator. “Their improvements in health and well-being are encouraging and reflect the potential effectiveness of the therapy.”
A therapy with ‘disease-modifying effects’
Taken together with recent preclinical data demonstrating that another of the company’s HDAC inhibitors had a positive impact on reverse vascular remodeling in small lung arteries, Cereno believes the findings suggest CS1 will have disease-modifying effects in PAH.
Eligible patients who complete the Phase 2a trial may continue to receive CS1 as part of an expanded access program that was approved by U.S. regulators this year. Most of his patients have expressed interest in enrolling, Guichard said.
The program will allow the company to collect more long-term data on CS1’s safety and efficacy. Rahul Agrawal, MD, chief medical officer and head of research & design at Cereno, said that given the “compelling signs of clinical efficacy” seen after three months, Cereno expects “additional positive impact of CS1 with longer use.”
Cereno also recently signed an agreement with the medical technology company Fluidda to conduct a trial that will use noninvasive imaging technology to visualize CS1’s ability to reverse pulmonary vascular remodeling in a PAH clinical setting. Some patients enrolled in the expanded access program plan to participate.
“This work will give us a deeper understanding of our lead candidate CS1 and further support us in optimizing the road to approval of CS1, and subsequently into the clinic, for the benefit of patients suffering from PAH,” Agrawal said in a separate press release.
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