Cereno aligns with FDA on CS1 development path for PAH
Developer reports 'productive' meeting with regulators on future trial
Cereno Scientific has completed a type C meeting with the U.S. Food and Drug Administration (FDA) about the design of a future Phase 2b clinical trial to test CS1, its lead therapy candidate for people with pulmonary arterial hypertension (PAH).
Besides defining the trial’s design, the meeting, held last week, addressed further steps in CS1’s clinical development.
The therapy has already been tested in a Phase 2a clinical trial that assessed its safety and “exploratory efficacy.” That study found CS1 to be well tolerated and to show benefits in adults with PAH.
“We had a productive discussion with the FDA regarding the further clinical development of our promising [candidate] CS1,” Rahul Agrawal, MD, Cereno’s chief medical officer and head of research and development, said in a company press release, noting he was “very pleased with the discussions.”
The company plans to provide further updates once it receives the official minutes from the meeting with FDA, which are expected in about a month.
“The team at the FDA [has] extensive experience in clinical trials and what is needed for marketing authorizations, so it is very important to utilize the meeting time optimally ensuring that our questions are answered,” Agrawal said.
CS1 found safe, well tolerated in earlier clinical trial
PAH is characterized by the narrowing of the pulmonary arteries, the blood vessels that carry blood from the heart to the lungs. Such narrowing occurs due to vascular remodeling, or the excessive growth of cells that line blood vessels. This restricts blood flow and increases blood pressure, making it harder for the heart’s right lower chamber to pump blood through the lungs. The condition can ultimately lead to heart failure.
CS1 is Cereno’s proprietary reformulation of the antiseizure treatment valproic acid. It serves as an epigenetic modulator, meaning it regulates gene activity without altering the DNA sequence.
Specifically, the therapy blocks the activity of a group of enzymes, called histone deacetylases or HDAC, that suppress gene activity. Preclinical data suggested that HDAC suppression has anti-inflammatory, anti-scarring, pulmonary pressure-reducing, and anti-blood clotting effects. Those findings supported CS1 as a potential treatment for PAH.
The FDA has awarded the therapy orphan drug designation from the FDA, which is granted to treatments for rare diseases. The status is meant to provide financial incentives for drug development and FDA support in clinical trial design. It also allows seven years of market exclusivity should a therapy be approved.
It is a sound strategy to seek advice from the authorities several times during the clinical development of a drug candidate to ensure that expectations are aligned from both parties.
The earlier Phase 2a trial (NCT05224531), called CS1-003, enrolled 25 adults with PAH who were randomly assigned to receive one of three daily doses of CS1 for about three months.
The treatment was shown to be safe and well tolerated, and to stabilize or reduce REVEAL risk scores in 71% of the 21 patients completing the trial. REVEAL is a validated measure to estimate the risk of death in PAH.
In the trial, 86% of patients also experienced an improvement or stabilization in the New York Heart Association (NYHA) functional class, a system for classifying the severity of heart failure based on symptoms. A total of 67% of participants had sustained reductions in mean pulmonary arterial blood pressure.
Further data showed that CS1 treatment was associated with improved right heart function, while symptoms associated with heart failure and the risk of clinical worsening and mortality were reduced over time. Quality of life was also improved, per the study data.
Patients who completed the trial were able to enroll in expanded access program sponsored by the company, in which participants continue to receive the experimental therapy. This expanded program is expected to generate long-term safety and efficacy data.
The planned Phase 2b trial will be a larger placebo-controlled study meant to confirm the clinical effects of CS1.
Sten R. Sörensen, Cereno’s CEO, called the company’s interactions to date with the FDA “insightful.”
“It is a sound strategy to seek advice from the authorities several times during the clinical development of a drug candidate to ensure that expectations are aligned from both parties,” Sörensen said.
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