CS1 improves right heart function in PAH: New trial data
Symptoms tied to heart failure and risk of clinical worsening, mortality declined
Cereno Scientific‘s investigational oral therapy CS1 improves right heart function in people with pulmonary arterial hypertension (PAH), according to new data from a Phase 2a clinical trial.
Three months of treatment also boosted quality of life, while symptoms associated with heart failure and the risk of clinical worsening and mortality lessened over time.
The company plans a larger placebo-controlled Phase 2b study to confirm and expand upon these findings. Cereno has recently requested a Type C meeting with the U.S. Food and Drug Administration (FDA) to ensure its strategy aligns with the agency’s requirements.
“Despite the trial’s short duration, CS1 showed improvement of right ventricular function, signaling a disease-modifying effect by halting disease progression,” Rahul Agrawal, chief medical officer and head of R&D at Cereno, said in a company press release. “We have now initiated a Type C meeting with the FDA to align the next development steps of CS1.”
In PAH, pulmonary vascular remodeling, or the uncontrollable growth of cells that line blood vessels, drives a narrowing of the pulmonary arteries that carry blood from the heart to the lungs. This restricts blood flow and increases blood pressure, making it harder for the heart’s right ventricle to pump blood through the lungs. Over time, this can lead to heart failure.
CS1 is a proprietary reformulation of the anti-seizure medicine valproic acid that acts as an epigenetic modulator. That is, it blocks the activity of histone deacetylases (HDAC), a group of enzymes that suppress gene activity. Cereno expects CS1 to modify disease-related epigenetic processes, reverse the pulmonary vascular remodeling that drives symptoms, and extend patient survival.
Gains with CS1
The Phase 2a trial (NCT05224531) tested CS1’s preliminary efficacy alongside standard of care in 25 adults with PAH. The participants were randomly assigned to receive one of three daily doses (480 mg, 960 mg, or 1,920 mg) for 12 weeks, or about three months.
Top-line data from the 21 patients who completed the trial’s protocol showed that CS1 was safe and well tolerated, and stabilized or improved REVEAL risk scores, a validated measure that accounts for several clinical factors that estimate the risk of death in PAH.
Likewise, improvements were observed in the New York Heart Association functional class, a system for classifying the severity of heart failure based on symptoms. Moreover, two-thirds of patients (67%) had sustained reductions in mean pulmonary arterial blood pressure.
In the newly reported data, CS1 significantly lessened right-ventricular Global Longitudinal Strain, a predictor of right-heart remodeling during the early stages of the disease and future mortality, according to Cereno.
Three months of treatment stabilized or improved tricuspid regurgitation, where the heart valve between the two right chambers fails to close entirely during right ventricular contraction, leading to increased blood pressure.
REVEAL risk scores and NYHA functional class continued to improve over time, which positively impacted the quality of life of PAH patients, as measured by PAH-SYMPACT and the Minnesota Living with Heart Failure Questionnaire.
The investigators also identified a subgroup of participants in the early stage of PAH who saw marked improvement in pulmonary vascular resistance, a measure of the internal resistance to blood flow within the lung’s blood vessels.
“All signs are pointing toward our epigenetic modulating HDACi CS1 having a real potential to be a disease-modifying game changer in the treatment of PAH,” said Sten R. Sörensen, Cereno’s CEO.“
The company recently announced it had enrolled 10 patients who completed the Phase 2a trial in its expanded access program (EAP), which the FDA approved in 2024. Continued treatment with CS1 in the EAP is expected to generate additional long-term safety and efficacy data.
To advance the EAP and win FDA approval to continue evaluating CS1 in a Phase 2b or pivotal Phase 3 trial, Cereno recently secured loan financing of at least 250 million Swedish crowns (almost $23.6 million).
“We are excited for the next part of the journey to further evaluate CS1’s transformative potential as a treatment for PAH,” Sörensen said.
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