Cereno Scientific has announced positive topline results from its Phase IIa trial of CS1 in patients with pulmonary arterial hypertension (PAH). The trial, CS1-003, met its primary endpoint, demonstrating that CS1 is safe and well-tolerated. Furthermore, the study indicated a positive impact on clinically relevant parameters, suggesting the drug's potential as a disease-modifying therapy.
The Phase IIa trial, conducted across 10 clinical sites in the US, randomized 25 patients to CS1 treatment, with 21 completing the trial without significant protocol deviations. The study evaluated the safety, tolerability, pharmacokinetics, and exploratory efficacy of CS1 on top of standard-of-care treatments for PAH.
Safety and Tolerability
The primary endpoint of the trial focused on safety and tolerability. Results indicated:
- No CS1-related serious adverse events, including hospitalizations or mortality.
- No clinically significant changes in liver lab values or drug-related platelet decreases or bleedings.
- Overall, CS1 was well-tolerated by the patients.
Exploratory Efficacy Parameters
Beyond safety, the trial explored several clinical efficacy parameters. Data from the three doses were pooled due to therapeutic drug exposure across all dose groups. The results showed:
- REVEAL Risk Score: 43% of patients (9/21) improved their risk score, and 71% (15/21) either improved or maintained a stable risk score.
- Functional Class: 33% of patients (7/21) improved their functional class, and 86% (18/21) improved or maintained a stable functional class.
- Mean Pulmonary Arterial Pressure (mPAP): 67% of patients (14/21) experienced a sustained reduction in pulmonary arterial pressure.
Dr. Raymond Benza, Network Director of Pulmonary Hypertension at Mount Sinai Icahn School of Medicine, commented on the results: "PAH is a rare and devastating disease... Despite advances in treatment options, there is still a pronounced need for effective, safe, and disease-modifying therapies for these patients. The results presented today... are promising."
Reversing Pathological Remodeling
Further analysis of a subgroup of patients revealed that 25% (5/21) showed significant reductions in pulmonary vascular resistance (PVR), with reductions greater than 30% (range 35-51%, mean 45%). These reductions in PVR were associated with increases in right ventricular stroke volume, suggesting a potential reversal of vascular remodeling.
Cereno Scientific's CEO, Sten R. Sørensen, stated, "These results, together with our foundation of preclinical data, strengthen our conviction that CS1 is a disease-modifying therapy for PAH. We are excited to now move forward with the next development phase with CS1."
Next Steps for CS1
Cereno Scientific plans to engage with regulatory authorities to discuss the design of a pivotal trial for CS1 in PAH. The company will also continue enrolling patients in its Expanded Access Program, which allows patients who completed the Phase IIa trial to continue receiving CS1 treatment.
Dr. Rahul Agrawal, CMO and Head of R&D at Cereno Scientific, added, "The CS1-003 trial demonstrated compelling signs of clinical efficacy already over a 12-week treatment period, and we expect to see additional positive impact of CS1 with longer use of our drug in patients with PAH."
About Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension is a progressive disease characterized by the narrowing of pulmonary arterial vessels, leading to right heart failure and reduced life expectancy. Current treatments primarily focus on managing symptoms, with a significant unmet need for therapies that address the underlying causes of the disease.
