Janssen Pharmaceutical has updated the Phase 3 MACiTEPH study, which evaluates macitentan 75mg in patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH). The company has decided to halt the MACiTEPH trial due to futility, based on a recommendation from the independent data monitoring committee following a pre-planned interim analysis. Notably, no new safety concerns have arisen from these interim findings.
It's worth noting that the outcomes of the interim analysis in the MACiTEPH study have no impact on any of Janssen's currently available pulmonary hypertension treatments. Moreover, the pivotal Phase 3 UNISUS study, which aims to establish the superiority of a 75 mg dose of macitentan over the existing 10 mg dose for patients with pulmonary arterial hypertension, is continuing as scheduled.
Janssen takes pride in its long-standing commitment to advancing scientific research to benefit individuals dealing with pulmonary hypertension.
Roche and Alnylam have released positive topline findings from the Phase 2 study KARDIA-1, which assesses the potential of zilebesiran, an experimental RNAi therapeutic, in treating hypertension among patients with a heightened risk of cardiovascular disease. In the study, zilebesiran successfully achieved its primary objective, showcasing a remarkable reduction in systolic blood pressure (SBP) of more than 15 mmHg after three months of treatment compared to a placebo.
Furthermore, the study demonstrated consistent and sustained reductions in SBP after six months of treatment, supporting the feasibility of quarterly or biannual dosing. Zilebesiran displayed a promising safety and tolerability profile, particularly in adult patients with mild-to-moderate hypertension. A comprehensive presentation of the study's results is slated for an upcoming scientific conference.
Roche and Alnylam jointly announced that KARDIA-1's Phase 2 trial of zilebesiran, which targets liver-expressed angiotensinogen (AGT), achieved its primary objective. This experimental RNAi therapy led to a clinically significant reduction in 24-hour mean SBP within three months, with a placebo-subtracted reduction exceeding 15 mmHg for both the 300 mg and 600 mg dosages. The study also met critical secondary endpoints by demonstrating consistent and sustained SBP reductions over six months, reinforcing the potential for periodic dosing. Additionally, the research indicated that zilebesiran effectively reduced serum AGT levels over six months while maintaining a favorable safety and tolerability profile.
The Phase 2 trial KARDIA-1 was designed as a randomized, double-masked, placebo-controlled, multicenter global dose-ranging study. The primary objective of the study was to assess the effectiveness and safety of zilebesiran when used as the sole treatment for mild-to-moderate hypertension in adult patients. The study enrolled a diverse group of 394 adults, including those with untreated hypertension and those on stable treatment with one or more anti-hypertensive medications after a washout period.
Hypertension represents a growing global health crisis, contributing to approximately 10 million deaths annually worldwide. Roughly one in three adults worldwide suffers from hypertension. Despite the availability of various oral anti-hypertensive treatments, up to 80% of individuals fail to achieve controlled blood pressure, leaving them at a higher risk of cardiovascular, cerebrovascular, and renal diseases.
Earlier this year, Roche joined forces with Alnylam to co-develop and co-commercialize zilebesiran. The KARDIA study program also encompasses the Phase 2 study KARDIA-2, which explores using zilebesiran in combination with one of three standard classes of anti-hypertensive medications. This study completed enrollment in June 2023, with topline results expected in early 2024.
Zilebesiran is an investigational RNAi therapeutic administered subcutaneously, targeting angiotensinogen (AGT) and developed to address hypertension in populations with high unmet medical needs. AGT is the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS). It is a cascade with established significance in blood pressure (BP) regulation, featuring well-documented anti-hypertensive effects upon its inhibition. Zilebesiran inhibits AGT synthesis in the liver, potentially leading to durable reductions in AGT protein and, ultimately, in the vasoconstrictor angiotensin (Ang) II. This approach can maintain consistency and lasting blood pressure reduction throughout the 24 hours, sustained for up to six months after a single dose of zilebesiran.