ALNY/RHHBY's Zilebesiran Advances to Phase III Following Third Phase II Success

Alnylam Pharmaceuticals and Roche Study Results

• Positive Mid-Stage Study Findings: Alnylam Pharmaceuticals and Roche reported promising results from a mid-stage study of zilebesiran, an RNAi therapeutic for patients with uncontrolled hypertension and high cardiovascular risk. The study, part of the phase II KARDIA-3 trial, showed that a single 300 mg dose achieved its primary endpoint of reducing office systolic blood pressure (SBP) at three months, although it did not meet the statistical significance threshold.

• Sustained Blood Pressure Reductions: The 300 mg dose led to clinically meaningful reductions in both office and 24-hour mean ambulatory SBP, effects that were maintained for six months. Notably, the higher 600 mg dose did not provide additional benefits.

• Subgroup Efficacy: In a subgroup of patients on at least two antihypertensives, including a diuretic, the 300 mg dose resulted in greater SBP reductions, indicating its potential for use alongside standard antihypertensive therapies.

• Biomarker Improvements: Zilebesiran also demonstrated early and durable reductions in cardiovascular and renal biomarkers, suggesting potential long-term benefits for high-risk populations. The treatment exhibited a favorable safety profile, with most adverse events being mild or moderate.

Future Plans and Trials

• Upcoming Cohort B Results: Alnylam and Roche plan to present results from Cohort B of the KARDIA-3 study at an upcoming medical meeting, building on previous encouraging findings from the KARDIA-1 and KARDIA-2 studies.

• Phase III ZENITH Trial: The companies are preparing to initiate a global phase III cardiovascular outcomes trial (CVOT), named ZENITH, aimed at evaluating zilebesiran's ability to reduce major adverse cardiovascular events. This trial will enroll approximately 11,000 patients and is expected to start by late 2025.

• Regulatory Applications: Alnylam and Roche have filed applications with global regulators to commence the phase III ZENITH study, which will compare zilebesiran (300 mg every six months) to placebo in patients with uncontrolled hypertension.

Stock Performance and Market Position

• Alnylam Stock Surge: Year-to-date, Alnylam's stock has increased by 89.8%, significantly outperforming the industry average growth of 2.7%.

• Comparative Stock Analysis: Other biotech stocks like CorMedix and Kiniksa Pharmaceuticals have also shown strong performance, with CorMedix's stock rising 83.1% and Kiniksa's by 69.3% year-to-date. Both companies have received positive earnings estimate revisions, indicating strong market positions.

• Zacks Rank: Alnylam currently holds a Zacks Rank of #3 (Hold), while CorMedix and Kiniksa Pharmaceuticals are rated #1 (Strong Buy), reflecting their favorable market outlooks.