ALNY/RHHBY's Zilebesiran to Enter Phase III After Third Phase II Win

Alnylam Pharmaceuticals ALNY and partner, Roche RHHBY, reported positive results from a mid-stage study, evaluating the efficacy and safety of zilebesiran in patients with uncontrolled hypertension and high cardiovascular (CV) risk on two or more background antihypertensives.

Zilebesiran is an investigational subcutaneously administered RNAi therapeutic. The data readout is from Cohort A of the phase II KARDIA-3 study, which assessed the candidate in patients with eGFR ≥ 45 mL/min/1.73m2. The results were recently presented at a medical conference in Spain.

ALNY’s Phase II KARDIA-3 Study Cohort A Results in Detail

Per the data readout from Cohort A, the KARDIA-3 study achieved its primary endpoint of placebo-adjusted reductions in office systolic blood pressure (SBP) at month 3 with a single 300 mg dose of Alnylam/Roche’s zilebesiran. Despite being clinically meaningful, the study did not meet the pre-specified definition for statistical significance. Treatment with the candidate also led to a clinically meaningful reduction in 24-hour mean ambulatory SBP at three months. Both effects were maintained through six months compared to placebo. The higher 600 mg dose did not produce additional benefit at either time point.

Year to date, ALNY stock has soared 89.8% compared with the industry’s 2.7% growth.

The 300 mg dose also delivered greater SBP reductions at months 3 and 6 in a subgroup of patients on at least two antihypertensives, including a diuretic, and with baseline office SBP of 140 mmHg or higher. This supports the potential use of the candidate in combination with any standard antihypertensive therapies. Blood pressure improvements were sustained across the full six-month period and throughout the 24-hour cycle, with notable effects during nighttime hours, a key predictor of CV risk.

Alnylam/Roche’s zilebesiran further achieved early and durable reductions in CV and renal biomarkers, including NT-proBNP and UACR, among patients with elevated baseline levels, indicating potential for longer-term benefits in high-risk populations. The candidate demonstrated an encouraging safety profile with most adverse events being mild or moderate in severity.

Alnylam and Roche plan to report results from Cohort B of the KARDIA-3 study at an upcoming medical meeting. The companies have earlier reported encouraging results from the phase II KARDIA-1 and KARDIA-2 studies, demonstrating the effectiveness of zilebesiran in reducing blood pressure and its potential to be a best-in-class treatment providing transformational benefit in patients with hypertension at high CV risk.

ALNY’s Next Steps in the Development of Zilebesiran

Based on the encouraging data from the phase II KARDIA program, Alnylam and Roche are gearing up to initiate a global phase III cardiovascular outcomes trial (CVOT), ZENITH, to evaluate the potential of zilebesiran to reduce the risk of major adverse cardiovascular events.

Alnylam and Roche have filed applications with global regulators seeking permission to launch the phase III ZENITH study, which is expected to start by late 2025. The CVOT will enroll about 11,000 patients and evaluate zilebesiran (300 mg every six months) compared to placebo in individuals with uncontrolled hypertension and either established CV disease or elevated risk, all of whom are on at least two antihypertensives, including a diuretic. The primary endpoint of the ZENITH study is to evaluate whether zilebesiran lowers the risk of CV death, nonfatal myocardial infarction, nonfatal stroke, or heart failure events (hospitalization or urgent visits) compared with placebo.

Alnylam entered into a strategic collaboration with Roche to co-develop and co-commercialize zilebesiran for the treatment of hypertension in 2023.

Alnylam Pharmaceuticals, Inc. Price and Consensus

Alnylam Pharmaceuticals, Inc. price-consensus-chart | Alnylam Pharmaceuticals, Inc. Quote

ALNY’s Zacks Rank and Stocks to Consider

Alnylam currently carries a Zacks Rank #3 (Hold).

Some better-ranked stocks in the biotech sector are CorMedix CRMD and Kiniksa Pharmaceuticals KNSA, each sporting a Zacks Rank #1 (Strong Buy) at present. You can see the complete list of today’s Zacks #1 Rank stocks here.

In the past 60 days, estimates for CorMedix’s earnings per share have increased from $1.10 to $1.49 for 2025. During the same time, earnings per share estimates for 2026 have increased from $1.46 to $2.16. Year to date, shares of CRMD have surged 83.1%.

CorMedix’s earnings beat estimates in each of the trailing four quarters, delivering an average surprise of 34.85%.

In the past 60 days, estimates for Kiniksa Pharmaceuticals’ 2025 earnings per share have increased from 74 cents to $1.03. Earnings per share estimates for 2026 have increased from $1.19 to $1.60 during the same period. KNSA stock has surged 69.3% year to date.

Kiniksa Pharmaceuticals’ earnings beat estimates in two of the trailing four reported quarters and missed on the remaining two occasions, delivering an average negative surprise of 330.56%.

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