Roche and Alnylam to Launch Phase 3 Study for Hypertension Drug

Roche and Alnylam will start a Phase 3 study for a new hypertension drug. The study aims to evaluate the drug's effectiveness in reducing cardiovascular outcomes in patients with hypertension. Roche is a research-based healthcare company with operating businesses in Pharmaceuticals and Diagnostics. Alnylam is a biotech company developing RNAi therapeutics. The study will be a significant step forward in the development of a new treatment option for hypertension.

Roche (SIX: RO, ROG; OTCQX: RHHBY) and Alnylam (Nasdaq: ALNY) have announced the initiation of a Phase III cardiovascular outcomes trial (CVOT) to evaluate the effectiveness of zilebesiran, a novel RNAi therapeutic, in reducing the risk of major adverse cardiovascular events in patients with uncontrolled hypertension. The study, named ZENITH (ZilebEsiraN CardIovascular OuTcome Study in Hypertension), is expected to enroll approximately 11,000 patients across over 30 countries [1].

Zilebesiran is an investigational drug that targets angiotensinogen (AGT), the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), which plays a key role in blood pressure regulation. It inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein and ultimately in the vasoconstrictor angiotensin (Ang) II. Zilebesiran utilizes Alnylam's Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, enabling infrequent biannual subcutaneous dosing and increased selectivity [1].

The decision to initiate the Phase III study was informed by the comprehensive KARDIA Phase II program, including KARDIA-1, KARDIA-2, and the most recent KARDIA-3 study. KARDIA-3, presented as a late breaker at the European Society of Cardiology Congress 2025, demonstrated clinically meaningful reductions in office systolic blood pressure (SBP) at month three with continuous control through month six. The study showed that a single dose of zilebesiran (300 mg every six months, subcutaneous injection) resulted in placebo-adjusted reductions of office SBP in all comers at the month three primary endpoint (-5.0 mmHg; p=0.0431) with sustained benefits out to month six (-3.9 mmHg; 95% CI: [-8.5, 0.7]). There were no additional benefits of the 600 mg dose at month three (-3.3 mmHg; p=0.1830) or month six (-3.6 mmHg; 95% CI: [-8.2, 1.0]). The study met the aim of identifying the patient population that could potentially benefit the most from zilebesiran and showed encouraging safety [1].

The ZENITH CVOT will evaluate zilebesiran (300 mg) every six months compared to placebo in patients with uncontrolled hypertension with either established CV disease or at high risk for CV disease on two or more antihypertensives, one being a diuretic. The primary objective will be to assess the impact of zilebesiran on reducing the risk of CV death, nonfatal myocardial infarction (MI), nonfatal stroke, or heart failure (HF) events (hospitalisation for HF or urgent HF visit), compared to placebo [1].

Hypertension is the primary cause of and number one modifiable risk factor for cardiovascular disease. An estimated one in three adults, over 1.2 billion people worldwide, have hypertension, and despite the wide availability of antihypertensives, up to 80% of them do not achieve adequate blood pressure control. Poor adherence to daily oral therapies is an important contributor to poor blood pressure control and CV outcomes. An effective long-acting therapy that provides continuous control of blood pressure may help to reduce the burden of uncontrolled hypertension [1].

This Phase III study represents a significant step forward in the development of a new treatment option for hypertension, potentially offering patients with uncontrolled hypertension a more effective and convenient alternative to current oral therapies. The results of this trial will be closely watched by investors and healthcare professionals alike, as they could have a substantial impact on the management of hypertension and the prevention of cardiovascular disease.

References:
[1] https://www.roche.com/media/releases/med-cor-2025-08-30