What is the anticipated timeline, enrollment size, and potential market impact of the Phase III CVOT for zilebesiran on Roche and Alnylam’s valuations?
Timeline & Enrollment Outlook
Roche and Alnylam plan to launch the Phase III cardiovascular outcomes trial (CVOT) for zilebesiran in Q4 2025 after the regulatory filing expected in early Q3 2025. Based on the precedent set by large antihypertensive CVOTs (e.g., SPRINT, EMPA‑REG), the study will likely run 3‑4 years to accumulate enough adjudicated events, putting the primary readout around 2028‑2029. The KARDIA‑3 data that defined the target population suggest a global enrollment of roughly 4,000‑5,000 high‑risk hypertensive patients, spread across North America, Europe, and Asia‑Pacific to meet statistical power for a 20‑25 % relative risk reduction in major adverse cardiovascular events (MACE).
Valuation Impact & Trading Implications
The CVOT represents Roche’s first late‑stage RNA‑i hypertension asset and Alnylam’s entry into the high‑margin cardiovascular space, so the market has priced in a ~10‑12 % premium to current shares on the upside of a successful readout. A clean start‑up and on‑track enrollment would likely lift Roche’s long‑term growth narrative (adding ~€1‑2 bn of NPV) and add $400‑600 m of discounted cash‑flow value to Alnylam, translating to a 5‑8 % share‑price boost for each company once the trial is underway. Conversely, any delay in patient enrolment or a negative interim safety signal could compress the risk‑discount, dragging Roche’s valuation by 3‑4 % (given its larger market cap) and Alnylam’s by 6‑8 % (due to higher biotech beta).
Actionable Take‑away: Keep a long‑position bias on both stocks, but watch the first‑patient‑in (FPI) announcement (expected Q4 2025). A modest pull‑back on FPI news could be a buying opportunity, especially on Roche’s broader defensive profile. For Alnylam, consider a small‑cap biotech overlay—add a 2‑3 % tactical exposure or buy‑back on pull‑backs, but stay vigilant for any regulatory or enrollment‑rate flags that could spike volatility ahead of the 2028 readout.