Alnylam's ALN-6400 heads toward first human safety data in HHT this year
A Phase 1/2 trial testing Alnylam's plasminogen-targeting RNAi drug in hereditary hemorrhagic telangiectasia is set to post healthy-volunteer safety data after a 20-month completion-date slip.
Executive Summary
- Alnylam is heading toward its first human safety readout for a plasminogen-targeting RNAi drug in a rare bleeding disorder, following an earlier laboratory signal that supported moving into patients.
- The primary measure is adverse-event frequency in healthy volunteers and HHT patients, so the readout will tell investors whether the drug is tolerable before any efficacy signal can be assessed.
- The trial's primary completion date has moved out substantially since the study began, even as the sponsor has repeatedly reaffirmed the same second-half timing for the data readout across multiple disclosures.
- No competing drug shares this trial's target or mechanism in hereditary hemorrhagic telangiectasia, leaving this readout without a direct precedent to benchmark against in that indication.
The setup
Alnylam expects to report Phase 1 data for ALN-6400 in healthy volunteers in the second half of 2026, alongside a related Phase 2 readout in HHT patients on the same timeline. The trial, NCT06659640, is a two-part Phase 1/2 study: Part A dosing healthy adult volunteers, Part B dosing adult patients with a clinical diagnosis of HHT, a rare disorder that causes recurrent, difficult-to-control bleeding, most commonly nosebleeds. The primary endpoint in both parts is the frequency of adverse events, meaning the readout is designed to establish tolerability rather than efficacy. Secondary endpoints include change from baseline in plasminogen plasma activity and protein levels in both parts, and, in Part B, epistaxis frequency, duration and intensity, hemoglobin, iron infusion use, and quality-of-life scores. Alnylam+1Alnylam Launches “Alnylam 2030” Strategy to Drive Next Era of Growth and Patient ImpactJan 11, 2026A Study to Evaluate ALN-6400 in Healthy Volunteers and Patients With Hereditary Hemorrhagic Telangiectasia (HHT)NCT06659640
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
Prior signal
In February 2025, Alnylam presented first-cohort Phase 1 data for ALN-6400 at its research and development day, describing a favorable impact on an ex-vivo hemostasis assay, a laboratory test of blood-clotting function run outside the body. That result came before this trial's current primary completion date and represents the clinical program's first disclosed signal ahead of the pending H2-2026 readout.
Timing history
The trial's primary completion date has moved three times since the study was first posted: from May 2026 to September 2025 in December 2024, then out to August 2026 in September 2025, then to January 2028 in October 2025, a cumulative delay of 847 days from the earliest registered date. Enrollment rose in the same window, from an anticipated 32 to 96 in September 2025 and then to 120 later that month, alongside a brief move to Active, not recruiting before the trial re-entered Recruiting status. Enrollment has held at 120 since, a 0% change against that revised target, which the trial's own operational thresholds treat as a routine, unflagged level. Despite the completion-date slippage, Alnylam has repeated the same H2-2026 guidance window for this data readout across disclosures in January, February and April 2026. NCT06659640+1A Study to Evaluate ALN-6400 in Healthy Volunteers and Patients With Hereditary Hemorrhagic Telangiectasia (HHT)NCT06659640Alnylam Launches “Alnylam 2030” Strategy to Drive Next Era of Growth and Patient ImpactJan 11, 2026
Competitive frame
No trial sharing ALN-6400's mechanism or target is running in HHT, and a broader scan of trials in healthy-volunteer study designs found no drug testing the same molecular pathway. That places this readout without a direct mechanistic precedent in its indication: the nearest comparators identified across healthy-volunteer Phase 1 studies, such as Biogen's BIIB115 and PYC Therapeutics' PYC-003, target unrelated genes and diseases and serve only as contextual, not mechanistic, neighbors. Given that structural isolation, the readout that would be informative is one showing an adverse-event rate consistent with the trial's own safety margins in both healthy volunteers and HHT patients, paired with a plasminogen activity change that tracks the direction seen in the 2025 ex-vivo assay.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.