ALN-6400

In HHT, some arteries connect straight into veins without the tiny capillaries that normally sit between them. These connections are called arteriovenous malformations, and the small ones near the surface of the skin, visible as red marks, are called telangiectases^[11], and they also form in the lining of the nose and gut^[10]. These fragile vessels bleed easily, and nosebleeds are very common in people with HHT^[11].

After a vessel bleeds, the body seals it with a clot held together by a protein mesh called fibrin. A protein called plasmin dissolves fibrin, and plasmin is made from plasminogen^[12]. Tranexamic acid, an older pill, slows this clot breakdown by blocking binding sites on plasminogen^[12], and doctors already use antifibrinolytic drugs of this kind off label for HHT bleeding, according to the PATH-HHT researchers^[10].

ALN-6400 takes a different route to the same pathway. Alnylam describes it as an RNAi therapeutic targeting plasminogen and its approach as hepatic plasminogen lowering, meaning it aims to reduce how much plasminogen the liver makes^[5][8]. The idea is that clots could last longer at bleeding sites. Alnylam reported in July 2026 that in UK Biobank data, low natural plasminogen levels were not linked to a higher risk of heart attack, ischemic stroke or clots in arteries^[9].

That analysis looked at people's natural levels and did not test the drug. Whether ALN-6400 reduces bleeding in people with HHT is what the InsigHHT study is testing^[1].

InsigHHT (NCT06659640) is a Phase 1/2, randomized, double-blind, placebo-controlled study in 2 parts^[1]. Part A gave adult healthy volunteers a single dose of ALN-6400 or a placebo. Part B gives adults 18 and older with a clinical diagnosis of HHT multiple doses of ALN-6400 or a placebo^[1]. The study enrolled 89 people across both parts and is listed as active but no longer recruiting^[1].

The study began on November 7, 2024 and lists an estimated primary completion of January 5, 2028^[1]. It lists 16 sites, 8 of them in the US (Birmingham in Alabama, Cypress in California, Gainesville in Florida, Indianapolis, Boston, Rochester in Minnesota, St Louis and Chapel Hill in North Carolina), with others in Australia, Canada, France, Germany and Spain^[1].

Alnylam said on October 29, 2026 that it expects to announce Phase 2 HHT data in conjunction with its fourth quarter and full year 2026 earnings call in February 2027^[4].

ALN-6400 is also in HMBeacon (NCT07575308), a Phase 2 study in females aged 16 to 45 with von Willebrand disease and heavy menstrual bleeding^[2]. HMBeacon has no placebo group. It compares 2 ALN-6400 treatment groups, measures side effects up to week 72 and began on July 30, 2026^[2].

ClinicalTrials.gov lists InsigHHT as starting on November 7, 2024^[1], and Alnylam's February 2025 results release said it had initiated Phase 1 studies of ALN-6400 for a bleeding disorder^[6]. In June 2025 Alnylam presented UK Biobank analyses and animal data on lowering plasminogen in the liver at the European Hematology Association congress^[8].

In July 2026 it presented a further UK Biobank analysis of plasminogen levels at the International Society on Thrombosis and Haemostasis congress^[9]. Alnylam reported on July 30, 2026 that it had started the Phase 2 von Willebrand disease study^[5]. On October 29, 2026 it said the healthy volunteer data would be shared in December 2026 and the HHT Phase 2 data in February 2027^[4].