Alnylam enters obesity with ALN-6222, a first-in-human subcutaneous siRNA — the first RNAi-modality asset in the scope — alongside Phase 3 → COMPLETED transitions for Lilly's retatrutide (n=2335) and AstraZeneca's AZD9550 + AZD6234 dual combination. — 6 trials with material updates.

Competitive Intelligence · Obesity and Type 2 Diabetes

Thursday, June 4, 2026

Alnylam enters obesity with ALN-6222, a first-in-human subcutaneous siRNA — the first RNAi-modality asset in the scope — alongside Phase 3 → COMPLETED transitions for Lilly's retatrutide (n=2335) and AstraZeneca's AZD9550 + AZD6234 dual combination.

Key Signals · 6 trials updated

  • Alnylam Pharmaceuticals NCT07624071 — ALN-6222, a subcutaneous siRNA/RNAi therapeutic, registered as a Phase 1 first-in-human SAD study in obesity (n=88, NOT_YET_RECRUITING, single Canadian site). Novel modality and new sponsor for the franchise; added to priority_sponsors + tracked_molecules this cycle.
  • Eli Lilly NCT05929066 — retatrutide (GLP-1/GIP/glucagon triple agonist) Phase 3 in obesity/overweight, n=2335, marked COMPLETED (primary completion 2026-04-06). Pivotal readout pending.
  • Eli Lilly NCT06584916 — orforglipron ATTAIN-MAINTAIN Phase 3 weight-maintenance trial (n=376) marked COMPLETED (primary completion 2025-11-21). First oral GLP-1 maintenance readout.
  • AstraZeneca NCT06862791 — AZD9550 + AZD6234 fixed-combination Phase 2 (n=377) marked COMPLETED. First material AZ signal in dual-MOA obesity combo; supports the co-agonist combination thesis from a tracked sponsor.
  • Novo Nordisk NCT05813912 — insulin icodec + semaglutide Phase 3 in T2D (n=148) marked COMPLETED (primary completion 2025-04-14).
  • Scope-hygiene: Novo NNC0113-5840 (NCT07566390) and NNC0497-0040 (NCT07578584) remain pending addition to tracked_molecules; new GLP-1 Phase 3 head-to-head Bofanglutide/GZR18 vs semaglutide (NCT07622810, Carnot Labs) flagged for sponsor-watch consideration.

Material updates (last 24h, LastUpdatePostDate 2026-06-03 / 2026-06-04)

> Re-scan note: this report supersedes the earlier 2026-06-04 run (prompt_sha f8ca428e6d80). Scope was widened to add Alnylam Pharmaceuticals to priority_sponsors, ALN-6222 to tracked_molecules, and "siRNA / RNAi therapeutics for obesity" to mechanisms. The dedicated RNAi pass returned exactly one trial in-window — NCT07624071 — confirming the new scope is live.

New registration — novel modality (priority sponsor, any phase)

  • NCT07624071 — A Study to Evaluate ALN-6222 in Participants With Obesity (Alnylam Pharmaceuticals, Phase 1, n=88). StudyFirstPost 2026-06-03 (genuine first registry posting), NOT_YET_RECRUITING, estimated start 2026-06-03, primary completion 2027-12-14. Randomized, triple-blind, placebo-controlled single-ascending-dose (SAD) first-in-human; subcutaneous siRNA / RNAi therapeutic (keyword-tagged "siRNA, RNAi therapeutic"). BMI 30–<40, HbA1c <6.5%, single site in Mount Royal, Canada. This is the first RNAi-modality asset and first Alnylam program to enter the obesity scope — a mechanistically distinct entrant from the incretin/amylin peptide field. The undisclosed target is the key open question; secondary outcomes track plasma protein-marker changes (PD readthrough to the silenced target). Recommend a follow-up pull when results post or when a target/MOA disclosure appears.

Phase 3 status → COMPLETED

  • NCT05929066 — Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight (Eli Lilly, Phase 3, n=2335). PrimaryCompletion 2026-04-06, statusVerified 2026-06. Largest retatrutide obesity Phase 3 — readout will set the benchmark for the GLP-1/GIP/glucagon triple-agonist class. Watch for Lilly press release / ADA-window disclosure.
  • NCT06584916 — Orforglipron ATTAIN-MAINTAIN (Eli Lilly, Phase 3, n=376). PrimaryCompletion 2025-11-21, statusVerified 2026-06. First Phase 3 weight-maintenance trial for an oral small-molecule GLP-1RA — directly addresses the post-discontinuation rebound narrative.
  • NCT05813912 — Insulin Icodec + Semaglutide in T2D (Novo Nordisk, Phase 3, n=148). PrimaryCompletion 2025-04-14, statusVerified 2026-05. Combination weekly-basal + GLP-1 study; supports IcoSema positioning.

Phase 2 status → COMPLETED (tracked sponsor, dual-MOA combination)

  • NCT06862791 — AZD9550 + AZD6234 weight-loss combination Phase 2 (AstraZeneca, n=377). PrimaryCompletion 2026-05-11. First material competitive-intelligence signal from AstraZeneca in scope this cycle — a co-administration Phase 2 of AZ's GLP-1/glucagon (AZD9550) with AZD6234 (long-acting amylin), placebo-controlled with each monotherapy arm. Read-through to combo regimens (cagrilintide+sema, eloralintide+macupatide). Pull full results when hasResults flips.

Recruiting Phase 3 with LastUpdatePostDate bump (likely site/contact updates — NOISE)

Lilly's eloralintide Phase 3 cluster (NCT07282600, NCT07321886, NCT07353931, NCT07369011, NCT07392190), retatrutide NCT07357415, orforglipron NCT07153471 / NCT07202884 / NCT06672939, and tirzepatide SURMOUNT-ADOLESCENTS-2 NCT06439277 all had LastUpdatePostDate=2026-06-03/04 with no PCD/SCD/status delta visible at the search-record level. Treating as administrative until a status-history diff suggests otherwise.

Amgen's MariTide trials NCT07226765 (OSA Phase 3) and NCT07441252 (elevated liver fat Phase 2) — recruiting updates, no status transition. Hold.

Scope hygiene proposals

  • NNC0113-5840 — NCT07566390, Phase 1 obesity/overweight, n=48, Novo Nordisk A/S (registered 2026-05-05). Net-new NNC code; propose adding to tracked_molecules.
  • NNC0497-0040 — NCT07578584, Phase 1 healthy / overweight / T1D+overweight, n=146 (registered 2026-05-11). Propose adding to tracked_molecules.
  • Bofanglutide (GZR18) — NCT07622810 BALANCE-OBS, Phase 3 head-to-head vs semaglutide in Latin American adults (Carnot Laboratories, n=352, first post 2026-06-03). GLP-1 mechanism match but sponsor is not currently tracked; an active semaglutide comparator makes it worth a sponsor-watch decision rather than a silent add.
  • HS-20094 (Hansoh) completions NCT06118021 (Ph2) / NCT06839664 (Ph3) flipped to COMPLETED in-window; Hansoh is not a tracked sponsor (distinct from Hanmi). Note for awareness, no action.

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