BIIB122 / DNL151 (LUMA)

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Biogen and Denali Therapeutics (Denali discovered the drug; Biogen shared development). Results announced 21 May 2026 and presented in full at the 2026 International Congress of Parkinson's Disease and Movement Disorders in Seoul (reported 5 Oct 2026).

What happened

Mutations in the LRRK2 gene make its enzyme overactive (landmark 7). BIIB122 is a tablet that blocks that enzyme. The bet was that lowering LRRK2 activity might help even people without a LRRK2 mutation, since the enzyme may be overactive in other forms of the disease.

• Design. Phase 2b, double-blind, placebo-controlled. 648 people aged 30–80 with early Parkinson's (Hoehn and Yahr stage I–II, diagnosed within 2 years), at 206 sites in 5 countries (NeurologyLive; the registry lists 113 locations). The registry shows it started 19 Apr 2022, with primary completion on 9 Mar 2026. People with or without a pathogenic LRRK2 variant could join. Dose 225 mg once daily; treatment for at least 48 and up to 144 weeks.
• Main measure. Time to confirmed worsening of 6 or more points on a combined MDS-UPDRS Part II + III score. Result: hazard ratio 1.04 (95% CI 0.85–1.28, p=0.4538), no benefit. Secondary measures also showed none.
• Target hit. LRRK2 phosphorylation (pS935) in blood fell by over 90% and a urine lysosomal marker (BMP) by about 50%, both by week 48. In a spinal-fluid sub-study of 86 people, a marker of LRRK2 activity (phosphorylated Rab10) fell by only about 30% at peak (week 24), hinting that less reached the brain.
• Safety. Serious adverse events 11.5% versus 11.9% on placebo. Stopping because of adverse events: 11.2% versus 4.6%. Headache 17.1% versus 9.2%.
• After LUMA. Biogen and Denali ended development in idiopathic Parkinson's (Biogen/Denali release, 21 May 2026). Denali continues the separate Phase 2a BEACON study in LRRK2 carriers (safety, drug levels and lysosomal biomarkers), with data expected in the first half of 2027. No separate efficacy results for carriers inside LUMA were reported.
• LIGHTHOUSE (Phase 3, LRRK2 carriers only; NCT05418673). A separate Phase 3 of the same drug, in early Parkinson's with a LRRK2 variant, started on 26 August 2022 and was terminated on 27 July 2023 by "sponsor decision". Only 7 people were enrolled (4 on BIIB122, 3 on placebo), and none finished. Because it stopped so early, it gave no usable efficacy answer for carriers.

Why it moved us toward a cure

The earlier inhibitor DNL201 had shown target engagement in people (landmark 200). LRRK2 activity had been reported to be raised in ordinary Parkinson's, not only in carriers (landmark 198). It is the first large, well-powered test of whether hitting a genetic target in the general Parkinson's population can slow the disease. The answer was no, even with clear target engagement. That is a strong warning that biomarker success is not clinical success, and that precision trials in people with the mutation are the logical next step.

The drug's Phase 1 and 1b studies are in landmark 229.

Target engagement was read with blood and urine LRRK2 markers (landmark 231).

Outcome

Dead end in broad early Parkinson's. The idea stays open in LRRK2 carriers (BEACON, due first half of 2027), which is the group where the gene is the cause. A reason it may have failed: the spinal-fluid target hit was modest.

Sources

• Biogen/Denali release, 21 May 2026 (BioSpace) · Biogen investor release
• NeurologyLive, 5 Oct 2026, full data · Parkinson Canada commentary
• ClinicalTrials.gov NCT05418673 (LIGHTHOUSE) (status, dates and enrolment read from the registry record, including the results participant flow)
• LUMA registry record: NCT05348785 (650 enrolled; the 648 randomised figure is from the sponsors).
• Not yet verified: the reason behind LIGHTHOUSE's "sponsor decision" (Biogen announced the stop on 5 Jun 2023 per BioPharma Dive; the registry gives no detail); a peer-reviewed LUMA paper; any release newer than the October 2026 presentation; how many carriers were in LUMA; BEACON enrolment; the earlier claim that about 80% had never taken symptom treatment (removed, not found in the sources read).