BIA 28-6156 (ACTIVATE) in GBA1 carriers

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

Bial (sponsor). The drug was earlier called LTI-291, and has the name pariceract. Bial announced topline results on 9 June 2026.

What happened

Variants in GBA1 are the commonest genetic risk factor for Parkinson's (landmark 16). They lower the activity of the enzyme GCase, which feeds a loop with alpha-synuclein (landmark 35). BIA 28-6156 is a daily pill meant to bind GCase and raise its activity. It is the opposite of venglustat, which cuts GCase's raw material (landmark 69).

• ACTIVATE (NCT05819359). Phase 2 (Bial calls it Phase 2b), randomised, placebo-controlled. 273 genetically confirmed GBA1 carriers, recruited over about 18 months at 85 sites in 11 countries in Europe and North America (Bial release). Registry: 10 mg or 60 mg a day, or placebo, up to week 78; started 31 March 2023. Main measure: time to clinically meaningful worsening on MDS-UPDRS Parts II and III.
• Result (2026). Bial's release says the study "did not meet its primary, nor the key secondary efficacy endpoints" and failed to slow progression versus placebo. It reported no unexpected safety concerns and ended development for this use. Bial plans publications and meeting talks; no numbers have been released.

Ownership. On 1 October 2020 BIAL set up a US affiliate, BIAL Biotech, in Cambridge, Massachusetts, and bought Lysosomal Therapeutics Inc. (LTI), taking over LTI-291 and its team; BIAL's release gave up to $130 million in possible payments (BIAL release, seen only in search snippets). MJFF had funded LTI's laboratory work testing candidates and assays for GCase levels (MJFF, 8 Oct 2020).

Why it moved us toward a cure

It is a large Phase 2 test of boosting GCase in people chosen by their genetics. Like venglustat, it was negative, so both ends of the pathway have now been tried in carriers. The enzyme is still a target for other drugs, such as ambroxol (landmark 40) and GT-02287 (landmark 234). Possible reasons for failure, which Bial has not confirmed: too little GCase rise, wrong stage of disease, or 18 months being too short.

Outcome

Dead end for BIA 28-6156 in GBA1-linked Parkinson's.

Sources

• Michael J. Fox Foundation, 10 Jun 2026
• Bial topline release, 9 Jun 2026 (Business Wire copy on ANSA) · European Biotechnology, 9 Jun 2026
• ClinicalTrials.gov NCT05819359 (read from the registry API on 19 Oct 2026; it still lists 237 planned, against 273 reported; last updated 13 May 2026)
• MJFF: biotech deal advances GBA therapy, 8 Oct 2020
• Alzforum: LTI-291
• Not yet verified: effect sizes; the safety numbers; the reasons for failure; whether the 237 versus 273 difference is a stale registry entry. As of 19 Oct 2026 the registry shows primary completion on 2 April 2026, status active, not recruiting, and no posted results, so the negative result rests on Bial's release (via a syndicated copy) and trade reports. The dose sentence above is from the registry, not the release.