Prasinezumab: PASADENA and PADOVA

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

Roche/Genentech (with Prothena, the drug's originator). First authors: Gennaro Pagano (PASADENA, NEJM 2022) and Tatiana Nikolcheva (PADOVA, The Lancet 2026); Pagano's author list also includes Tanya Simuni and Kenneth Marek.

What happened

• PASADENA (Phase 2, 316 people, early Parkinson's, untreated or on a stable MAO-B inhibitor): placebo, 1,500 mg or 4,500 mg by infusion every 4 weeks for 52 weeks (105, 105 and 106 people). Change in the combined MDS-UPDRS score (parts I-III) was 9.4 on placebo against 7.4 (1,500 mg; P=0.24) and 8.8 (4,500 mg; P=0.72). Dopamine-transporter scans did not differ. Infusion reactions occurred in 19% and 34% of the drug groups.
• A 2024 Nature Medicine analysis of subgroups (exploratory, after the fact) found slower motor progression in faster-progressing groups, for example people on MAO-B inhibitors at baseline.
• PADOVA (Phase 2b, 586 people aged 50-85 on stable levodopa or MAO-B inhibitor, 1,500 mg vs placebo every 4 weeks, at least 76 weeks): time to confirmed motor worsening (a 5-point rise in off-medication part III) had a hazard ratio of 0.84 (95% CI 0.69-1.01; p = 0.066); median 61.1 vs 49.7 weeks. Serious adverse events were 12% in each group. The paper calls its exploratory evidence a sign of clinical activity.
• Roche announced Phase 3 on 15 June 2025. PARAISO (NCT07174310) began 24 Nov 2025: 900 planned, primary completion estimated June 2029 (registry updated 6 Oct 2026, recruiting).

Why it moved us toward a cure

Prasinezumab is the humanised form of the mouse antibody 9E4 (landmark 204); the 2011 mouse paper on 9E4 was retracted in November 2024 over image concerns, so the preclinical case now rests on the human trials. It is the best-supported test of the idea behind landmarks 5 and 8: if synuclein spreads from cell to cell, an antibody might stop it.

Outcome

Open. Two Phase 2 trials missed their primary endpoints; Phase 3 is recruiting. PADOVA's registry entry shows its follow-up running to an estimated June 2031. Compare the failed antibody in landmark 64.

Sources

• Pagano et al., N Engl J Med 2022;387:421–432, DOI 10.1056/NEJMoa2202867
• Pagano et al., Nat Med 2024;30:1096–1103, DOI 10.1038/s41591-024-02886-y
• Nikolcheva et al., Lancet 2026;407:2227–2240, DOI 10.1016/S0140-6736(26)00865-2 · PADOVA registry
• Genentech release, 15 Jun 2025 · PARAISO registry
• Not yet verified: the levodopa-subgroup hazard ratio of 0.79 and the 75% share (removed from the text); the Phase 1 data; which part of synuclein the antibody binds (sources say only "aggregated alpha-synuclein"); the full text of the Lancet paper (abstract read). PASADENA's registry number is NCT03100149. Both trials are registered as Phase 2 (316 and 586 enrolled, API 22 Oct 2026); the frontmatter has no n because the file covers two trials.