PD01A synuclein vaccine (AFFiRiS)

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

Dieter Volc (Vienna), Werner Poewe and colleagues; sponsor AFFiRiS AG, Vienna; funded with the Michael J Fox Foundation. Lancet Neurology 2020;19:591–600. NCT01568099.

What happened

• Design. Phase 1, single private clinic in Vienna. 32 people aged 45 to 65 with early Parkinson's (up to 4 years since diagnosis, Hoehn and Yahr 1 to 2) were recruited between 14 Feb 2012 and 6 Feb 2013. 24 were randomised 1:1 to four injections under the skin, four weeks apart, of 15 or 75 micrograms of PD01A, masked to dose; the registry and Alzforum describe the other 8 as an untreated comparison group, which the paper's abstract does not mention. Follow-up was extended with a first booster (15 or 75 micrograms, randomised) and a second booster (75 micrograms), giving 221 to 259 weeks in the study (follow-up registry entries NCT01885494, NCT02216188, NCT02618941).
• Safety. All patients had at least one adverse event, mostly unrelated to treatment; transient injection-site reactions affected all but one. Systemic treatment-related events included fatigue (4), headache (3) and myalgia (3). Repeated MRI found no sign of inflammation. 21 of 24 (87%) received all six immunisations and completed the study; one was withdrawn after a change of diagnosis to multiple system atrophy.
• Immune response. Antibody titres against the vaccine peptide rose from 1:46 to 1:3580 at week 12 (15 microgram group) and from 1:76 to 1:2462 (75 microgram group), returned to baseline over about two years, and were reactivated by boosters to as high as 1:20218. The paper reports target engagement; Alzforum says 23 of 24 responded.
• Spinal fluid (Alzforum). In a post hoc look (decided after seeing data), oligomeric alpha-synuclein fell by about 51% after four 75 microgram doses. Total alpha-synuclein did not change. The trial's design (no placebo group, small size) cannot show an effect on the disease.
• Afterwards. PD01A and a sister vaccine, PD03A, were tried in multiple system atrophy from April 2017 (Phase 1; not part of this landmark). AFFiRiS announced a Phase 2 of PD01A in January 2020, but none was registered.

Why it moved us toward a cure

It showed that active immunisation against alpha-synuclein is feasible in humans: the body can make the antibody itself, which could be cheaper and longer lasting than the repeated antibody infusions in landmark 63. It tested the 2005 mouse idea in landmark 103. The UB-312 vaccine followed (landmark 183).

Outcome

Advanced as a safety and immune-response result only. AC Immune bought the PD01 programme in July 2021 and developed ACI-7104 from it (landmark 325).

Sources

• Volc et al., Lancet Neurol 2020;19(7):591–600, DOI 10.1016/S1474-4422(20)30136-8, PMID 32562684 (abstract read via Europe PMC) (AFFiRiS release via LISAvienna)
• Alzforum therapeutics page, ACI-7104 / PD01A
• ClinicalTrials.gov NCT01568099 (start Feb 2012, enrolment 32, single-blind randomised, completed May 2014 for the main phase; read 19 Oct 2026)
• AC Immune acquisition, Biopharma-Reporter, 27 Jul 2021
• Not yet verified: the paper's full text (the 23-of-24 responder count, the 51% spinal-fluid fall and the untreated comparison group rest on Alzforum and the registry); motor results; the 15 microgram CSF result.