FDA fast-tracks experimental vaccine aiming to slow early Parkinson’s

The U.S. Food and Drug Administration (FDA) has awarded fast-track designation — a status that aims to speed the development of promising treatments for serious conditions — to a Swiss biopharmaceutical company for an experimental vaccine designed to slow or prevent neurodegeneration in people with early Parkinson’s disease.

The regulatory agency also cleared an investigational new drug (IND) application from the developer, AC Immune, which will allow an ongoing clinical trial of the vaccine candidate, called ACI-7104, to expand to sites in the U.S. That Phase 2 trial, dubbed VacSYn (NCT06015841), is now underway at 12 locations in Europe.

The granting of fast-track status was supported by interim trial results showing that ACI-7104 was safe and well tolerated, and triggered an immune response in all treated patients. The findings also provided early signals of activity, according to the developer.

AC Immune expects to report full results from the first part of the trial, covering about two years of treatment, in the second half of 2026, according to a company press release providing updates on the experimental vaccine.

“Fast Track designation and IND clearance from the FDA are important achievements for ACI-7104 … given its potential to address the significant unmet need in Parkinson’s,” said Martin Zügel, MD, AC Immune’s interim CEO. “We look forward to working closely with the FDA as we advance ACI-7104 through its ongoing clinical development [toward] potentially delivering a much-needed treatment option for patients.”

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Parkinson’s is caused by the progressive loss of dopaminergic neurons, which are nerve cells that produce dopamine, a signaling molecule involved in movement control. Clumps of misfolded alpha-synuclein protein are believed to contribute to neuron damage and disease progression.

ACI-7104 is an optimized version of an earlier experimental vaccine, called Affitope PD01A, that was originally developed by Affiris and later acquired by AC Immune.

Experimental Parkinson’s vaccine targets toxic protein clumps

This newer version is an active immunotherapy that uses a lab-made small protein similar to alpha-synuclein to train the immune system to produce antibodies that recognize toxic forms of the protein.

By targeting these abnormal protein clumps, or aggregates, ACI-7104 is intended to help the body clear alpha-synuclein, potentially preventing its further accumulation and spread. The goal is to ultimately slow or prevent Parkinson’s progression.

In earlier clinical studies, ACI-7104 was generally well tolerated, with no treatment-related serious adverse events or treatment discontinuations reported.

The experimental vaccine elicited antibodies against alpha-synuclein, detected in both blood and cerebrospinal fluid (CSF), the fluid that surrounds the brain and spinal cord.

Among those receiving a higher dose, CSF alpha-synuclein aggregate levels decreased by 51% after the initial treatment, suggesting that the induced antibodies were reaching and interacting with their intended target.

The ongoing VacSYn trial is evaluating the safety and tolerability of ACI-7104 in an estimated 150 adults with early Parkinson’s. The study, being conducted in Germany, Spain, and the United Kingdom, is also assessing both immune responses and the biological effects of the injection treatment among participants, who range in age from 40 to 75.

In the first part of the trial, 34 participants — 65% of them men, and with a mean overall age of 62.1 — were randomly assigned to receive ACI-7104 or a placebo for 18 months, or about 1.5 years, followed by a six-month follow-up period. Participants had been diagnosed with Parkinson’s for a median of 10.3 months, and most (68%) were receiving levodopa (L-DOPA), a mainstay treatment for Parkinson’s, at a 300 mg daily dose.

The treatment was administered via intramuscular, or into-the-muscle, injections, given at the study’s start and at one, three, and six months, and again at one and 1.5 years. 

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Developer granted $4M for VacSYn trial studies

Results recently shared by the company demonstrated that ACI-7104 was generally safe and well tolerated, with no reported serious adverse events related to the treatment. The most common adverse events were injection site reactions, affecting 56% of participants, headaches, seen for 15%, and fatigue, affecting 12%; these events were generally transient and mild in severity.

All participants developed antibodies against aggregated alpha-synuclein, with antibody levels increasing after each treatment dose.

The developer recently announced a $4 million research grant from the Vijay and Marie Goradia Charitable Foundation in Texas. That funding will support the evaluation of ACI-7104’s long-term safety and effectiveness for an additional two years in the first part of the VacSYn trial, according to the company.

In its second part, researchers will assess changes in motor and nonmotor symptoms of Parkinson’s, measured with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale and digital biomarkers. Changes in dopamine transporter levels and brain function, blood flow, and microstructure will also be evaluated using advanced imaging techniques, per the company.

Günther Staffler, PhD, AC Immune’s executive vice president of development, said “ACI-7104 represents a promising active immunotherapy designed to target [disease-causing alpha-synuclein] a-syn for the treatment of … early [Parkinson’s disease].” According to Staffler, “the FDA’s decision signifies the growing importance of the program including the positive interim Phase 2 findings.”