Results Set Stage for Phase 2 Trial of Investigational Vaccine Affitope PD01A, Affiris Says

Multiple administrations of Affitope PD01A, an investigational vaccine for Parkinson’s disease, elicit a safe and sustained immune response against alpha-synuclein — a protein involved in the development of Parkinson’s — in patients at the early stages of the disease, according to results from a Phase 1 clinical program.

Trial findings were reported in the study, “Safety and immunogenicity of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson’s disease: a randomised, single-blinded, phase 1 trial,” published in The Lancet Neurology.

A distinctive feature of Parkinson’s is the progressive degeneration of brain cells due to the accumulation of toxic clumps of the protein alpha-synuclein, called Lewy bodies.

Affitope PD01A is an experimental vaccine being developed by Austrian biotech company Affiris to treat Parkinson’s. It works by prompting a patients’ immune system to produce antibodies against a man-made peptide that is very similar to alpha-synuclein.

Preclinical studies in two mouse models of Parkinson’s have shown that Affitope PD01A lowered the number of alpha-synuclein aggregates found in the animals’ brains, improved their memory, and alleviated motor impairments.

Based on these promising findings, Affitope PD01A advanced to clinical testing in a Phase 1 clinical program.

The clinical program consisted of the first-in-human randomized Phase 1 trial of Affitope PD01A (NCT01568099), followed by three extension studies (NCT01885494; NCT02216188; NCT02618941).

During the first trial, patients aged 45–65 with early-stage Parkinson’s were assigned randomly to receive four under-the-skin (subcutaneous) injections of Affitope PD01A at a dose of 15 or 75 micrograms (mcg) on their upper arm, once every four weeks.

Study participants then were enrolled in the first extension study and initially monitored for a period of 52 weeks (approximately one year), followed by an additional period of 39 weeks (approximately 10 months).

After that, patients were divided randomly into two dose groups (15 or 75 mcg) to receive the first booster vaccine immunization, and followed for 24 weeks (six months). All patients received a second booster immunization of Affitope PD01A at a dose of 75 mcg and were monitored for an additional 52 weeks.

Of note, a booster is an extra administration of a vaccine after the first exposure dose, which allows the body to increase its immunity when the initial vaccine starts to wear off.

Researchers now reported the findings of the entire Phase 1 clinical program of Affitope PD01A.

A total of 32 patients with early Parkinson’s were recruited from February  2012 to February 2013 to participate in the first Phase 1 trial of Affitope PD01A. From these, 24 were eligible to participate in the study, and were assigned randomly to one of the two dose groups to receive four immunizations of the vaccine.

Three patients withdrew from the program, and the remaining 21 (87%) received all six vaccine immunizations.

Repeated administrations of Affitope PD01A led to a significant increase in the levels of antibodies targeting alpha-synuclein, which reached a maximum value at week 12, after patients had received three immunizations.

This increase in the levels of antibodies against alpha-synuclein allowed the patients’ immune system to mount a specific immune response against the protein.

In patients receiving the highest dose of the vaccine, the levels of alpha-synuclein aggregates found on their cerebrospinal fluid (CSF, the fluid that surrounds the brain and spinal cord) dropped by 51%, confirming successful target engagement of the newly formed antibodies to alpha-synuclein.

Antibody levels began to drop over the first two years of the program, but rapidly rose in response to booster immunizations, confirming the first vaccine administrations successfully imprinted a memory effect in the patients’ immune systems. This allowed patients to maintain a continuous immune response against alpha-synuclein until the end of the program.

Repeated vaccine immunizations also were found to be safe and well-tolerated over the entire duration of the program.

All patients experienced at least one adverse event (side effect) during the trials, but most of them were found to be unrelated to treatment. None of the study participants discontinued treatment due to adverse events.

The most common treatment-related adverse events included fatigue, headaches, muscle pain, muscle rigidity, and tremor.

“The PD01A safety profile and the substantial sustained aSyn [alpha-synuclein] antibody response targeting both the toxic oligomeric and fibrillar form of aSyn, which are believed to contribute to the pathology of PD [Parkinson’s disease], may offer a promising strategy for long-term management of PD, addressing an urgent medical need,” Dieter Volc, MD, said in a press release. Volc is principal investigator of the study series and head of the Parkinson Center at the Privatklinik Confraternitaet, Vienna.

“The safety profile and positive antibody response of PD01A supports the further development of this immunotherapeutic for the treatment of Parkinson’s disease in a phase 2 clinical trial,” the researchers wrote.

The company expects to start the Phase 2 trial later this year.