• Repeated immunisation with PD01A is safe and well-tolerated over an extended time period
• Active immunisation with PD01A resulted in a substantial aSyn-specific antibody response and memory effect
• This antibody response was associated with a substantial reduction in CSF oligomeric aSyn protein
• Results represent long-term data from a first-in-human study series using specific active immunotherapy (SAIT) AFFITOPE® PD01A

VIENNA, AUSTRIA - EQS Newswire - June 22, 2020 - AFFiRiS AG, a clinical-stage biotechnology company developing novel disease-modifying specific active immunotherapies (SAITs), today announced that detailed results of the phase 1 clinical program with its lead candidate PD01 in early Parkinson's disease (PD) patients were published in the peer-reviewed journal The Lancet Neurology (https://doi.org/10.1016/S1474-4422(20)30136-8). The results of the long-term phase 1 trial series demonstrated that repeated immunisation with PD01A is safe and well-tolerated over an extended period of time. The data showed that active immunisation with PD01A leads to a positive antibody response specific for alpha-synuclein (aSyn), a protein that is believed to contribute to the pathogenesis of Parkinson's disease. Active immunisation also resulted in a substantial reduction (mean of 51%) in the levels of aSyn oligomers in the CSF of patients who received the high dose therapy, which is interpreted as a sign of in vivo target engagement.

Extensive evidences support the role of soluble aSyn oligomers as a causative factor in the development of Parkinson's disease and reducing the levels of aSyn oligomers could potentially have disease-modifying benefit in PD patients.

In the trial, the patients were randomised to receive four immunisations with two different doses of AFFiRiS' drug candidate and were followed for at least 3.5 years to assess the safety of the PD01A immunotherapeutic. In particular, this was the first study to assess the feasibility and safety of a specific active immunotherapy against aSyn.

The results of this phase 1 study demonstrated that immunisation with PD01A is safe when repeatedly administered and was well-tolerated over an extended time period. With the exception of expected local injection site reactions, most AEs were considered unrelated to study treatment. No patient discontinued due to treatment emergent adverse events. Immunisation resulted in a significant increase in IgG antibody against the immunizing AFFITOPE® PD01 peptide already after three priming injections with a maximum titre being achieved at Week 12. This led to a specific humoral immune response against the aSyn target epitope. Moreover, the priming immunisations resulted in a substantial memory effect for the aSyn target epitope as evidenced by the reactivation and augmentation of the antibody response following booster immunizations. This resulted in the persistence of the immune response until study end.

Although the study was not designed and not powered to evaluate clinical efficacy, clinical signals of efficacy were observed. In particular, MDS-UPDRS motor scores were generally stable across the study series, in contrast to published data which reports a worsening in MDS-UPDRS scores in a similar patient population.

"The PD01A safety profile and the substantial sustained aSyn antibody response targeting both the toxic oligomeric and fibrillar form of aSyn, which are believed to contribute to the pathology of PD, may offer a promising strategy for long-term management of PD, addressing an urgent medical need," said Dieter Volc MD, principal investigator of the study series and Head of the Parkinson Center at the Privatklinik Confraternitaet, Vienna.

"The encouraging results, including signals for clinical efficacy, warrant the further development of our drug for the treatment of PD in a phase 2 clinical trial," commented Noel Barrett, Ph.D., AFFiRiS's Chief Executive Officer. "Potentially, specific active immunization approaches such as with PD01A might overcome the limitations of passive antibody infusion approaches for PD, caused by their short in vivo half-lives, and circumvent frequent and high treatment costs by stimulating a self-produced, long-lasting immune reaction."

The data published in Lancet Neurology is the first report of an active anti-aSyn immunotherapy associated with reduction of CSF aSyn oligomers in PD patients and points to the possible development of this protein as a potential biomarker for disease progression.

The phase 1 trial was supported by The Michael J. Fox Foundation for Parkinson's Research. A phase 2 trial in early-stage Parkinson's disease patients is in preparation and expected to start in the second half of 2020, depending on the emerging COVID-19 situation.

About the Phase 1 clinical trial study:

The study was a patient-blinded, single-centre, randomised, first-in-human study followed by three consecutive extensions. 24 Parkinson's disease patients were randomised to receive four immunisations with either 15μg or 75μg PD01A and were followed for at least 3.5 years. For the first booster injection, patients were re-randomised to receive PD01A doses of 15μg or 75μg. All patients received a second booster injection of 75μg. The primary objective was to assess the safety of the PD01A immunotherapeutic. These studies were registered at EudraCT (2011-002650-31, 2013-001774-20, 2014-002489-54 and 2015-004854-16). 

About AFFITOPE® PD01:

AFFITOPE® PD01 is AFFiRiS' novel immunotherapy candidate for the treatment of early-stage Parkinson's disease patients. PD01 is a synthetically produced alpha-synuclein (aSyn)-mimicking peptide-based specific active immunotherapy (SAIT), identified by the AFFiRiS' AFFITOME® technology, that targets the protein aSyn. This protein has been identified as playing a key role in the onset and progression of Parkinson's disease.

About Parkinson's disease:

Parkinson´s disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease and the most common neurodegenerative movement disease.  It affects approximately 1% of the population above the age of 60, about 7-10 million people worldwide. PD is a chronic progressive disorder, defined by a combination of motoric and non-motoric syndromes. The hallmark of the disease is a substantial loss of dopaminergic neurons in the brain accompanied by accumulations of filamentous protein inclusions predominantly composed of alpha Synuclein (aSyn). Evidence suggests that the misfolding of the aSyn protein causes inflammation, synaptic dysfunction and finally neuronal cell death. Current therapies target symptoms but fail to modify the underlying neurodegeneration. In addition, these therapies result in varying degrees of side effects, and their beneficial effects diminish over time.