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AFFiRiS Announces Encouraging Long-term Data from a Series of First-in-Human Studies Using AFFITOPE® PD01A Targeting Oligomeric Alpha-synuclein in Early Parkinson's Disease Patients

AFFiRiS AG, a pharmaceutical company developing specific active immunotherapies (SAITs) for treatment of neurodegenerative diseases, announces results of their first-in-human series of studies with AFFITOPE® PD01A. In a randomized, parallel group, single-center setting, tolerability and safety of repeated subcutaneous (s.c.) administration of two doses of AFFITOPE® PD01A formulated with adjuvant to patients with early Parkinson's disease (PD) were assessed.

The studies were conducted at Confraternität by Principal Investigator Prim. Dr. Dieter Volc and were funded by a series of grants from The Michael J. Fox Foundation for Parkinson's Research totaling nearly $3.5 million as well as a €1.4 million government-funded loan by the government agency AWS in Austria ("Austria Wirtschaftsservice"). AFFITOPE® PD01A is a synthetically produced alpha-synuclein (aSyn)-mimicking peptide specific active immunotherapy. In the AFF008 study series (a series of four consecutive studies), 24 patients were randomized to either AFFITOPE® PD01A low dose (15 µg) or high dose (75µg). Patients received six injections: four for priming immunizations every four weeks, and the 5th and 6th as "boost" and "reboost" immunizations (appr. 2.2 years and 3 years, respectively after the first immunization). Key objectives were to show safety and tolerability as well as immunogenicity of AFFITOPE® PD01A in a long-term outpatient treatment setting.

Summary of Key Results:

The data presented at the AAT-ADPD Focus Meeting on March 17, 2018, by Prof. Werner Poewe are from the pilot first-in-human study series in patients with early PD treated over a period of up to four years. A total of 32 patients was enrolled, 24 of them receiving active treatment and 8 PD patients on standard of care medication, who served as an observational comparison group. 21 patients in the PD01A treatment groups and five in the observational group completed the entire series of studies. At screening, the average time of PD after first diagnosis was 2.6 years. Patients were allowed to continue their standard of care PD medication.

Safety and Tolerability:

Both doses of AFFITOPE® PD01A were locally and systemically well tolerated.  No study drug-related serious adverse events (SAE) or suspected unexpected serious adverse reactions (SUSAR) occurred. No other safety signals (including data from imaging and safety lab) were reported. Systemic adverse events (AEs), standardized by the number of observed patients, resulted in 11.1 systemic AE/subject receiving AFFITOPE® PD01A versus 10.3 systemic AE/subject in the observational arm, indicating that the systemic effects of PD01A on safety were very similar to that in patients on standard of care treatment. The majority of adverse events, approximately 55%, were local reactions (LRs), the great majority of LRs being only mild and without dose dependency.

Immunogenic Profile & Clinical Scores:

AFFITOPE® PD01A showed a clear immune response against the peptide itself and cross-reactivity against aSyn targeted epitope over time. The first boost immunization produced a significant effect on all analyzed titers, resulting in the maximum titers observed in this series of studies. The second boost immunization further stabilized the produced antibody titers. Thus, a significant increase in titers against PD01A was seen over time, which translated into a humoral immune response against aSyn, being approximately one order of magnitude lower. In addition, PD01-specific antibodies were detectable in cerebrospinal fluid. Clinical scores for PD were stable during the entire study period, however, the study was not designed and not powered to evaluate clinical efficacy.

Data from post-hoc analyses indicate that AFFITOPE® PD01-induced antibodies preferentially bind to both oligomeric and fibrillar aSynwhen compared with its monomers and showed that there was a trend in reduction of oligomeric aSYN levels in plasma as well as cerebrospinal fluid upon treatment with PD01A at week 26. "Immunogenicity results after 4 years of treatment are encouraging and support the hypothesis that long-term disease management by targeting aSyn, a protein that is believed to contribute to the pathogenesis of Parkinson's disease, with active immunotherapy seems to be feasible," stated Prof. Werner Poewe, Chairman of the Department of Neurology at the Medical University Innsbruck, Austria, and leading PD expert. "Future trials should focus on how to translate the immune response seen in these series of studies into clinical efficacy."

"The results of the AFF008 study series are strong encouragement for us to continue development of PD01. We have in parallel optimized the formulation of PD01 and immunization schedule for future clinical development in order to improve immunogenicity even more. Parkinson's is a debilitating disease which puts significant burden on patients and caregivers. They deserve our best shot at goal to bringing a potentially disease modifying therapy for long term disease management with our unique modality to patients." commented Oliver Siegel, CEO of AFFiRiS AG.