•Reevaluation of primary and secondary endpoints confirms safety and tolerability and immunogenicity profile of long-term application over 4 years of AFFITOPE® PD01A
•Prof. Werner Poewe, Chairman of the Department of Neurology at the Medical University Innsbruck, Austria, and Leading PD Expert, Presented Results at a "Late Breaking Symposium on Treatment Strategies in PD" at the AAT-ADPD Focus Meeting in Turino, Italy on March 17
VIENNA, Austria, May 14, 2018 — 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 were 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 this 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.
About the AFF008 study series:
In the 4 consecutive studies AFFiRiS008, 008E, 008A and 008AA ("AFF008 study series"), 24 patients were randomized to receive four immunizations with either low dose (15 μg) or high dose (75 μg) AFFITOPE® PD01A in intervals of four weeks on an outpatient basis (study AFF008). To extend the observation period, an additional follow-up of twelve months was added (study AFF008E). In the third part of the study series (study AFF008A), a booster immunization was performed after rerandomizing patients from study AFF008E into two different doses of boost immunization (15 μg or 75 μg AFFITOPE® PD01A). In study AFF008AA ("reboost study"), a second booster with a fixed dose of 75 μg AFFITOPE® PD01A was applied to patients previously immunized five times. Key objectives were to show safety and tolerability as well as immunogenicity of AFFITOPE® PD01A in a long-term treatment setting.
About AFFITOPE® PD01A:
AFFITOPE® PD01A targets the protein aSyn, which plays a key role in the onset and progression of Parkinson''s Disease as well as Multiple System Atrophy (MSA), an orphan disease. AFFITOPE® PD01A is a specific active immunotherapy (SAIT) and one of two SAIT candidates currently being studied in phase I studies in both indications. So far, 98 PD and MSA patients have participated in studies investigating either AFFITOPE® PD01A or PD03A. During these phase I studies, patients were observed for up to 48 months (AFFITOPE® PD01A) or 12 months (AFFITOPE® PD03A), respectively, with regard to long-term safety, immunological and clinical parameters.
About AFFiRiS AG:
On the basis of its proprietary patented AFFITOME® technology, AFFiRiS develops preventative and therapeutic peptide specific active immunotherapies (SAIT) against chronic diseases. Its clinical pipeline consists of four SAIT candidates against PD, MSA and Atherosclerosis. Further SAIT candidates against Alzheimer as well as Huntington''s disease are in preclinical development. AFFiRiS has been able to attract funding of approx. € 165 Mio to date, half of which comes from license income and government grants. AFFiRiS is part of a consortium receiving funding from the European Union''s 7th Framework Programme under SYMPATH Grant Agreement No. 602999 (http://www.sympath-project.eu/) and MULTISYN Grant Agreement No. 602646 (http://www.multisyn.eu/). AFFiRiS currently employs 60 highly qualified staff at the Campus Vienna Biocenter in Vienna, Austria. www.affiris.com
About The Michael J. Fox Foundation for Parkinson''s Research:
As the world''s largest nonprofit funder of Parkinson''s research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson''s disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson''s patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $800 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson''s research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson''s disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson''s awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world. Learn more at www.michaeljfox.org.
Contact AFFiRiS AG:
Bettina Wessa
Karl-Farkas-Gasse 22
1030 Vienna, Austria
T +43 / (0)1 / 798 15 75 – 300
E bettina.wessa@affiris.com
W http://www.affiris.com
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PR&D – Public Relations for Research & Education
Ira Paschinger
Mariannengasse 8
1090 Vienna, Austria
T +43 / (0)1 / 505 70 44
E paschinger@prd.at
W http://www.prd.at
