Clinical safety, immunogenicity and efficacy of a therapeutic vaccine that combines peptides mimicking antigen receptors on autoimmune B and T cells associated with myasthenia gravis.
The MYASTERIX (2013 – 2018) project will advance a therapeutic vaccine candidate (designated orphan drug) indicated for myasthenia gravis (MG) to clinical proof of concept studies.
MG is a autoimmune disease caused by T cell dependent antibodies that bind to and deplete acetylcholine receptors (AChR) at neuromuscular junctions causing muscle weakness by interfering with neuromuscular transmission and junction architecture.
The vaccine candidate comprises two synthetic peptides designed to generate antibodies that bind to autoantibodies and T-cell receptors associated with MG.
These peptides prevented or improved muscle fatigue in a rat model of MG and increased the remission rate to 75% in pet dogs (compared to 17% natural remission rate in historical controls).
In both models, administration of the peptides resulted in reduced titres of anti-AChR antibodies and lower numbers of anti-AChR T-cells, based on the induction of antibodies that bound to the corresponding B and T cell antigen receptors.
These results suggest that similar antigen receptor mimetic vaccination approaches could drive autoimmune diseases like MG into long-term remission.
The objectives of the project are to manufacture toxicology and clinical batches of the vaccine human formulation based on already developed and tested standard operating procedures, to carry out stability and regulatory toxicity testing of the GMP product, to conduct phase I and subsequently phase II clinical trials to demonstrate safety, tolerability, and proof of mechanism of action/concept of the therapeutic vaccine.
The impact on MG patients will be to offer a targeted therapeutic approach requiring only three injections, bringing significant and lasting improvement, or even a cure.
MG is a model for many autoimmune diseases and the concept of targeted therapeutic vaccines could lead to a new class of drugs for the treatment of autoimmune diseases more generally, with a significant impact on innovation, competitiveness, and society.
The project partners are:
CuraVac Europe, (Belgium). A company specialized in therapeutic vaccines, sponsor of the clinical trials and scientific manager of the project.
UZA (Belgium). Antwerp University Hospital, Neurology Department, Prof. Rudy Mercelis team. UZA is a reference center of myasthenia gravis in Belgium.
LUMC (the Netherlands). Leiden University Medical Center, Neurology Department, Prof. Jan Verschuuren team. LUMC is the reference center for myasthenia gravis in the Netherlands.
piCHEM (Austria), a CMO with GMP facility expert both in peptide synthesis and conjugation, as well as in vaccine manufacturing and formulation.
Aepodia (Belgium), a CRO specialized in conducting small and medium size clinical trials.
Inserm Transfert (France), is a company with expertise in European project management.