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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

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

Periodic Report Summary 1 - MYASTERIX (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)

Project Context and Objectives:
MYASTERIX project aims to advance a therapeutic vaccine candidate (CV-MG01 with orphan drug status) for the autoimmune disease myasthenia gravis (MG) to human proof-of-concept studies. This will provide a more targeted therapeutic approach with fewer and less severe side effects than the existing therapeutics.

The project is divided into 6 main Work Packages, WP1 management, WP2 production, WP3 toxicity study, WP4 phase 1B clinical trial, WP5, phase 2B clinical trial, WP6 exploitation and dissemination.

In period 1, the main objectives were:
1. WP2 to produce the MG therapeutic vaccine for toxicity study in R&D quality and for human usage following Good Manufacturing Practice (GMP),
2. WP3 to perform a GLP toxicity study following the current EMA, FDA and WHO recommendations and guidelines,
3. WP4 to prepare a phase 1B clinical trial and apply for a Clinical Trial Authorisation (CTA),
4. WP6 to communicate about our work and to begin the dissemination and exploitation plan in order to maximize potential future outcome of the development program.

Project Results:
1. WP2 Production
The technology transfer has been completed. T- and B-Peptide have been synthesized and purified in GMP-grade quality and large scale for further conjugations to the carrier protein to be used for animal toxicity studies and for clinical trials. Both peptides have been subjected to real-time stability studies at the storage temperature and accelerated stability studies at higher temperatures.
The two conjugates have been produced and released in R&D-grade quality to serve as drug substance for the final fill and finish resulting in the drug product named CV-MG01 Antigen – used for the toxicity studies. The final drug product has been filled in vials.
For the phase 1 clinical study, the two conjugates have been produced in GMP-grade quality similarly to the protocol that was used for the toxicity batch. The final release of the conjugates by the Qualified Person of piCHEM is pending.
CV-MG01 Adjuvant has been produced by the contract filling organization in GMP-grade quality.
All QC released intermediates and final products have been subjected to stability studies at different temperatures and different durations

2. WP3 Toxicity study
For this work, we have referred to the new WHO guideline for vaccines and adjuvants “Guidelines on the nonclinical evaluation of vaccine adjuvants and adjuvanted vaccines” from October 2013 which was not available at the time the proposal was written.

The toxicology was performed at an AAALAC facility with the toxicology batch supplied by piCHEM. Immunogenicity tests showed that the vaccine components generated their intended pharmacological action in the animals.
No adverse events were reported during the in-life phase and no differences were reported between the control group and the groups that received the vaccine or the components in terms of systemic toxicity. After full necropsy, no general adverse findings were reported.

The conclusions of the toxicity report were also used in the Clinical Trial Application (WP4).

The WP3 has been completed during the first period of the MYASTERIX project.

3. WP4 Phase1B clinical trial
The files for the Clinical Trial Application have been submitted to the national Medical Ethical Committee (CCMO) and national competent authorities. Local preparations for the clinical trials at LUMC are ongoing. Approvals from the local ethical committee CME for a pilot trial testing for tetanus vaccine have been obtained.

4. WP6 Dissemination and exploitation
In order to raise maximum visibility for MYASTERIX from potential investors and patient communities, CuraVac participated to two contests: the BioVision Catalyser where MYASTERIX was elected by a panel of independent experts as the most innovative project in the “Immunotherapies and Vaccines” section and the European Venture Contest where CuraVac received the best presentation award from a jury of investors.
CuraVac also launched the market study.
We have regular contacts with the Dutch patients’ association via Johan Voerman, member of our IAB. Dr. Huberty is in regular contact with the New Jersey and Alabama patients’ organisations and presented the project in front of these organisations in January 2015. Thanks to Biovision event, contact was established with a French patients’ organisation.

Potential Impact:
MYASTERIX project is expected to have a major impact on MG patients. Indeed the project will evaluate the anticipated benefits of a targeted therapeutic approach for MG requiring only three injections which can bring significant and lasting improvement or even a cure to MG patients. We will compare this novel treatment to current options such as general immunosuppression, which cannot cure but only control the disease, and incomplete symptomatic relief, which can only be achieved by the frequent (every 4 hours) administration of drugs like acetylcholinesterase inhibitors. The side effects of the MG therapeutic vaccine are expected to be comparable to current prophylactic vaccines. The vaccine will therefore compare favorably to the current drugs used to treat MG, which cause numerous and severe side effects.

MYASTERIX project is also expected to have medico-economic impact on patients and society. Reviews that have evaluated the current treatment strategies for MG, their numerous and severe side effects as well as their costs (Juel et al., 2005), indicate that the total average cost of treatment including all known side effects is well above the average cost of MG medication alone. Many patients also remain significantly disabled, which reduces their quality of life and their ability to work, thus causing lost revenue not only for the patients but also for society as a whole. If our vaccine is successful we will fix the market price of CV-MG01 based on the effective QALY improvement and/or the saving on the average yearly cost of treatment of MG patients. This approach will generate considerable benefits for patients and society by replacing all the primary and secondary costs with the sole cost of the vaccine and its straightforward three-injection procedure.

List of Websites:
www.myasterix.eu

Project information

Grant agreement ID: 602420

Status

Closed project

  • Start date

    1 October 2013

  • End date

    30 September 2018

Funded under:

FP7-HEALTH

  • Overall budget:

    € 7 538 399,15

  • EU contribution

    € 5 900 720

Coordinated by:

INSERM TRANSFERT SA