Community Research and Development Information Service - CORDIS

  • European Commission
  • CORDIS
  • Projects and Results
  • Periodic Report Summary 3 - 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)

Periodic Report Summary 3 - 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 2 clinical trial, WP6 exploitation and dissemination

In period 3, the main objectives were:

1. For WP1: to file the second periodic report and organise the 4th annual meeting.
2. For WP2: to perform the stability studies on the produced batches and improve the final formulation of the clinical batch and to manufacture new batches of peptides and conjugates.
3. For WP4: to finalise the phase 1b clinical trial part A and to start the part B.
4. For WP5: to gain approvals from relevant authorities and start the phase 2/3 clinical trial at UZA and LUMC.
5. For WP6: to communicate on the intermediate results of the phase 1b at scientific conference(s) and the start of the phase 2/3 to the public and with the patient organisations. WP6 also aimed to obtain a follow-up protocol assistance at the EMA.

Project Results:
1. WP2 Production

piCHEM continued with the stability studies to enable the shelf-life extension of the product used in the clinical trial at UZA. The antigen vials have now a proven stability of three years.
A better final formulation has been developed. New non-GMP batches have been produced for non-clinical studies.

2. WP4 Phase 1b clinical trial

The main achievement of the last period is the organization and completion of the part A of the phase 1b clinical trial at UZA.

Following approval of protocol version 5 by the Belgian Competent Authority (CA) and the UZA ethical committee (EC) the study was performed at UZA hospital under the supervision of Prof Rudy Mercelis as Principal Investigator.
A total of 25 patients were enrolled and 24 completed the study Part A (3 cohorts of 8 subjects each) by September 2017. Immunogenicity (antibodies against B- and T-peptides) and safety were assessed as primary endpoints. Secondary endpoints included AChR antibody titre changes and assessment of efficacy using clinical scales and questionnaires. The Part A is completed and the Part B is ongoing.
The primary objectives (safety and immunogenicity) were reached even though the immunogenic response was found to be lower than expected (on the basis of animal data), but was, on average, higher in patients who received the high dose of the vaccine compared to those who received the low dose. The safety profile was very good. Most of the Treatment Emergent Adverse Events (TEAEs) were of mild severity, a few events were of moderate severity, and very few events were of high severity regardless of the treatment groups (low dose, high dose or placebo). The most frequent adverse reactions after the subcutaneous administration of CV-MG01 were transient local reactions. There was no statistically significant difference for any of the secondary efficacy endpoints between the groups due to the small size of the groups, heterogeneity of the patients’ profile on entering the study and very low clinical scores at baseline for some patients.
The tetanus study was completed and the results published. It showed that tetanus revaccination is safe and induces an immune response in MG patients.

3. WP5 Phase 2 clinical trial

The study CV-0003 (phase 2) was designed and the protocol, informed consent document (ICD) and associated documents developed and the clinical trial application (CTA) was submitted to Belgian and Dutch competent authorities (CA) and to the respective Ethics Committees (EC) (UZA for Belgium, LUMC for Netherlands). The study was accepted in Belgium but the CTA was withdrawn from the Netherlands by Curavac due to the absence of a decision by the LUMC Ethics Committee within the regulatory timeframe. The clinical trial could not be performed at LUMC and the recruitment did not start at UZA since the Belgian site expected to recruit approximately 10% of the patients needed to complete the study. Due to these circumstances it was concluded that it would be very difficult to complete the study within the timeframe of the current project and the project is being amended to generate additional in-vitro and in-vivo non-clinical immunogenicity and efficacy data.

4. WP6 Dissemination and exploitation

Prof. Rudy Mercelis presented the intermediate results on the first two cohorts at the New York Academy of Sciences 13th International Meeting on Myasthenia Gravis and Related Disorders in May 2017 (NYAS MG13).
CuraVac attended a follow-up protocol assistance at the EMA in June 2017.
A Pre-IND meeting with the FDA was held in July 2017.
CuraVac participated in several biotech and pharmaceutical business partnering congresses.

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 have been documented, in the phase 1b, to be comparable to current prophylactic vaccines. The vaccine will therefore compare favourably to the current drugs used to treat MG, which cause numerous and severe side effects.

MYASTERIX project is also expected to have a 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, 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. Our approach could generate considerable benefits for patients and society by replacing all the primary and secondary costs with the sole cost of the active targeted immunotherapy and its straightforward three-injection procedure, which have only mild local side effects. Ultimately, if maintenance therapy and hospitalisation costs can be replaced with the costs of CV-MG01, then everyone will win: the patients, the stakeholders and society in general.

List of Websites:
www.myasterix.eu

Related information

Reported by

INSERM - TRANSFERT SA
France

Subjects

Life Sciences
Follow us on: RSS Facebook Twitter YouTube Managed by the EU Publications Office Top