Orphan Drug for Acanthamoeba Keratitis (ODAK)
ODAK is a research project to develop the Orphan Drug Polihexanide (PHMB) to provide a safe and effective drug for the treatment of Acanthamoeba keratitis. This is an infectious disease caused by a free living microorganism called Acanthamoeba, present in air, soil and water. The microorganism can infect eyes and is often linked to contact lens wearing, especially when poor eye-care is a factor.
Without treatment, this debilitating eye disease causes patients to suffer severe pain, vision loss and eye enucleation. Currently, there is no approved drug to treat this infectious rare disease. To improve this situation and provide an approved drug treatment, the ODAK project has been set-up. Led by SIFI SpA, an Italian company specialising in eye care products, the project is co-funded by the European Commission FP7 programme.
The ODAK project will undertake scientific research using laboratory experiments and clinical studies with patients, to provide scientific evidence to support the development of the first approved drug targeting Acanthamoeba keratitis. In addition the project will provide information and advice to doctors and healthcare providers on how to treat patients effectively.
Our research programme is expected to identify and test new PHMB formulations to find the most effective drug therapy for treating patients. Five work packages will deliver the technical aspects of the research and development project:
WP1 Pharmaceutical Technology: WP1 will undertake research to produce new stable PHMB formulations for use in non-clinical studies. Formulation stability studies over 24-months will provide data on the stability of the shortlisted drug formulations. The product and process knowledge will then be transferred to the manufacturing site at Moorfields Pharmaceuticals
WP2 None-Clinical Studies: Laboratory based investigations, called a non-clinical phase will take place early in the project. These studies will identify the safest and most effective short-listed drug formulation(s) to be tested in clinical trials based on in vitro/vivo studies. These will include:
- Pharmacodynamics: experiments to understand the effect the drug has on the body, in particular on the diseased area targeted by the drug;
- Pharmacokinetics: studies to understand what happens to the drug once it is in the body;
- Toxicology: studies to ensure that the drug is used at safe levels for patients
WP3 Manufacturing Product: Work will be carried out to manufacture PHMB batches(s) for use in clinical trials and produce supporting stability data according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines.
WP4 Phase l / Phase lll Clinical Studies: These studies will provide information to determine pharmacokinetic, pharmacodynamic/efficacy and safety data for PHMB in a phase lll clinical trial, The safest and most effective PHMB product for treating patients with Acanthamoeba keratitis will be identified and optimised in a treatment regimen for patients. Clinical trials will be carried out involving patients:
- First a review of treatments used in the past on patients with the disease, will be carried out to identify current good practice;
- Secondly tests of new formulations of the drug PHMB using healthy volunteers will be undertaken;
- Finally clinical trials will test the effectiveness of the new treatments on patients at several clinics around Europe. We hope to demonstrate that PHMB is an effective and safe therapy.
WP5 Regulatory Affairs: Data from experimental work, Good Manufacturing Practise and clinical trials will be collated in a dossier that meets the quality standards required by the European Medicines Agency.Results from WP1-4 will be used to apply for marketing authorisation of PHMB to treat patients with Acanthamoeba keratitis.
The main results will be:
- the experimental scientific evidence on the quality, safety and efficacy of PHMB as a drug treatment for Acanthamoeba keratitis;
- to provide the evidence for a Marketing Authorisation from the European Medicine Agency allowing us to distribute and sell the drug;
- recommendations to improve the treatment and management of Acanthamoeba keratitis by clincians based on the efficacy and safety evidence.
By providing an effective treatment for a rare disease the ODAK project will support the International Rare Diseases Research Consortium goal to develop 200 new therapies by 2020.
The work will be undertaken by a collaboration of European organisations supported by international experts in this eye disease and healthcare. The Project partners are: Società Industria Farmaceutica Italiana (SIFI)- S.p.A. [Italy]; University of Rouen [France]; Research Toxicology Centre S.p.A.[Italy]; Moorfields Eye Hospital [United Kingdom]; PSR Group B.V. [Netherlands]; Ceratium Limited [United Kingdom].