Enabling Discovery, Development, and translation of treatments for Cognitive Dysfunctions in Depression: A Workshop Session IV

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Enabling Discovery, Development, and translation of treatments for Cognitive Dysfunctions in Depression: A Workshop Session IV Maria Isaac, MASc, MD, PhD, MFPM, Psychiatrist Senior Scientific Officer Institute of Medicine of the National Academy of Science 24-2-2015 An agency of the European Union

Disclaimer The views expressed in this presentation are the personal views of the speaker and may not be understood nor quoted as being made on behalf of or reflecting the position of EMA or one of its committees or working parties or any of the national agencies. Other positions: Vice Chair of the Psychopharmacology Special Committee of the Council of the Royal College of Psychiatrists, UK. Previous : Consultant Psychiatrist & Co-Director of Psychopharmacology Evaluation Unit at the South London & Maudsley NHS trust in London and Honorary Senior Lecturer in the Department of Forensic and Neurodevelopmental Sciences at the Institute of Psychiatry, Kings College London, UK. 1

Goals of this session: Provide an overview of the Qualification of Novel Methodologies procedure, SAWP & CHMP Establish the Regulatory framework for the Qualification Procedure Procedural aspects and definitions Parallel FDA-EMA qualification procedure Examples: EU-AIMS, MSOAC, CAMD. 2 05 March 2015

CHMP centralised evaluation Applicant (Co)Rapporteurs Assessment Report Day 80 Primary Evaluation Phase CHMP List of Questions Day 120 Stop Clock Max. 6 m Day 121 Response to LoQ Start Clock Hearing? Day 180 Stop Clock Hearing Day 181 Start Clock Secondary Evaluation Phase Day 1 Biotech MPs recombinant DNA controlled gene expression mabs Orphan MPs Day 150 Joint Rapp./ Co-rapp. AR Day 210 Adoption of Opinion (in English) Therapeutic areas Oncology Neurodegenerative disorders ATMPs Reg 1394/2007 Diabetes Autoimmune and immune disorders Viral diseases, HIV/AIDS Maria Isaac, EMA Scientific Advice Regulation (EC) No 726/2004 - Annex I

Scientific Advice Working Party standing WP of the CHMP (Reg. 726/2004) multidisciplinary expert group (28) selected by expertise (not MS) 16 NCAs, 12 academia; members of EMA committees 3 COMP, 1 CAT, 2 PDCO CHMP peer-review, ad hoc discussions, adoption final advice letter CMC: starting materials, specs, comparability, bridging non-clinical: overall toxicology plan registration, innovative models clinical pharmacology: PK/PD, modeling & simulation, BE clinical therapeutic areas: endpoints, population, comparator methodology, statistics: interim A, adaptive/seamless design network of external experts 4 4 05 March 2015

EU Guidance for Qualification of Novel Methodologies New regulatory procedure (2008, revised in 2014) Voluntary, scientific pathway for innovative methods or drug development tools (e.g. biomarkers) not yet integrated in the drug development and clinical management paradigm One procedure with two outcomes: Qualification Advice, OR Qualification Opinion Long-term benefits from EMA prespective: Speed-up the time to regulatory acceptance of novel approaches and time to new marketing authorisation applications

Qualification of Novel Methodologies Vision: Speed up/optimise drug development and utilisation, improve public health Procedure to guide the development of new more efficient ways to develop drugs, e.g. development of new endpoints for clinical trials: E.g. Can changes in chemicals (biochemistry) or structures (imaging/mri) in the brain predict the development of Alzheimer s disease before the patients lose their memory and cannot function so that a medicine can intervene early on and be more effective? Started 2008: 60 procedures so far 6

Qualification Advice vs Qualification Opinion Qualification Advice Qualification Opinion Prospective PLANS i.e.: Draft protocols and development plans for future studies to establish the use of a defined novel methodology for a specific purpose and any data available to support these plans Advice on future protocols and methods for further development towards qualification Validation DATA i.e.: Protocols, study reports and supportive data to establish the use of a defined novel methodology for a specific purpose in drug development Acceptability of a specific use of the proposed methodology Based on the evaluation of scientific rationales and preliminary data Based on the assessment of submitted data Confidential Public issued for public consultation 100 day-procedure 190 day-procedure

PARALLEL FDA-EMA Qualification ADVICE Voluntary, at request of sponsor Questions on new methodology development put to both FDA and EMA Discussions between FDA-EMA, and joint discussion with sponsor Each Agency will issue separate responses to sponsor s questions in line with usual procedures Increased dialogue between Agencies and sponsor from early stages of development Exchange views, share expertise Optimise and facilitate global development, meeting both agencies requirements 05 March 2015 8 8

EU-AIMS Work Packages Identify BMs of ASD preceding onset of clinical symptoms Validate BM of ASD in children, adolescents and adults Identify molecular-physiologic pathways of drug responses Develop clinical infrastructure extend COST and ECNP networks WP1 WP2 WP3 WP4 Develop better outcome instruments, clinical trials methodology, and regulatory framework WP5 Standards, training and dissemination Slide 9

Qualification: IMI - EU-AIMSProcedures V.1. Measures of Executive Function and Theory of Mind Deficits in ASD; EU-AIMS Consortium (IMI) (EMEA/H/SAB/044/1/QA/0000/PED) V.2. MRI and EEG in ASD; EU-AIMS Consortium (IMI) (EMEA/H/SAB/045/1/QA/0000/PED) V.3. 5HT and p-cresol Chemistry Biomarkers; EU-AIMS Consortium (IMI) (EMEA/H/SAB/046/1/QA/0000/PED) V.4. Eye Tracking in ASD; EU-AIMS Consortium (IMI) (EMEA/H/SAB/047/1/QA/0000/PED) V.5. Clinical Outcomes in ASD; EU-AIMS Consortium (IMI) (EMEA/H/SAB/048/1/QA/0000/PED)

CAMD s Mission Critical Path Institute s Coalition Against Major Diseases (CAMD) accelerates the development of therapies for Alzheimer s and Parkinson s diseases by generating the best methods and tools for evaluating drug efficacy, expediting clinical trials, and streamlining review by regulatory agencies.

Qualification of a Clinical Outcome Assessment Methodology for Multiple Sclerosis Multiple Sclerosis Outcome Assessments Consortium (MSOAC)

Links EMA guidance for companies requesting SA or PA http://www.emea.europa.eu/pdfs/human/sciadvice/426001en.pdf Qualification of novel methodologies for drug developments http://www.emea.europa.eu/pdfs/human/biomarkers/7289408en.pdf Scientific guidelines Http://www.emea.europa.eu/htms/human/humanguidelines/background.htm E-mail: maria.isaac@ema.europa.eu European Medicines Agency 30 Churchill place Canary Wharf London E14 5EU United Kingdom Tel: (44-20) 3660 7153 Fax: (44-20) 3660 70 40 13 05 March 2015