Overview of one-year experience of PRIME eligibility assessment - PowerPoint PPT Presentation

Overview of one-year experience of PRIME eligibility assessment First anniversary of PRIME: experience so far, 19 May 2017 Presented by Robert Hemmings SAWP chair An agency of the European Union

Eligibility to PRIME scheme Based on Accelerated Assessment criteria No satisfactory method or if Medicinal products of major method exists, bring a major public health interest and in therapeutic advantage particular from the viewpoint of therapeutic innovation. Introducing new methods or improving existing ones  Potential to address to a significant extent an unmet medical need Meaningful improvement of  Scientific justification, based on data and efficacy (impact on onset, evidence available from nonclinical and duration, improving morbidity, clinical development mortality) 1

One year of PRIME 108 requests received > 90 eligibility requests assessed > 50% from SMEs 20 granted* + Publication of report and list of products on EMA website 22% success rate 2

PRIME over time 9 requests per month on average Good quality of (range: 4-18) applications Few ‘out of scope’ applications Academic or SME with • no FIM data Non-SME with no • exploratory data Issue with definition as • medicinal product Resubmission with no • new data 3

Requests covering wide range of therapeutic areas and product type 70 % in oncology/haematology 34% of requests for ATMPs 4

Assessment of eligibility requests: 40-day procedure Final recommendation Policy issues EMA & SAWP Oversight CAT* SAWP CHMP reviewers group appointed sponsor Short, lean process, involving multiple committees for robust assessment 5 *For advanced therapies

Examples of Oversight group policy discussions Products in late stage of development 6

Examples of Oversight group policy discussions Products in late Main focus of PRIME is to stage of support early in development development Before denying, consider additional benefits of PRIME for the concerned development and type of product 7

Examples of Oversight group policy discussions Products in late stage of development Comparison to products under development or evaluation 8

Examples of Oversight group policy discussions Products in late stage of Other products under development development or evaluation do not yet fulfil the unmet Comparison to medical need products under development or evaluation 9

Examples of Oversight group policy discussions Products in late stage of development Unmet medical need Comparison to products under development or evaluation 10

Examples of Oversight group policy discussions Products in late Can be agreed: stage of in subgroup , if clearly defined, development with mechanistic rationale for use vs entire population Unmet medical Comparison to need in prevention setting and products under prevention of clinical complication if development or relevance duly justified. evaluation in non-life threatening condition 11

Examples of Oversight group policy discussions Products in late Requests based on stage of literature development Unmet medical need Comparison to products under development or evaluation 12

Examples of Oversight group policy discussions More acceptable at proof of principle Products in late Requests based on stage of Use of literature may not be literature development applicable similarly between Unmet medical chemicals, biologicals and ATMPs need Comparison to Need reliable, trustworthy, high products under quality literature development or evaluation Applicant planning further studies 13

Examples of Oversight group policy discussions Products in late Requests based on stage of literature development Unmet medical need Comparison to Extrapolation of products under data from other development or products evaluation 14

Examples of Oversight group policy discussions Products in late Expect data generated with the Requests based on stage of product itself literature development Unmet medical Acknowledge possibility for other need Comparison to products’ data to be supportive Extrapolation of products under (e.g. in cases with surrogate data from other development or marker validated) products evaluation 15

Entry points of PRIME eligibility requests Nonclinical Phase I Exploratory Confirmatory Confirmation Any SMEs sponsor Academia Proof of principle Proof of concept (For SMEs and academia only)  Sound pharmacological rationale  Sound pharmacological rationale, convincing scientific  Clinical response efficacy and concept safety data in patients (exploratory trials)  Relevant nonclinical effects of sufficiently large magnitude and  Substantial improvement duration  Magnitude, duration, relevance  Tolerability in first in man trials of outcomes to be judged on a case by case basis 16

Entry points of PRIME eligibility requests Nonclinical Phase I Exploratory Confirmatory Confirmation Any SMEs sponsor Academia Proof of principle Proof of concept (For SMEs and academia only)  Sound pharmacological rationale 86  Sound pharmacological 5 rationale, convincing scientific  Clinical response efficacy and concept safety data in patients (exploratory trials)  Relevant nonclinical effects of sufficiently large magnitude and  Substantial improvement duration  Magnitude, duration, relevance  Tolerability in first in man trials of outcomes to be judged on a case by case basis 17

Proof of concept: phase of supportive studies Mostly data from phase 1-2 > 50% with supportive data from only 1 study 18

Proof of concept: study data and number of patients Data from randomised and controlled trial Number of patients in target population No correlation between study type, number of patients and success rate 19

Proof of principle ‘early’ stage: only 1/5 request granted Main reasons for denial Weak pharmacological rationale, insufficient nonclinical evidence on the claimed mechanism of action Limited relevance of animal models presented Insufficient PK exposure data to support expected clinical outcome 20

Reasons for denial at proof of concept stage Late Insufficient stage effect size (14, 21%) (26, 39%) Issues with robustness Failures of similar developments (47, 70%) (4, 6%) Unmet medical need not sufficiently justified (3, 4%) Other reason (3, 4%) N=67 requests denied 21

Reasons for denial at proof of concept stage: Examples of robustness issues Trial design issues eg treatment effect not isolated from other factors, use of concomitant treatments Failed study Inconsistency of results across studies, study groups or endpoints Claim in subgroup insufficiently justified Sample issues size, heterogeneity, insufficient information on baseline Comparison to inadequate historical control data 22

What do we expect to grant eligibility? Unmet medical need No treatment, or clear limitations of existing therapies (e.g. Alzheimer’s disease) Nonclinical data supporting pharmacological rationale (e.g. gene therapy) Clinical exploratory data on relevant endpoint If uncontrolled, use comparable historical control i.e. need sufficient information on baseline characteristics Magnitude of the effect size supporting major therapeutic advantage 23

5 re-submissions following denied eligibility 1 If unclear outcome, applicants can Out of scope no new data contact EMA for further clarification Different reviewers appointed to 3 resubmission Limited new data/information Important to bring new evidence Denied and not just re-discussion 1 If new data, should not be too New data late in development 24

In summary, Eligibility review: robust, short time, in writing Quality of applications received is generally high Substantiate the reliability of comparisons to external control Proof of concept data and policy considerations determine timing for eligibility request Resubmission should include new elements

Thank you for your attention Further information prime@ema.europa.eu European Medicines Agency 30 Churchill Place • Canary Wharf • London E14 5EU • United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact Follow us on @EMA_News #PRIME