HTAs and EMA working together: 23 parallel scientific advice procedures later - what have we learned? DIA 26th Annual EuroMeeting, Vienna 2014 Jan Regnstrom, MD, PhD Senior Scientific Officer An agency of the European Union
Disclaimer The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. ( DIA ), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated. These PowerPoint slides are copyright of the European Medicines Agency. Reproduction is permitted provided the source is acknowledged. 2
Overview Scientific advice from EMA Parallel scientific advice from EMA and HTAs Experience so far (2010-14) Continuity and Development 3
Scientific advice from EMA Advising Applicants on the scientific requirements for marketing authorisation (MA): Before first MA: companies ask questions on manufacturing, non-clinical and clinical trials, risk-management plans, ways to develop generics and biosimilars; significant benefit for orphan medicines; development in children. Post-MA: extension of indication to different age groups and stages of the disease; different conditions; & safety aspects. 4
EMA Scientific advice 2001-2013 5
EMA Scientific advice network SAWP - Multidisciplinary expert group External experts /Clinicians CHMP, WPs and other Committees Patient organisations HTAs 6
Scientific advice procedure Voluntary Pre-submission meetings at EMA with possibility to also discuss regulatory questions with the regulatory affairs team, ~200 meetings per year. Responses to the scientific questions are prepared and discussed by the SAWP In ~50% of the cases, in particular when the experts do not agree with the Applicant s proposal, a face-to-face Discussion Meeting with the Applicant is organised. Final written responses are discussed and adopted by the CHMP and sent to the Applicant: scientific advice letter. 7
Scientific advice advantages Unified opinion applicable across EU with regard to MAA data on medicinal products Impact on success of MAA Vast array of scientific questions Network of Experts Reasonable timeframe 40 or 70 days Voluntary SME and Orphans fees / regulatory assistance Flexibility 8
Scientific advice impact More than 70% of the Marketing Authorisation Applications coming to the Agency have received SA during the development. Obtaining and complying with Scientific Advice is strongly associated with a positive outcome of a Marketing Authorisation application: almost 90% of those who obtain and follow SA receive a positive opinion compared to 40% for those who do not follow SA. 9
Positive impact of SA adherence on MAA outcome 10
Parallel HTA-EMA why? New medicines do not reach all patients in need Regulators and HTAs answer different questions (B/R vs. added value) have different requirements in terms of evidence Aims - bring all stakeholders together early to: Optimise development plans accommodate needs of both HTAs and regulators in a common development track Improve access for patients 11
Parallel HTA-EMA experience 30 procedures, 23 finalised: Diabetes, Heart Failure Alzheimer s, Depression Oncology: lung, breast, melanoma, pancreas, leukaemia, cachexia Asthma, COPD, Rheumatoid Arthritis, Osteoporosis Multi-resistant Infections, Food Allergies, 2 Gastroenterology conditions Orphan conditions; Cell therapy; Ophthalmology Majority new mechanisms of action in respective area, new monoclonal antibodies, new chemicals, tumour vaccines 12
Parallel HTA-EMA experience Common discussions: elements necessary for the B/R assessment (regulators) and added value (HTAs) Comparator: placebo, active comparator Clinical endpoints: Survival, quality of life Duration of the trial (controlled and uncontrolled) Patient population to be included pre/postmarketing Questions for HTAs only: Cost-effectiveness model Impact on the caregiver Modelling disease natural course 13
Parallel EMA-HTA procedure HTAs variously UK, Sweden, France, Italy, Netherlands, Spain, Germany, Belgium, Austria Mostly big companies, 2 SMEs. Pre- Notification Pre- Validation Meeting Outcome Outcome: SA letter with the responses from the CHMP Minutes circulated by Applicant for individual written HTA agreement on the views expressed during the meeting 14
Parallel HTA-EMA advantages Uses experienced administration/machinery of EMA SA EMA/HTAs equal partners in a multi-stakeholder procedure Maintain respective roles and responsibilities Flexible in choice of HTAs - EMA can facilitate contacts Common Briefing document present concise but comprehensive data value proposition for HTAs Closed session between EMA and HTAs before the face to face meeting to review respective positions and identify critical divergences 15
Parallel HTA-EMA advantages 4 hour face-to-face meeting open discussion with expression of personal opinions. External experts have been shared Interaction between HTA and regulators; listening to each others views, improves understanding Allows contemporaneous evolution of your development to satisfy all parties before development plans and HTA/EMA decisions have been finalised 16
Parallel HTA-EMA examples Novel Therapy for COPD Company proposed a licensed comparator EMA agreed with licensed comparator HTA wanted to compare the value of new therapy to what it will replace, even if comparator is not licensed for use Solution: Introduction of new arm to pivotal study to include both options 17
Parallel HTA-EMA examples 2nd line treatment for a rare cancer No product authorised Company proposes placebo as control EMA agrees One HTA body requested a particular active comparator used in their country albeit not authorised 2nd HTA body requested placebo, they cannot accept by law a non authorised comparator Solution: Comparator Investigator s best choice 18
Parallel HTA-EMA when? Very early (non-clinical POC stage) Present general study design Benefit from the multi-stakeholders views on what would be needed to demonstrate benefit/risk and added value High level responses Later (prior to phase III) Precise responses regarding endpoints, comparators etc. Precise idea on how much is required and what is feasible Pharmacoeconomic questions 19
Parallel HTA-EMA max benefit Early informal contact with EMA if thinking about this Engage HTAs, scheduling critical Come early in development when things can be changed Briefing document: present concise but comprehensive data, value proposition for HTAs Constant dialogue with project manager - logistic/support Approach discussion meeting in open manner - engage 20
HTA-EMA activities Optimising procedures - EMA-HTA group works on procedure to be published for consultation. Include post-authorisation safety/efficacy studies Workshop (Nov 2013) over 300 participants: HTAs, regulators, industry, SMEs, academia, health care professionals, patient representatives, EC. EMA participation in SEED Consortium (Shaping European Early Dialogues), led by Haute Autorité de Santé (HAS): 14 HTAs, 7 MP procedures planned 2014. EMA associated with HTA Network (HTAN) of EC. 21
For more information I am available at the EMA booth to answer questions on [Wed 26/3, 16h00-17h30 and Thur 27/3, 11h00-12h30] Please visit us in the exhibition hall booth number x.605 Contact me at (Jan.Regnstrom@ema.europa.eu) Further information at www.ema.europa.eu 22