Life Science Leadership Series: Strategies and Funding of Clinical Trials

Transcription

1 Life Science Leadership Series: Strategies and Funding of Clinical Trials UK Early Access to Medicines Scheme Dr Daniel O Connor Expert Medical Assessor

2 Disclaimer The views expressed do not necessarily reflect the official position of the MHRA

3 Earlier access to medicines A key challenge confronting regulators and other stakeholders is earlier patient access to innovative medicines, particularly in areas of unmet medical need Ultimately there is often a fine balance between denying patients potentially useful drugs and approving products for which the drug development is considered as immature However, it is recognised that with greater medical needs e.g. life threatening conditions with no adequate treatments, it is acceptable to make decisions based on a greater degree of uncertainty in the data Evidence versus access balance

4 Earlier access to medicines In 2014, two regulatory initiatives were launched to try and address some of the pressing patient access issues: A European initiative, adaptive licensing, an emerging concept of staggered marketing authorisation approval, using existing regulatory tools» This more systems approach involving more stakeholders, is now called Adaptive Pathways A UK initiative, Early Access to Medicines Scheme (EAMS), which aims to give access to medicines that do not yet have a marketing authorisation but meet an unmet medical need

5 UK Early Access to Medicines Scheme

6 EAMS Milestones Ministerial Industry Strategy Group The Prime Minister s Strategy for UK Life Sciences Early Access to Medicines Scheme Consultation Expert group on the innovation in the regulation of healthcare Early Access to Medicines Scheme launch Step I: the Promising Innovative Medicine (PIM) Designation Step II: the EAMS Scientific Opinion Summary and update

7 Ministerial Industry Strategy Group (MISG) The MISG brings together government and the research-based pharmaceutical industry to promote a strong and profitable UK-based pharmaceutical industry In 2008, a proposal for an EAMS was developed as part of a series of events established by the MISG The Regulatory Working Group forum considered there was support from all stakeholders that earlier access to medicines could bring benefits to patients The Working Group developed an early framework for the EAMS Acknowledging that whilst access to such medicines will at least in most cases be at the end of the formal development stage, the scheme could still provide potentially life-saving treatments around one year earlier than at present

8 Strategy for UK Life Sciences EAMS Public Consultation In December 2011 the Prime Minister announced a new Strategy for UK Life Sciences The publication detailed actions aimed at maintaining the UK s world-class reputation in life sciences, improving patient health and acting as a catalyst for economic growth One of these commitments was that the MHRA will bring forward for consultation proposals for a new Early Access Scheme The Strategy set out the guiding principles for the scheme as: eligible products will be determined by a scientific opinion that the likely clinical benefits outweigh the risks identified to date where there is high unmet need; NHS funding for product must be cost effective; the UK economy should benefit from the scheme

9 Strategy for UK Life Sciences EAMS Public Consultation The MHRA and Department Health launched a joint public consultation from 13 July to 5 October 2012 There were 26 questions in the following areas: Should a scheme be established Scope Number of products Stage of development Patient treatment if medicine fails to be granted a licence Information requirements Monitoring and surveillance Questions on funding Macroeconomic gains to the UK Fees

10 EAMS Consultation Responses 52 responses were received and the Government s response to the consultation was published in March 2014 Overall, there was overwhelming support for a scheme The Government, in considering EAMS, stated that: EAMS addresses a public health need to improve access to important innovative medicines for patients with life threatening or seriously debilitating conditions without adequate treatment options EAMS demonstrates a commitment from the UK to pharmaceutical innovation, through the Promising Innovative Medicine designation and earlier patient uptake of new innovative medicines in the health service

11 Strategy for UK Life Sciences UK Expert Group The creation of the Expert Group on innovation in the regulation of healthcare was also in the Strategy and was established in June 2012: A group of experts drawn from government, regulators, the NHS, industry and the academic and third sector communities will meet quarterly to discuss healthcare regulation issues, including the development of new initiatives and innovations The group considered maximising the impact of, and learning from, the Early Access Scheme consultation The Expert Group published a report in September 2013 In the report, the group welcomed the proposal for a UK EAMS and endorsed the draft Government response to the consultation The group advised that the scheme should be launched as soon as cross- Government agreement was obtained

12 Strategy for UK Life Sciences UK Expert Group The expert group also considered the regulatory flexibilities available in the USA and EU and noted that the two regulatory licensing systems offered substantively similar flexibilities However, one difference was the FDA s breakthrough designation The Expert Group recommended that the Government consider the possibility of adopting a UK designation step, perhaps in the context of the proposed UK Early Access scheme As a result of this recommendation, the MHRA introduced the Promising Innovative Medicines (PIM) designation - step I of EAMS

13 Early Access to Medicines Scheme launch

14 EAMS A month after the responses were published, the MHRA launched the scheme (April 2014) Dedicated MHRA webpage with detailed guidance and application forms/ templates EAMS coordinator to ensure swift and efficient operation of the scheme: eams@mhra.gsi.gov.uk

15 Early Access to Medicines The scheme will cover medicines that are not yet available as licensed treatments The scheme is not a substitute for appropriate clinical development and inclusion of patients in well designed clinical studies remains the preferred option, if available in the UK Primarily aimed at medicines that have completed Phase III trials, but may be applied to completed Phase II trials in exceptional circumstances There is no set limit on the numbers of products entering the scheme provide they fulfil the criteria of the scheme The UK scheme will operate within the current regulatory structure and is voluntary The medicine is to be provided for free by the company during the scheme

16 The EAMS criteria The criteria of suitability for an EAMS application are: Life threatening or seriously debilitating conditions, without adequate treatment options high unmet need. This could include drugs intended for the treatment, prevention or diagnosis of diseases The medicinal product offers promise - that it is likely to offer benefit or significant advantage over and above existing treatment options Potential adverse effects likely to be outweighed by benefit. i.e. the benefit: risk ratio is concluded as being positive The Applicant is able and willing to supply the product and to manufacture it to a consistent quality standard (GMP)

17 EAMS - Step I & Step II The EAMS is a two step process: Step I the Promising Innovation Medicine (PIM) Designation Step II the EAMS Scientific Opinion A PIM Designation is an early indication that a medicinal product is a promising candidate for the EAMS The PIM will be issued after an MHRA scientific designation meeting on the basis of non-clinical and clinical data available on the product, in a defined disease area A PIM designation is a prerequisite to enter the EAMS scientific opinion assessment (step II)

18 Step I PIM Designation The PIM destination gives: A company reassurance that its clinical development is on track by having an early review of its data by the UK medicines regulator An opportunity to engage with NICE (HTA) and the NHS (National Health Service) on patient access issues

19 Step I Step II PIM designation awarded on the basis of Phase I/II data Early Access to Medicines presubmission meeting Enter Scientific review for EAMS opinion PIM designation awarded on the basis of Phase II data Early Access to Medicines presubmission meeting Enter Scientific Scientific review review for for EAMS EAMS opinion opinion Joint PIM designation and Early Access to Medicines pre-submission meeting, on the basis of Phase III data (exceptionally Phase II) Enter Scientific review for EAMS opinion

20 PIM - How to apply Applicants seeking a PIM designation should consult the available guidance and complete the PIM designation template in full, indicating how the product fulfills the criteria for designation The Application template includes: Administrative and product specific information Brief details of current pharmaceutical development Criteria 1: Details of the condition and details of the high unmet need Criteria 2: The medicinal product is likely to offer major advantage over methods currently used in the UK Criteria 3: The potential adverse effects of the medicinal product are likely to be outweighed by the benefits, allowing for the reasonable expectation of a positive benefit/risk balance For a joint PIM designation/ pre-submission meeting, both a PIM designation application template and a pre-submission meeting template should be submitted at the time of the request

21 Post PIM Designation Following designation, the applicant is expected to complete a clinical development programme within a reasonable time period, in order to continue with an application for an EAMS scientific opinion Designation holders are strongly encourage to utilise the MHRA s support services including: The MHRA Innovation Office that helps organisations navigate the regulatory framework Scientific advice meetings Designation holders are also strongly encourage to seek joint scientific advice meetings between the MHRA & NICE, and engage early with the NHS on patient access issues

22 Step II Scientific Opinion The scientific opinion will describe the benefits and risks of the medicine and will support the prescriber and patient to make a decision on using the medicine before its licence is approved To enter step II, the Applicant must hold a PIM designation, complete the pre-submission template and attend (either in person or via teleconference) a pre-submission meeting The aim of the pre-submission meeting is to ensure that the suitability criteria for the scheme are likely to be met and to discuss the format of the data to be submitted to support the benefit/risk opinion After the pre-submission meeting, the MHRA will make a recommendation as to whether the product is considered a suitable candidate for step II of the EAMS However, it is ultimately the decision of the Applicant whether to proceed

23 Entry into Step II Data format requirements are in line with established regulatory guidance (CTD) and/ or option to submit non-ctd data The EAMS dossier should be submitted in electronic format by the date specified and agreed after the pre-submission meeting Late or invalid dossiers will not be able to enter the scheme on the preferred date as the timetables are set to coincide with our expert committee meetings The assessment timetable is fast and flexible Lengthen clock stops if required Close before Day 75 if all issues are resolved

24 Day 75 Timetable Day 90 Timetable Days 0-45 MHRA assessment & consultation with CHM/EAG, list of outstanding issues communicated to Applicant, with provisional Benefit: Risk (B:R) opinion Preliminary positive opinion (Minor issues outstanding) Applicant requests revert to Day 90 procedure Preliminary negative opinion (Major issues outstanding) 15 day clock stop 30 day clock stop* Days 46-75: Final B:R decision positive on or before Day 75 Days 46-75: Preliminary B:R decision now negative MHRA considers Day 90 procedure required Days 46-90: Final B:R decision made on or before Day 90 positive or negative opinion *in exceptional circumstances, the Applicant can request additional 30 days (30+30)

25 EAMS Scientific Opinion A scientific opinion is only issued if the criteria for the EAMS are considered to be fulfilled and the benefit risk is positive The details of the opinion will be made available on the MHRA s website to assist clinicians and patients in making treatment decisions: A public assessment report (PAR) Treatment protocol for patients Treatment protocol for healthcare professionals Treatment protocol on the pharmacovigilance system The opinion will be valid for one year, renewable if necessary and appropriate

26 Periodic Update During the opinion year, it is expected that the scientific opinion holder will provide regular updates The frequency and scope of these updates will be agreed before the issue of a positive scientific opinion Updates are likely be expected every 3 months, describing safety and usage of the product under the scheme, along with any safety and efficacy data from newly-completed clinical trials MHRA will amend the PAR and treatment protocol as necessary, in light of emerging information Where relevant, quality, safety and efficacy data generated during the EAMS opinion should be submitted at appropriate time points during the marketing authorisation application

27 EAMS Scientific Opinion First scientific opinion was given in March 2015 for Pembrolizumab for the treatment of advanced melanoma Current EAMS SO are published in the format opposite Expired opinions are also listed on the EAMS webpage and includes the PAR and milestone dates

28 EAMS Scientific Opinions Medicinal product Indication Date of opinion Pembrolizumab (Merck Sharp & Dohme Limited) Pembrolizumab is used to treat advanced melanoma (a type of skin cancer affecting cells called melanocytes), which has spread or cannot be removed by surgery and has progressed after other treatments 9 March 2015 Nivolumab (Bristol-Myers Squibb) Nivolumab (Bristol-Myers Squibb ) Sacubitril/valsartan (Novartis) Nivolumab is indicated for the treatment of locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) after prior chemotherapy in adults. Nivolumab is used to treat advanced melanoma (a type of skin cancer affecting cells called melanocytes), which has spread or cannot be removed by surgery Sacubitril/valsartan is indicated to reduce the risk of cardiovascular mortality and morbidity in adult patients with symptomatic heart failure and reduced ejection fraction 19 June May September 2015

29 EAMS Applications EAMS step I PIM designations - April 2014 to March 2015 Applications received 10 PIM designations granted 6 PIM designations refused 1 PIM designations pending 3 EAMS step II applications - April 2014 to March 2015 Applications received 4 Opinions awarded 1 Opinions pending 3

30 Office for Life Sciences (OLS) led EAMS task force A Government-Industry Stakeholder Task Group has been established to bring together key stakeholders from the bio-pharmaceutical industry, government and arms length bodies to: Inform the development of EAMS procedures Establish consistent lines of communication between stakeholders To clarify, address and accelerate the resolution of emerging issues since launch Membership of the group includes: MHRA, NICE, NHS England, OLS, Department of Health, Devolved Administrations, Scottish Medicines Consortium, All Wales Therapeutics and Toxicology Centre, ABPI, BIA, EMIG, Invited representative companies, other stakeholders including the Centre for the Advancement of Sustainable Medical Innovation (CASMI)

31 OLS led EAMS task force The stakeholder group has produced and agreed supporting material to help explain the scheme: An agreed EAMS principles document (across the UK) An operational guidance and a schematic showing the relationships between MHRA, NICE, NHSE and the company The operational guidance will have devolved administration annexes The guidance will be updated in the light of experience and future developments e.g. Accelerated Access Review.

32 Accelerated Access Review The UK Government s Accelerated Access Review (AAR) aims to speed up access to innovative drugs, devices and diagnostics for NHS patients: Launched March 2015 Evidence gathering July-October Publish final report December 2015 The review will make recommendations to government on reforms to accelerate access The recommendations could include the role of statutory bodies including NICE and MHRA The review s ambition is to develop a joined-up, globally competitive landscape across the whole of the UK

33 Accelerated Access Review 3 key areas of potential reform Regulation: how we could more quickly assess the safety and efficacy of innovations Reimbursement: how we might adapt our systems of health economic assessment to: reflect technological advances Uptake how the NHS can better support and drive medical innovation EAMS is included as part of the review: consider how we might strengthen the Early Access to Medicines Scheme, taking into account how this fits with the Adaptive Pathways Pilot, NICE Technology Appraisal, the NICE Implementation Collaborative and other schemes such as Evaluation through Commissioning

34 EAMS Summary Aim to give patients access to medicines that do not yet have a marketing authorisation when there is a clear unmet medical need The MHRA is responsible for the scientific aspects of the scheme and the scientific opinion will be provided after a two-step evaluation process: PIM designation 8 awarded EAMS SO 4 awarded The PIM destination gives a company reassurance that its clinical development is on track by having an early review of its data by the medicines regulator Patients will be able to access important medicines before they are licensed and prescribers will have greater confidence in the safety and efficacy of prescribing The EAMS process gives the company an opportunity to engage with NICE and the NHS on patient access issues and collect real world data in the NHS

35 Thank You

36 Crown copyright 2013 About copyright All material created by the Medicines and Healthcare Products Regulatory Agency, including materials featured within these Medicines and Healthcare Products Regulatory Agency presentation notes and delegate pack, is subject to Crown copyright protection. We control the copyright to our work (which includes all information, database rights, logos and visual images), under a delegation of authority from the Controller of Her Majesty s Stationery Office (HMSO). The Medicines and Healthcare Products Regulatory Agency authorises you to make one free copy, by downloading to printer or to electronic, magnetic or optical storage media, of these presentations for the purposes of private research, study and reference. Any other copy or use of Crown copyright materials featured on this site, in any form or medium is subject to the prior approval of the Medicines and Healthcare Products Regulatory Agency. Further information, including an application form for requests to reproduce our material can be found at Material from other organisations The permission to reproduce Crown copyright protected material does not extend to any material in this pack which is subject to a separate licence or is the copyright of a third party. Authorisation to reproduce such material must be obtained from the copyright holders concerned.