Facilitate prioritisation: The ACCELERATE-EMA Paediatric Strategy Forums. Andy Pearson and Nicole Scobie

Transcription

1 Facilitate prioritisation: The ACCELERATE-EMA Paediatric Strategy Forums Andy Pearson and Nicole Scobie 1

2 The ACCELERATE-EMA Paediatric Strategy Forums Organising Committee ACCELERATE Gilles Vassal, Andy Pearson EMA Franca Ligas, Giovanni Lesa and Koen Norga Secretariat ACCELERATE Elena Botanina, Samira Essiaf EMA Isabel Perez 2

3 The ACCELERATE-EMA Paediatric Strategy Forums 3

4 The ACCELERATE-EMA Paediatric Strategy Forums Mechanism of action biology-driven early drug development Aggregated database of paediatric biological tumour drug targets Joint academic pharmaceutical industry pre-clinical platform to analyse the activity of new drugs (ITCC-P4) Paediatric Strategy Forums Molecular profiling of paediatric tumours at diagnosis and relapse 4

5 The ACCELERATE-EMA Paediatric Strategy Forums Novel drugs with a similar MoA can then be compared in a non-competitive space, such that precious resources are not wasted, and paediatric patients are not enrolled on sub-optimal clinical studies unlikely to benefit them. However, this process involving multiple stakeholders will involve significant challenges. Pearson AD, Herold R, Rousseau R, Copland C et al on behalf Members of Working Group 1 of the Paediatric Platform of ACCELERATE. Implementation of mechanism of action biology-driven early drug development for children with cancer. Eur J Cancer. 2016; 62:

6 The ACCELERATE-EMA Paediatric Strategy Forums To facilitate dialogue and provide an opportunity for constructive interactions between relevant stakeholders (clinicians, academics, patient representatives, pharmaceutical companies and regulators) on topics requiring open discussion in the best interests of children and adolescents with cancer 6

7 The ACCELERATE-EMA Paediatric Strategy Forums Goals Share information, in a pre-competitive setting, to inform paediatric drug development strategies and subsequent decisions Facilitate development of innovative medicines for the treatment of children with cancer and ultimately introduce these medicines into the standard-of-care for children 7

8 The ACCELERATE-EMA Paediatric Strategy Forums Biology of target Content Therapeutic needs including epidemiology, clinical features, standard therapy current needs and future therapeutic plans Europe and North America Non-clinical and clinical data on compounds 8

9 The ACCELERATE-EMA Paediatric Strategy Forums 2017 ACELERATE Conference Paediatric Strategy Forum for ALK Inhibition in Paediatric Malignancies Pilot Forum 30 & 31 January 2017 Target focused Forum Comprehensive overview of the biology and therapeutic needs of patients and clinical and pharmacological information of currently available 6 compounds Greatly increased the knowledge of participants so that future decisions will be well informed 9

10 Paediatric Strategy Forum - Mature B cell malignancies in children Disease centric Forum Current therapy for high-risk mature B cell malignancies - EFS~ 95% Acute toxicity significant, but most survivors - no or mild long term toxicity Current unmet therapeutic needs are to: i) develop innovative treatments for patients remaining incurable ii) reduce high acute toxicity of current therapy; further reduction of intensive therapy leads to reduced cure and salvage regimens are not effective Many medicines in development for B cell malignancies in adults; most malignancies in adults differ from those in children 10

11 Paediatric Strategy Forum - Mature B cell malignancies in children Challenges To identify which of the many potential new drugs has optimal probability of improving cure rates in paediatric patients with chemo-resistant disease To design and execute scientifically sound studies in very small populations with relapsed mature B cell malignancies 11

12 Paediatric Strategy Forum - Mature B cell malignancies in children 73 Participants 20 Medicinal products discussed 15 Pharmaceutical companies European and North American experts in mature B cell malignancies in children and drug development Patient representatives from Unite2Cure (Europe) and Children s Cause for Cancer Advocacy (US) Regulators from EU national competent authorities, EMA & US FDA 12

13 Paediatric Strategy Forum - Mature B cell malignancies in children Classes of medicinal products Antibody drug conjugates CAR T Cells Monoclonal antibodies T-cell Engagers Checkpoint inhibitor Cell signalling inhibitors Immunomodulatory imide drugs (IMiDs) and CELMoD Cytotoxic 13

14 Paediatric Strategy Forum - Mature B cell malignancies in children Conclusions Combined adult and paediatric trials: Except for Primary Mediastinal B cell lymphoma specific paediatric studies are needed primarily due to different biology Inclusion of adolescents (aged 12 to 17 years) in adult trials is very strongly encouraged Joint leukaemia-lymphoma clinical trials are not feasible 14

15 Paediatric Strategy Forum - Mature B cell malignancies in children Conclusions Development of new front-line therapies Current frontline therapy very successful de-escalation can only be undertaken with an effective salvage regimen Priority should be directed at developing treatment for relapse Development of therapies for relapse Very small numbers of patients - global strategy Combination approach rather than monotherapy Trials for relapsed disease must integrate correlative biology studies 15

16 Paediatric Strategy Forum - Mature B cell malignancies in children Consensus of clinicians Conclusions Antibody drug conjugates (excluding a vinca alkaloid drug) CAR-T cells (as take 4 weeks for production - not products for initial use but only for consolidation) T-cell Engagers have the greatest probability of being beneficial in relapse In view of very small numbers of patients, new additional trials of cell signalling inhibitors should not commence until the results of the ongoing SPARKLE trial known 16

17 Paediatric Strategy Forum - Mature B cell malignancies in children Conclusions 14 related Paediatric Investigation Plans (PIPs) agreed / under assessment Clinicians and pharmaceutical companies :- Proposed that PIPs be adaptable in response to new data ( PIP development Life-cycle approach) Proposed that PIPs should not include obligation for front-line trials, until there are effective salvage regimens, except for PMBL Expressed concerns about number of agreed PIPs, in view of the small number of eligible patients Benefits of conducting academic sponsored clinical trials with adaptive design of compounds from different pharmaceutical companies and different mechanism of action - designed with intent to file with early input from regulators 17

18 Paediatric Strategy Forum - Mature B cell malignancies in children Summary for participants Short summary for EMA website Published manuscript Output International working group to develop a clinical trials strategy 18

19 The ACCELERATE-EMA Paediatric Strategy Forums An evolving concept Increasing dialogue - Pharmaceutical companies, academia and regulators Increasing dialogue - EU and US European, US and other international academic clinical cooperative groups work closely together Critical role of patient representatives Third Forum - Checkpoint inhibitors used in combination - 5 & 6 September 2018 at the EMA Fourth Forum - Potential topic - Acute Myeloid Leukaemia 19

20 The patient representatives perspective 20

21 Together, we can make a difference Why is our voice important? How do we see the future of these forums? 21

22 The ACCELERATE-EMA Paediatric Strategy Forums Third Forum Checkpoint inhibitors used in combination 5 & 6 September 2018 EMA Immune environment in paediatric tumours Early results of early phase trials of checkpoint inhibitors in children Opportunities for paediatric studies of check-point inhibitors in combination Other possible approaches Advert soon and Expressions of interest 22