The Value of a Neonatal Consortium: A Regulators Perspective - - PowerPoint PPT Presentation

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The Value of a Neonatal Consortium: A Regulators Perspective - - PowerPoint PPT Presentation

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The Value of a Neonatal Consortium: A Regulators Perspective Applying Regulatory Science to Neonates: Launch of the I nternational Neonatal Consortium London, 18-19 May 2015 Presented by Ralph Bax on 17 May 2015 An agency of the European

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An agency of the European Union

The Value of a Neonatal Consortium: A Regulator’s Perspective

Applying Regulatory Science to Neonates: Launch of the I nternational Neonatal Consortium London, 18-19 May 2015

Presented by Ralph Bax on 17 May 2015 Paediatric Medicines, Product Development Scientific Support Department

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Disclaimer

The views expressed in this presentation are the personal views of the author(s) and may not be understood or quoted as being made on behalf of or reflecting the position

  • f the European Medicines Agency or one of its committees or working parties.

1

INC London May 2015

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Value of a Neonatal Consortium – first thoughts

  • First steps
  • Concepts
  • Oct 2014: 1st annual workshop

Roadmap for Applying Regulatory Science to Neonates (C-Path/ FDA, Silver Springs)

  • March 2015 Collaboration between Researchers and the EMA on challenges in development of

medicines for neonates

  • Complexity - Collective Intelligence
  • Competition – Co-operation  “Co-opetition”?
  •  Consortium

INC London May 2015 2

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Preterm birth rates

INC London May 2015 3

Blencowe H et al, Lancet 379: 2162–72, 2012

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INC London May 2015 4

Complexity

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EU Legislation - rem inder

INC London May 2015 5

  • PI P (Paediatric Investigation Plan) needed for the initial

authorisation of new products (and variations for on-patent products) -including only-adults indications- in the EU.

  • Studies in neonates and children need not necessarily be done

at the same time as in adults (deferrals > 80% of cases).

  • Reasons to w aive studies in children:
  • Likely to be ineffective or unsafe
  • Condition does not occur
  • No significant therapeutic benefit over existing treatments
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Neonates in Paediatric I nvestigation Plans

INC London May 2015 6

  • 1 in 4 PIPs specifically mention neonatal development
  • Inclusion of neonates increased in PIPs: from 15% to 28%

(2008) and from 24% to 32% (2011).

  • Further outcome analyses ongoing/ planned
  • Therapeutic areas
  • Non-clinical studies
  • Global Research in Paediatrics (GRIP, FP7) network: How to arrive

at the first dose for neonates.

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Paediatric Investigation Plans agreed in prioritised areas

INC London May 2015 7

Age group Brain Lung NEC Sepsis ROP NAS Neo

  • nly

Perinatal Asphyxia

  • 2-iminobiotin

Prevention of BPD

  • budenoside
  • azithromucin

./. Prevention

  • pagibaximab

Treatment

  • ranibizumab

./ . Neo incl AED/ Neonatal seizures

  • retigabine
  • lacosamide
  • carisbamate
  • brivaracetam

PAH/ PPHN

  • treprostinil
  • sildenafil
  • tadalafil
  • riociguat
  • bosentan
  • macitentan

Treatment

  • vancomycin
  • meropenem
  • eritoran
  • trombomodulin alfa
  • ceftriaxone / sulbactam
  • isavuconazonium
  • pozaconazole
  • caspofungin

NEC necrotising Enterocolitis ROP retinopathy of Prematurity AED antiepileptic drugs PAH Pulmonary arterial Hypertension PPHN Pulmonary Hyper- Tension of the Newborn NAS Neonatal Abstinence Syndrome

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Paediatric Investigation Plans agreed in other areas

INC London May 2015 8

Age group Pain Cardiovascular Nutrition Neo

  • nly
  • paracetamol (moderate,

fever, iv) Treatment of neonatal circulatory failure:

  • dobutamine

Prevention of growth retardation due to lack of bile-stimulated lipase in enteral nutrition:

  • bucelipase alfa

Neo incl

  • glucose (procedural)
  • tapentadol (acute/ chron)
  • morphine (moderate

severe/ prolonged)

  • fentanyl citrate (acute,

pre-medication) Treatment of hypotension in the extremely low gestational age newborn.

  • dopamine

Supplementation of amino-acids where parenteral nutrition is required.

  • Neoven
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Value of an INC - regulator’s point of view

  • Public Health Need– more and better, safe and effective medicines for neonates
  • Increase high quality, ethical research into medicines for children
  • Increase availability of authorised medicines for children
  • Increase inform ation on medicines
  • Without unnecessary studies in children/ delaying authorisation for adults
  • EnprEMA, Support funding initiatives, Paediatric Inventory
  • INC
  • Additional platform/ channel for communication and proactive work
  • Most efficient use of regulatory tools (e.g. PIP, SA, qualification of novel

methodologies)

  • Learning from other stakeholders

INC London May 2015 9

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Acknowledgement

Paediatric team EMA Isabel Perez, Ralf Herold, Roberto DeLisa, Andrea Ecker, Irmgard Eichler, Giovanni Lesa, Thorsten Olski, Cecile Ollivier, Chrissi Pallidis, Dobromir Penkov, Paolo Tomasi

INC London May 2015 10

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Thank you for your attention

paediatrics@ema.europa.eu

European Medicines Agency

30 Churchill Place • Canary Wharf • London E14 5EU • United Kingdom

Telephone + 44 (0)20 3660 6000 Facsim ile + 44 (0)20 3660 5555 Send a question via our w ebsite www.ema.europa.eu/ contact

Further information

Follow us on @EMA_ New s

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EnprEM rEMA

  • En

Enpr-EM EMA = European ean Netw twork of

  • f Paed

aediatr tric Res esear earch ch at at th the European ean Med edicines es Agency cy

http tp://www www.em ema.eur urop

  • pa.eu/ema/

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nt_000 000303 303.jsp&mid id=WC WC0b01 01ac ac0580 05801df df74 74a

  • En

Enpr-EM EMA is is a ne networ

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esear earch ch network rks, s, inve vest stigators rs an and cen centr tres es with th exper erti tise in in perf rform rming clin linic ical stu tudies es in in th the paed aediatr tric po popu pulation with th th the mis issio ion of

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acilita tati ting dr drug tria ials ls in in order er to to incr creas ease th the av avai ailab ability ty of

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  • n .
  • Workin

ing group up 4: Dialog

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ue an and Inter teracti tion with th Et Ethic Committ ttees ees

12

Slide B. Pelle, EMA-EnprEMA

INC London May 2015

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Breakdo kdown wn o

  • f netwo

works rks b by t type pe a and catego gory y

13

National Oncology/ Haem atologic Malignancies Diabetes/ Endocrinology/ m etabolic disorders/ Gynaecology Gastroenterology/ Hepatology Allergology/ I m m unology/ Rheum atology Stem Cell / Organ Transplantation/ Haem atology/ Haem os taseology Respiratory diseases / Cystic Fibrosis

NI HR-MCRN New clastle-CLLG ESPGHAN PRI NTO EBMT ECFS-CTN ScotCRN EPOC PEDDCReN FinPedMed I TCC JSW G of PRES I PTA MCRN-NL I BFMSG MI CYRN CLG- of EORTC CI CPed

Category 1 : Networks fulfilling all minimum criteria. Category 2 : Networks potentially fulfilling all minimum criteria – but needing to clarify some issues. Category 3 : Networks currently not yet fulfilling minimum criteria. Category 4 : Networks not performing clinical trials; e.g. methodology, infrastructure, etc.

I PCRN NCCHD BLF RI PPS Futurenest CR Sw issPedNet Red SAMI D NCCHD-Japan

SPECI AL ACTI VI TI ES / AGE GROUPS Unable to fill self-assessm ent report

Cardiovascular diseases/ Nephrology Psychiatry/ Neurology I nfectious diseases/ Vaccinology I ntensive Care/ Pain/ Anaesthesiology/ Su rgery European neonatal netw ork European paediatric pharm acists special activities (Phv, long term follow up, community paediatricians) Expertise in clinical trial m ethodology

EUNETHYDI S PENTA-I D Pediatric Critical Care GNN FI MP-MCRN TEDDY UKPVG EuroNeoNet PRI OMEDCHI LD Neo-circulation ECRI N I NN GRI P ESDPPP

INC London May 2015

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INC London May 2015 14

Need for clinical trials in neonates Vulnerable population, often treated with multiple medicines at the same time (up to 60) Just like children are not small adults, neonates are not small children, therefore extrapolation of efficacy or safety from older children is very often inappropriate Neonates are the paediatric population for which less data are available on the correct use of medicines Gradual maturation of metabolic and detoxifying pathways during the first months of life cause different sensitivity and response to active substances and excipients

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INC London May 2015 15

Ethical and scientific argum ents in favour of protecting children through clinical trials, not from them Higher incidence and severity of adverse drug reactions in “off-label” use of medicinal products Efficacy cannot be assumed when prescribing medicines not tested in the appropriate population Inclusion of a child in a clinical trial is likely to be associated with a better outcome than “off- label” use Failure to conduct clinical trials in children is unethical as it forces physicians to do uncontrolled experiments almost every time they prescribe a medicine to a child