PDCO current approach Medicines for Paediatric NASH overview of - - PowerPoint PPT Presentation

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pdco current approach

PDCO current approach Medicines for Paediatric NASH overview of - - PowerPoint PPT Presentation

Jan 27, 2024 911 likes •1.03k views

PDCO current approach Medicines for Paediatric NASH overview of current paediatric investigation plans Presented by Chrissi Pallidis on 3 December 2018 European Medicines Agency Paediatric Medicines Office An agency of the European

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An agency of the European Union

PDCO current approach

Medicines for Paediatric NASH – overview of current paediatric investigation plans

Presented by Chrissi Pallidis on 3 December 2018 European Medicines Agency – Paediatric Medicines Office

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Paediatric NASH

Incidence rising
No licensed pharmacotherapy
Need for effective and safe treatments
Many new medicines in the pipeline
How can we optimise development in

children?

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Paediatric NASH - differences

Histopathological differences:

Type 1 (adult pattern) – steatosis with ballooning degeneration and lobular

inflammation, with or without perisinusoidal fibrosis and without portal inflammation 17%

Type 2 – macrovesicular hepatocellular steatosis with portal inflammation, with or

without portal fibrosis in the absence of ballooning degeneration and perisunusoidal fibrosis 51% Schwimmer et al

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Agreed Paediatric I nvestigation Plans

Elafibranor
Simtuzumab
Obeticholic acid
GS-0976
Selonsertib
Cenicriviroc

3 additional procedures under discussion

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PDCO current approach

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Waivers: Mostly below 2 years, some below 8 years Quality: Development of age appropriate formulations Non-clinical: Juvenile toxicity studies in some cases

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PDCO current approach

Clinical

Double-blind, placebo-controlled
PK (either separately or as part of main study) in addition to safety and efficacy
Primary endpoint: Proportion of subjects with fibrosis improvement (≥1-stage

improvement in NASH CRN) with no worsening of NASH (defined as ≥1-point increase in hepatocellular ballooning or lobular inflammation)

Secondary endpoints: liver biomarkers, incidence of liver-related clinical outcomes,

assessment of liver fat by MRI, MR Spectroscopy, ultrasound

Study duration: 12 months but also 88 weeks, 96 weeks

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PDCO current approach

Separate studies for 2 to < 8 year olds in most PIPs Deferred and to be conducted after studies in older children

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I ssues for discussion

Age of patients in clinical studies?
Endpoints – possibility of non-invasive

methods of assessment?

Optimal duration of studies?
Extrapolation from adults?

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Thank you for your attention

[ chrissi.pallidis@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

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