A) Session 3: Clinical Trials In Neonatal And Paediatric Clinical Pharmacology

3 Paediatric investigation plans in systemic lupus erythematosus: review of the PDCO’s experience

Abstract

Introduction Recently, the identification of new treatment pathways has led to the initiation of several new medicine developments in Systemic lLupus Erythematosus (SLE). However, compared to adult disease, juvenile-onset SLE (jSLE) exhibits increased disease activity, earlier tissue damage requiring more aggressive treatments. Therefore, appropriate paediatric development is needed.

Methodology The European Medicines Agency (EMA) reviewed aspects of the Paediatric Investigation Plans (PIPs) agreed by the Paediatric Committee (PDCO) at the EMA in SLE in the period since the Paediatric Regulation came into force until today (2007–2022) to identify current challenges.

Results So far, the PDCO has evaluated 30 submissions for PIPs for (j)SLE. All PIP related products are also being developed for adult-onset SLE. So far 22 have led to an agreed plan correspond to 21 different active substances, each with a different mechanism of action. 4 of them are being specifically developed to target lupus nephritis.

The agreed PIPs focus on patients from 5 years of age, and on average each PIP includes only a single clinical trial (14 of them vs 7 with 2 and one with 4 trials). Of the 32 planned clinical trials included in the PIPs, 14 are RCTs versus placebo, as add-on to standard of care.

On average, a sample size of at least 83 patients was required in the main trial and 17 PIPs contained an agreed modelling and simulation analysis to support appropriateness of paediatric dosing and/or analyse pharmacokinetics/pharmacodynamics (PK/PD).

Belimumab was the first biologic treatment that obtained a paediatric indication for (j)SLE above 5 years of age in the EU. Extrapolation of efficacy data from adults and older paediatric patients eventually allowed regulators to grant an indication in the younger age groups.

Results from other PIPs are awaited.

The number of PIPs for the treatment of (j)SLE evaluated by the PDCO highlights a very competitive area where agreed developments are relatively consistent, but recruitment of paediatric patients seems to be challenging.

Conclusions Stand-alone developments might not deliver results and answer the most pressing research questions in the required timeframe. Therefore, innovative designs considering different mechanisms of actions, potential synergistic effects, potential prioritisation should be explored. Furthermore, research should also focus on bridging biomarkers, to make better use of extrapolation of efficacy from adults.

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