OFEV (nintedanib)- In children and adolescents from 6 to 17 years old interstitial lung diseases (ILDs)

The clinical benefit of OFEV 25 mg, 100 mg and 150 mg (nintedanib) is moderate in the MA indications.

Considering:

• pharmacokinetic data demonstrating exposure values(AUCτ,ss) with the dosage regimen in children and adolescents comparable to those in adults with the dosage of 150 mg twice daily, with geometric means for the area under the curve as a function of time at steady state (AUCτ,ss) of 175 ng/mL·h and 170 ng/mL·h, respectively for children and adolescents, and 181ng/mL·h for adults. These data were obtained from a phase 3 comparative, placebo-controlled, randomised, study (InPedILD), conducted using a double-blind protocol followed by open-label treatment with nintedanib, in children and adolescents aged 6 to 17 years with clinically significant, progressive ILDs, for which the primary objective was to assess the exposure dose and safety of nintedanib compared to placebo;
• extrapolation of data from adults to children, associated with a comparable safety profile. The efficacy and safety were evaluated in adults with clinically significant, progressive ILDs in the INBUILD study. The results demonstrated that nintedanib slowed down the decline in lung function, with an adjusted mean annual rate of decline in forced vital capacity (FVC) over 52 weeks of -80.8 mL/year versus -187.8 mL/year in the placebo group, i.e. a mean difference of 107.0 ml/year (95% CI [65.4; 148.5]; p<0.001). In addition, the efficacy and safety were evaluated in adults with SSc-ILD in the SENSCIS study. The results demonstrated a statistically significant difference in favour of nintedanib compared to placebo: adjusted mean difference between the two groups of 40.95 mL/year for FVC, i.e. a mean reduction of around 43.8% in the annual decline of FVC on treatment with nintedanib compared to placebo;
• the safety profile in children marked mainly by gastrointestinal toxicity;
• the unmet medical need in this rare disease in the absence of a therapeutic alternative with an MA;

but also the following limitations:

• the absence of robust data on a relevant clinical endpoint and quality of life in a paediatric population in whom the impact of ILD is particularly high;
• the high level of heterogeneity in AUCτ,ss values and the absence of assessment of the standard deviation;
• the absence of prior definition of the AUCτ,ss reference value in adults in the protocol;
• limited extrapolation of the clinical data in adults to children linked to the clinical heterogeneity of ILD between adults and children;
• the data concerning children with SSc-ILD in this study are limited, with only 7 patients with a sclerosis associated clinically progressive, fibrosing phenotype being included in the study;
• uncertainties relative to the risks related to growth and development of dentition;

the Committee deems that OFEV (nintedanib) provides a minor clinical added value (CAV IV) in the current last-resort care pathway for the treatment of children and adolescents aged 6 years and older with:

• clinically significant, progressive fibrosing interstitial lung diseases (ILDs);
• systemic sclerosis associated interstitial lung disease (SSc-ILD).