FDA Consultation: FDARA Implementation Guidance for paediatric studies of molecularly targeted oncology drugs. Amendments to Sec. 505B of the FD&C Act guidance for industry

FDA Consultation: FDARA Implementation Guidance for paediatric studies of molecularly targeted oncology drugs. Amendments to Sec. 505B of the FD&C Act guidance for industry

On December 2020, the Food and Drug Administration released a draft guidance for industry entitled “FDARA Implementation Guidance for Paediatric Studies of Molecularly Targeted Oncology Drugs”. This draft guidance addresses early planning for paediatric evaluation of certain molecularly targeted oncology drugs, including biological products, for which original new drug applications (NDAs) and biologics license applications (BLAs) are expected to be submitted to FDA on or after August 18, 2020, in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act) as amended by the FDA Reauthorization Act of 2017 (FDARA). This guidance addresses the implementation of amendments made by FDARA to the FD&C Act regarding molecularly targeted oncology drugs.

In particular, section 504 of FDARA amended section 505B of the FD&C Act to require—for original applications submitted on or after August 18, 2020—paediatric investigations of certain targeted cancer drugs with new active ingredients, based on molecular mechanism of action rather than clinical indication. Up to 50% of paediatric cancers, in fact, have been reported to harbour a potentially druggable event, i.e. a molecular abnormality which can be potentially addressed by a targeted drug already approved for use in adults.

The most important novelty introduced with the amendment is that if an original NDA or BLA is for a new active ingredient and the drug is intended for treatment of an adult cancer, reports on the molecularly targeted paediatric cancer investigation must be submitted with the marketing application.

The statute directs FDA, in consultation with the National Cancer Institute (NCI), members of the internal committee established under section 505C of the FD&C Act, and the Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee, to establish, publish, and regularly update a list of molecular targets (The Relevant Molecular Target List) considered, substantially relevant to the growth or progression of a paediatric cancer, and that may trigger the requirements for paediatric investigations under PREA (Pediatric. Molecular targets that are considered “not substantially relevant” to the growth or progression of paediatric cancers and that would warrant a waiver of paediatric study requirements under PREA constitute a second list (The Non-Relevant Molecular Target Leading to Waiver List)

Although it is possible to comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that FDA considers your suggestions before the work on the final version of the guidance begins, it is necessary to submit either online or written comments by 12 February 2020, by using the form available here.

In Europe, the European Medicines Agency (EMA) released the revised Guideline on the evaluation of anticancer medicinal products in man (last revision come into effect on April 2018) that came into effect on 1st April 2018 and aimed to provide guidance on all stages of clinical drug development for the treatment of malignancies, including drug resistance modifiers or normal tissue protective compounds. Moreover, a revised addendum on Paediatric Oncology to the above mentioned guideline has available since 1th January 2004 (new revision in progress) that should be read in conjunction with ICH E11 guideline on Clinical investigation of medicinal products in the paediatric population. Finally, the Paediatric Committee of EMA (PDCO) released an inventory of paediatric needs including medicines with mechanisms of action relevant for paediatric diseases/subgroups.

So, despite the great attention paid for the importance of challenges of the anticancer treatment development in paediatric population, in Europe the possibility to integrate and require the molecularly targeted paediatric cancer investigation for new active ingredient/drug for treatment of an adult cancer has not still foreseen by the European Competent Authority.

However, this approach could be a key strategy to overcome some challenges in paediatric drug development due to rarity of paediatric cancers.

In fact, malignancies occurring in children and adolescents can harbour the same molecular abnormalities as those found in adult cancers, and therefore, many new targeted oncology drugs may prove effective in the treatment of paediatric patients with cancer, even if the adult cancer indication does not occur in the paediatric population.

January 27th, 2020|