If you are planning to submit a New Drug Application (NDA) for an oncology drug product in 2020, revised pediatric study plan requirements could have an impact on the submission. FDA recently released draft guidance on changes to pediatric study requirements put in place by Section 504 of FDARA: FDARA Implementation Guidance for Pediatric Studies of Molecularly Targeted Oncology Drugs: Amendments to Sec. 505B of the FD&C Act (OCE, CDER, CBER; December 2019).

What does this change mean for Sponsors?

At first glance, it could appear that the changes are closing a “loophole” in the requirements laid out by the Pediatric Research Equity Act (PREA). Under the original requirements of PREA, many (perhaps most) new oncological products received an initial Pediatric Study Plan (iPSP) waiver from the PREA requirements to conduct pediatric studies. Waivers were granted because the adult cancer indications sought for the products occurred in small numbers in pediatric patients.

With the passage of the FDA Reauthorization Act (FDARA), many products that would have previously qualified for a waiver must now fulfill PREA requirements:

Section 505B of the FD&C Act, as amended by FDARA, requires that any original NDA or BLA submitted on or after August 18, 2020, for a new active ingredient, must contain reports of molecularly targeted pediatric cancer investigations described in section 505B(a)(3) of the FD&C Act, unless a deferral or waiver of that requirement is granted, if the drug that is the subject of the application is: (1) intended for the treatment of an adult cancer, and (2) directed at a molecular target that the Secretary determines to be substantially relevant to the growth or progression of a pediatric cancer. (Guidance at 88)

Determining if your program is impacted

As FDA explains in the guidance, the requirements reflect a shift in the scientific and medical factors used to determine which proposed oncological products will require pediatric studies. The shift is from the indication designated for the NDA product, to whether the proposed product has a molecular mechanism of action that could prove effective against pediatric cancer. Thus, the “molecular target” of the product becomes pivotal in determining where pediatric studies will be required.

FDA’s operational definition for the molecular target is:

“For purposes of section 505B of the FD&C Act, the Agency interprets a “molecular target” in cancer drug development as a molecule in human cells (normal or cancer cells) that is intrinsically associated with a particular malignant disease process such as etiology, progression, and/or drug resistance. For a molecule to be considered a molecular target for purposes of section 505B, there should be evidence that addressing the molecule with a drug produces a predictable therapeutic effect resulting in alteration of the disease process.” (Guidance at 125)

FDA will make the determination as to whether a molecular target is substantially relevant to the growth or progression of pediatric cancer:

FDA is responsible for determining whether a molecular target is substantially relevant for purposes of section 505B of the FD&C Act. Molecular targets that lack sufficient evidence for FDA to determine whether they are “substantially relevant” or “not substantially relevant” will not be included in a target list, however, the lists will be updated regularly to reflect additional determinations regarding the relevance of molecular targets. (Guidance at 138)

Initial target lists are available here.

Filing your iPSP waiver or deferral request

If you are planning to submit an iPSP waiver or deferral request, it is important to follow FDA filing guidelines. The iPSP for an anticipated NDA filing typically must be made within 60 calendar days after the end-of-phase 2 meeting or 210 days before the expected filing date of the NDA.

Premier Research has supported sponsors with the development of pediatric study plans to satisfy PREA, including waivers and deferrals, for more than 250 products. Contact us to learn more.