The US Food and Drug Administration (FDA) on Monday released new draft guidance to assist sponsors of treatments for rare diseases in planning and conducting more efficient and productive pre-investigational new drug application (pre-IND) meetings.
Specifically, the guidance discusses issues commonly encountered in the early phases of rare disease drug development.
“Our experience shows that early and substantive engagement with FDA review teams can help increase the quality of applications and the odds of success with development programs,” FDA Commissioner Scott Gottlieb said. “We encourage sponsors to engage the agency early in the regulatory process, especially when it comes to drugs targeted to rare conditions.”
The 15-page guidance focuses on various considerations including pharmaceutical quality, nonclinical, clinical pharmacology, clinical, and additional considerations on expedited programs, companion diagnostics, orphan product incentives and pediatric studies.
“A pre-IND meeting is often the first regulatory communication between the sponsor and FDA regarding the development program for an investigational drug or a new indication for an approved drug. During pre-IND meetings, sponsors can discuss with FDA the unique challenges of rare disease drug development and where regulatory flexibility can be justified,” the draft says.
Among the many challenges sponsors of treatments for rare diseases face is the small number of disease-affected individuals and the lack of understanding of the natural history of the disease, the draft notes, though because of the limitations in patient numbers, “It is important to maximize the contribution of each patient in the clinical development program.”
And while the approval standard for drugs treating rare diseases is the same as that for drugs treating non-rare diseases, FDA says it is appropriate to exercise the broadest possible scientific judgment in applying the evidentiary standard in the rare disease setting.
“To that end, FDA will consider: (1) benefits and risks of the drug; (2) seriousness of the disease; and (3) if there is an unmet medical need. This approach reflects FDA’s recognition that patients and physicians are generally willing to accept greater risks and side effects from treatment of life-threatening and severely debilitating diseases than they would for other diseases,” the draft guidance says.
The draft also notes that FDA recommends that sponsors discuss drug diagnostic co-development early in the drug development program if the drug “is likely to only have a favorable benefit-risk profile in a biomarker-defined subtype of patients.”
Rare Diseases: Early Drug Development and the Role of Pre-IND Meetings: Draft Guidance for Industry