BTD/AA Seems like a great fit for us...?
Accelerated Approval
In the manuscript entitled “Reevaluating the Accelerated Approval Process for Oncology Drugs”, the authors noted that under the current framework accelerated approval is generally pursued in heavily pretreated patients to qualify for the criteria of unmet medical need.(3) This population, however, may not be representative of the more general disease population. For example, treatment-refractory tumors may exhibit resistance mechanisms that arise from defined molecular aberrations. The authors proposed key recommendations with the intent of moving accelerated approval into earlier treatment settings and encouraging a diversity of agents targeting distinct pathways. Key recommendations include:
These proposed changes may induce a paradigm shift in oncology drug development. For example, drugs targeting novel molecular pathways may be approved without the conventional comparative trials against standard therapy. Likewise, different agents targeting distinct pathways in the same disease subtype may also be considered for approval without direct comparison or combination studies. In all cases, plans for confirmatory or post-marketing studies should be in place.
Breakthrough Therapy Designation
The Advancing Breakthrough Therapies for Patients Act was enacted in 2012 to expedite the development of drugs intended to treat a serious or life-threatening disease, with preliminary clinical evidence suggesting substantial improvement over existing therapies. In the manuscript entitled “Developing Standards for Breakthrough Therapy Designation in Oncology,” the authors propose criteria for the Breakthrough designation and pathways for the development of drugs where “unprecedented efficacy” signals are observed in early clinical trials.(3) The authors propose:
-
In the case of no standard of care, a Phase Ib expansion cohort or single arm pivotal trial could lead to full or accelerated approval.
-
Where early data suggests substantial improvement in efficacy compared to standard of care, a randomized phase II trial could support full approval.
Implications for study design
Both Accelerated Approval and Breakthrough Therapy designation offer the opportunity of expediting drug development through the use of smaller phase II studies with intermediate endpoints. In the case of Breakthrough Therapy, the potential of exploiting a Phase Ib expansion cohort or full approval without commitment for confirmatory phase III studies is also discussed. While these needed changes will no doubt hasten the pace of drug development, the implications for study design warrant consideration.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167364/