RE:RE:Clinical Trial Size in Orphan and Rare Diseases
Accelerated Approval Pathway
For rare disease patients, time is always of the essence. Many rare diseases progress quickly and, moreover, delayed treatment only increases the economic burden on families. However, many patients with rare conditions have obtained faster access to treatments that provide meaningful advantages through FDA’s Accelerated Approval pathway. Congress established the pathway in 1992 to expedite the approval and availability of drugs and biologics intended to treat serious and lifethreatening diseases and conditions for which there are unmet medical needs. Products seeking Accelerated Approval rely on surrogate endpoints, or markers, “such as a ORR, and PFS.” These endpoints can be measured effectively over a shorter period of time in smaller studies.
Following Accelerated Approvals based on surrogate endpoints, drug developers also are required to conduct studies — phase 4 confirmatory trials — to confirm the clinical benefit of the medicine. Once confirmed, the FDA will grant traditional approval for the treatment.
Accelerated Approval Pathway is supported in ASCO Educational Material on Approval of New Agents after Phase II Trials
“ Recent developments in cancer drug discovery have only heightened interest in earlier approval. The rapid expansion of knowledge regarding the genetic basis of cancer has revealed specific molecular targets that underlie common malignancies. At the same time, major categories of disease, such as lung and colorectal cancer, once thought to be relatively homogeneous, are now recognized as encompassing a number of unique molecular entities, and in selected cases, these entities respond to treatments that target the underlying mutations. Thus, mutated receptor tyrosine kinases and activated intracellular signaling pathways have become rational targets for experimental cancer therapies, and their early application in carefully selected subsets of patients has met with impressive success. The widespread adoption of this “targeted” approach, called personalized or precision medicine, has had immediate consequences for cancer drug development and approval.
Biomarker assay, for patient selection, is an essential requirement for rapid drug development and early approval.
In many types of cancer, a strong indication of activity, such as a 50 percent or greater partial and complete response rate coupled with a time to progression of 4 to 6 months or greater, would represent a significant step forward [in granting accelerated approval] and need not require preapproval confirmation in a phase III trial, particularly if no standard therapy provides benefit. One can imagine many such disease entities, including grade glioblastomas, metastatic pancreatic cancer, metastatic cholangiocarcinoma, hepatoma, and various subsets of soft tissue sarcoma, in which standard therapies are minimally active and significantly toxic.“
https://ascopubs.org/doi/full/10.14694/EdBook_AM.2012.32.114