Monday April 26, 2021 - A small flurry of public policy documents or articles relevant to precision medicine.
FDA Reviewing a Set of ImmunoOncology Drugs in Advisory Meetings
This week the FDA is holding panels on a substantial cohort of oncology drugs which each have indications in the "limbo" between somewhat aging accelerated approvals and conversion to full approvals.
Recall that accelerated approvals may be based on single-arm trials and surrogate biomarkers (like tumor response), as long as there is unmet need and the drug seems promising.
FDA Places Article on Accelerated Approvals in the NEJM
Timed to the FDA meetings, see an article in NEJM by Julia Beaver and Richard Pazdur; Pazdur is the longtime head of Oncology at FDA. Here. The article is called " 'Dangling' Accelerated Approvals in Oncology."
A table includes 3 "dangling" approvals for atezolizumab, 4 for pembrolizumab, 2 for nivolumab, and 1 for durvalumab.
Authors note that a failure of the follow-up confirmatory trial need not be fatal, but the circumstances need to be evaluated carefully when that occurs. In addition, the evolving status of "unmet need" for that indication needs to be evaluated as well.
I consider this a precision medicine issue; most accelerated approvals are in oncology and of that, many in immunooncology. The status and performance of immuno-oncology biomarkers (TMB, PDL1, MSI, and others) remains very much in evolution (see section ImmunoOncology Biomarkers at bottom.)
ICER Releases Stringent Suggestions to Improve "Accelerated Approval"
Separately, see a brand new 40-page white paper by ICER on "Strengthening the Accelerated Approval Pathway," which mostly takes the form of describing holes and weaknesses in the accelerated approval pathway. Here.
Again, it's a precision oncology issue in as much as many accelerated approvals are in oncology and often involve biomarkers or surrogate outcomes. Topics covered in the 40-page review include:
- Manage uncertainty better: (1) Better Surrogate endpoint use; (2) Threshold for "meaningful change' in surrogate endpoint [e.g. 30% change in the endpoint, not 8%]; (3) Issues with lack of randomization (one arm studies).
- Process issues include: (1) delayed confirmatory studies, (2) Inconsistent decisions [one drug to the next]; (3) high prices of drugs with only conditional/accelerated approval.
- Proposals for FDA's adoption include: Use standard templates for info [promotes comparability and uniform processes in review]; greater use of RCTs instead of single-arms; robust requirements to finish confirmatory trials; sunset rules.
- Payment ideas include: Mandatory rebates for drugs sold under "accelerated approval," or sale only at "marginal cost price" or under "outcomes based contracts." (Note that laws for payment issues are generate separate from laws for FDA approval issues.)