1706P - Time to full approval of novel anticancer medicines granted accelerated approval and implications for reform of the accelerated approval pathway

Background

The Accelerated Approval (AA) pathway was established to speed development and approval of drugs for life-threatening conditions with limited treatment options. In December 2022, the US Congress enacted new policies to ensure that confirmatory studies for AA medicines are completed in a timely fashion. Here, we evaluate factors associated with conversion of AA to regular approval by the US FDA, including magnitude of clinical benefit as measured by European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).

Methods

We included all anticancer drugs that had received AA from the US FDA from 1992 to 2020, with follow up on approval status through January 2022. FDA drug labels and clinical trial reports were reviewed to apply ESMO-MCBS v1.1 grades to both initial and confirmatory studies. High clinical benefit was defined as a grade of A or B for trials of curative intent and 4 or 5 for those of palliative intent. Withdrawn AA indications, as determined by FDA, were considered as low benefit.

Results

From 1992 to 2020, the FDA granted AA to 46 anticancer solid drugs for 74 indications. The median time between AA and regular approval of oncology drugs was 3.7 years (range: 0.8-12.6 years). Of these 74 indications, 42 (57%) had clinical benefit confirmed in post-approval clinical trials and were converted to regular approval. Indications with high clinical benefit according to ESMO-MCBS were associated with shorter times to conversion to regular approval (median 2.5 vs 4.8 years; P=0.007). Similarly, indications with overall survival benefit were associated with shorter times to regular approval (median 2.6 vs 3.7 years; P=0.04).

Conclusions

Anticancer medicines with greater clinical benefit were associated with faster conversion to full FDA approval. New policy reforms to the AA pathway in the USA should prioritize further expediting market access of therapies with high clinical benefit as well as expedited completion of confirmatory studies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.