The US Food and Drug Administration (FDA) tends to approve cancer drugs faster than other regulatory agencies, but there is no association between faster regulatory review and high clinical benefit, new research suggests.
From 2007 to 2020, 80% of the approved cancer drugs were first approved by the FDA, and 91% of the FDA-approved drugs were eligible for some type of expedited review.
However, there was no evidence linking quicker review times with high clinical benefit for the FDA or for most of the other regulatory agencies evaluated. Researchers reported these findings in JCO Oncology Practice.
The aim of this study was to assess trends in regulatory review times for the FDA, European Medicines Agency (EMA), Switzerland’s Swissmedic, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), Health Canada, and Australia’s Therapeutic Goods Administration (TGA).
Researchers identified all new cancer drug approvals by these agencies between January 2007 and May 2020. There were 128 drugs that were granted initial regulatory approval by at least 1 agency. Of these drugs, 60% were approved for solid tumors and 40% were for hematologic malignancies.
All 6 of the regulatory agencies had approved 45% of the drugs by May 2020, but 20% of the drugs were approved by just 1 agency.
Most drugs were first approved by the FDA (80%), followed by PMDA (9%), EMA (8%), Swissmedic (2%), and TGA (2%). Health Canada did not grant the initial approval for any of the drugs.
Review Times and Expedited Review
Most drugs approved by the FDA (91%) and Health Canada (59%) qualified for at least 1 expedited review program. However, most drugs approved by the EMA (64%), PMDA (82%), and TGA (94%) were not eligible for expedited review. Expedited programs for the TGA came into effect in 2017, and data were not available for Swissmedic.
The median review times ranged from 6 months to 10 months for the FDA, 9.7-14.9 months for the EMA, 6-10.5 months for the PMDA, 7.3-11.5 months for Health Canada, and 6.2-12 months for the TGA.
For the 102 drugs that were first approved by the FDA, the median time to subsequent approval was 9.7 months for the EMA, 12.2 months for Health Canada, 15.7 months for Swissmedic, 17.1 months for the TGA, and 37.4 months for the PMDA.
“For regulators other than the FDA and EMA, delays in submission of regulatory applications by manufacturers accounted for a significant portion of the time to subsequent approval,” the researchers wrote.
The researchers assessed clinical benefit using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the American Society of Clinical Oncology Cancer Research Committee (ASCO-CRC) tool.
Overall, when the researchers used ESMO-MCBS, high clinical benefit was not associated with total review times. Drugs considered to have a high clinical benefit were associated with shorter review times for Health Canada (–1.90 months; P =.03) but not for the FDA (P =.90), the EMA (P =.32), the PMDA (P =.83), or the TGA (P =.57). Data for Swissmedic were not available.
Using ESMO-MCBS, subsequent review times after FDA approval were significantly shorter for drugs with higher clinical benefit for the EMA (P =.006) and Swissmedic (P =.02) but not for the PMDA (P =.21), Health Canada (P =.05), or the TGA (P =.09).
Using ASCO-CRC, there was no association between high clinical benefit and total review times or time to subsequent approval for any of the regulatory agencies.
The researchers concluded that there is “little evidence that expedited programs successfully prioritized drugs with high clinical benefit, including, notably, the breakthrough therapy program in the United States.”
“These findings may reflect uncertainty or lack of systematic definition of the level of benefit expected for drugs qualifying for faster clinical development or regulatory review,” the researchers wrote. “Aligning reviews with health technology assessment
agencies, such as in Canada and in the EU, and using a validated value framework, such as ESMO’s MCBS, may help raise the bar for expedited programs in general so that regulators can deploy limited time and resources most efficiently.”
Disclosures: This research was supported by several organizations. One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Hwang TJ, Kesselheim AS, Tibau A, Lee CWC, Vokinger KN. Clinical benefit and expedited approval of cancer drugs in the United States, European Union, Switzerland, Japan, Canada, and Australia. JCO Oncol Pract. Published online June 22, 2022. doi:10.1200/OP.21.00909