1551P - Breakthrough therapy cancer drugs and indications with FDA approval: Development time, innovation, trials, clinical benefit, epidemiology, and price

Background

The breakthrough therapy designation facilitates the development of drugs with a large preliminary benefit in treating serious or life-threatening diseases. This study analyzes the US Food and Drug Administration (FDA) approval, trials, benefits, unmet needs, and pricing of breakthrough therapy cancer drugs.

Methods

We analyzed 355 cancer indications with FDA approval (2012-2022). Breakthrough and non-breakthrough indications were compared regarding their FDA approval, innovativeness, trials, epidemiology, and price with data from FDA labels, Global Burden of Disease study, and Medicare & Medicaid. We meta-analyzed hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and relative risk rates (RR) and objective response rates (ORR) for tumor response.

Results

We identified 137 breakthrough and 218 non-breakthrough cancer indications. The median clinical development time was 3.2 years shorter for breakthrough drugs (5.6 vs. 8.8 years, p=.002). The breakthrough designation was more frequently granted to biomarker-directed indications (46% vs. 34%, p=.025) supported by smaller trials (median: 149 vs. 326 patients, p<.001) of single-arm (53% vs. 27%, p<.001) phase I/II design (61% vs. 31%, p<.001). Breakthrough indications offered a greater OS (HR: 0.69 vs. 0.74, p=.031) and tumor response (RR: 1.48 vs. 1.32, p=.006; ORR: 52% vs. 40%, p=.004), yet not PFS benefit (HR: 0.53 vs. 0.58, p=.212). Median improvements in OS (4.8 vs. 3.2 months, p=.004) and PFS (5.4 vs. 3.3 months, p=.005) were higher for breakthrough than non-breakthrough indications. The breakthrough designation was more frequently granted to first-in-class drugs (42% vs. 28%, p=.001) and first-in-indication treatments (43% vs. 29%, p<.001). There were no differences in the treatment and epidemiologic characteristics between breakthrough and non-breakthrough drugs. Breakthrough drugs were more expensive than non-breakthrough drugs (mean monthly price: $38,971 vs. $22,591, p=.0592).

Conclusions

The breakthrough therapy designation expedites patient access to effective and innovative, yet also expensive, new cancer drugs and indications.

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.