1705P - Therapeutic value of first vs supplemental indications of drugs in the US and Europe (2011-2020): Retrospective cohort study

Background

After first approval of a new drug, it may subsequently be approved for additional indications. The number of drugs approved for such supplemental indications has increased, however, their added therapeutic benefit is unclear. We analyzed the therapeutic value of supplemental indications compared to first indications for drugs approved in the US and Europe (2011-2020).

Methods

We identified first and supplemental indications that were approved by the FDA and EMA. Therapeutic value ratings were obtained from France and Germany. We used descriptive statistics to analyze the unadjusted proportion of first and supplemental indications rated highly by the French or German health authorities. To obtain adjusted estimates of the probability for supplemental indications to be rated highly, we used Poisson regression analyses.

Results

124 first and 335 supplemental indications approved by the FDA, and 88 first and 215 supplemental indications by the EMA were included, the largest subset for cancer disorders. Therapeutic ratings were available for 107 (86%) first and 179 (53%) supplemental indications in the US, and 87 (99%) first and 184 (86%) supplemental indications in Europe. Among FDA-approved indications with available ratings, 41% (44/107) had high therapeutic value ratings for first, compared with 34% (61/179) for supplemental indications. In Europe, 47% (41/87) of first and 36% (67/184) of supplemental indications had high therapeutic value ratings. Among FDA approvals, when the sample was restricted to the first three approved indications, second indication approvals were 36% less likely to have a high value rating (RR=0.64, 95%CI, 0.43-0.96) and third indication approvals were 45% less likely (RR=0.55, 95%CI, 0.29-1.01) when compared to the first indication approval. Similar findings were observed for Europe and when weighting by the inverse number of indications for each drug.

Conclusions

The proportion of supplemental indications rated as having high therapeutic value was substantially lower compared to first indications. When indications do not offer added therapeutic value over other available treatments, that information should be clearly communicated to patients and physicians.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

K.N. Vokinger.

Funding

Swiss Cancer Research Foundation, Swiss National Science Foundation.

Disclosure

All authors have declared no conflicts of interest.