Table 3.
Univariate Comparison between Initial and Supplementary Indication Approval of New Targeted Multi-Indication Cancer Drugs by the FDA, EMA, HC, and TGA
|
Initial Indication |
Supplementary Indication |
Univariate | |||||
|---|---|---|---|---|---|---|---|
| No | (%) | No | (%) | OR | [95% CI] | P-value | |
| A) Regulatory Approval | |||||||
| Approval Type | |||||||
| Standard | 48 | (50.0%) | 191 | (73.2%) | 1.00 | [Reference] | |
| Conditional Approval | 29 | (30.2%) | 37 | (14.2%) | 3.89 | [1.65–9.17] | 0.002 |
| Priority Review | 19 | (19.8%) | 33 | (12.6%) | 2.75 | [1.25–6.04] | 0.012 |
| Orphan Designation | |||||||
| No | 54 | (56.2%) | 203 | (77.8%) | 1.00 | [Reference] | |
| Yes | 42 | (43.8%) | 58 | (22.2%) | 2.72 | [1.33–5.57] | 0.006 |
| MA Supporting Trial † | |||||||
| No | 30 | (31.2%) | 150 | (57.4%) | 1.00 | [Reference] | |
| Phase 1 | 4 | (4.2%) | 24 | (9.2%) | 0.92 | [0.30–2.78] | 0.882 |
| Phase 2 | 31 | (32.3%) | 44 | (16.9%) | 3.75 | [1.62–8.70] | 0.002 |
| Phase 3 | 31 | (32.3%) | 43 | (16.5%) | 3.83 | [1.54–9.52] | 0.004 |
| B) Pivotal Trial Characteristics | |||||||
| Trial Design ‡ | |||||||
| Phase 1 | 8 | (8.3%) | 7 | (2.7%) | 1.00 | [Reference] | |
| Phase 2 | 31 | (32.3%) | 54 | (20.7%) | 0.50 | [0.07–3.66] | 0.495 |
| Phase 3 | 57 | (59.4%) | 200 | (76.6%) | 0.25 | [0.04–1.59] | 0.140 |
| Primary Endpoint | |||||||
| Surrogate | 70 | (72.9%) | 167 | (64.0%) | 1.00 | [Reference] | |
| Clinical | 20 | (20.8%) | 43 | (16.5%) | 1.11 | [0.36–3.44] | 0.859 |
| Co-Primary | 6 | (6.3%) | 51 | (19.5%) | 0.28 | [0.06–1.34] | 0.112 |
| MCBS Score | |||||||
| Score of 1, 2, or 3 | 40 | (41.7%) | 159 | (60.9%) | 1.00 | [Reference] | |
| Score of 4 or 5 | 56 | (58.3%) | 102 | (39.1%) | 2.20 | [0.94–5.16] | 0.070 |
| Enrolled Patients (per 100) | |||||||
| Mean [95% CI] | 547 | [465–629] | 585 | [533–637] | 0.98 | [0.88–1.09] | 0.687 |
| Trial Length (months) | |||||||
| Mean [95% CI] | 29 | [26–32] | 34 | [31–36] | 0.98 | [0.95–1.01] | 0.189 |
| C) Treatment Characteristics | |||||||
| Treatment Type | |||||||
| Combination | 4 | (4.2%) | 55 | (21.1%) | 1.00 | [Reference] | |
| Monotherapy | 92 | (95.8%) | 206 | (78.9%) | 6.17 | [1.20–31.8] | 0.030 |
| Line of Treatment | |||||||
| 2nd, 3rd, or 4th Line | 68 | (70.8%) | 153 | (58.6%) | 1.00 | [Reference] | |
| 1st Line | 28 | (29.2%) | 108 | (41.4%) | 0.58 | [0.22–1.55] | 0.279 |
| Multi-Indication Drug Type | |||||||
| Across Therapeutic Areas | 20 | (20.8%) | 50 | (19.2%) | 1.00 | [Reference] | |
| Across Disease Areas | 38 | (39.6%) | 160 | (61.3%) | 0.59 | [0.17–2.04] | 0.409 |
| Across Lines of Therapy | 38 | (39.6%) | 51 | (19.5%) | 1.86 | [0.50–6.97] | 0.355 |
Indication approval sequence was determined by the FDA approval date (initial indication: 1, subsequent indication: 0). MCBS: Magnitude of Clinical Benefit Scale (1: low benefit to 5: high benefit)
† Highest phase of supporting trials disclosed in the regulatory approval report
‡ Highest phase pivotal trial disclosed in the regulatory approval report