Table 2.
Characteristics of non-orphan and ultra-rare, rare, and common orphan cancer drug indications approved by US Food and Drug Administration (FDA) from 2000 to 2022. Values are numbers (percentages) unless stated otherwise
| Non-orphan (n=161; 37.4%) | Orphan | P value* | |||
|---|---|---|---|---|---|
| Common (n=64; 14.9) | Rare (n=205; 47.7%) | Ultra-rare (n=25; 5.8%) | |||
| Drug characteristics | |||||
| No of indications: | 0.08 | ||||
| Single indication | 19 (12) | 14 (22) | 37 (18) | 7 (28) | |
| Multi-indication | 142 (88) | 50 (78) | 168 (82) | 18 (72) | |
| Innovativeness: | 0.006 | ||||
| Not first in class | 93 (58) | 40 (63) | 106 (52) | 6 (24) | |
| First in class | 68 (42) | 24 (38) | 99 (48) | 19 (76) | |
| Mechanism of action: | <0.001 | ||||
| Cytotoxic chemotherapy | 11 (7) | 0 (0) | 21 (10) | 0 (0) | |
| Targeted agents | 91 (57) | 54 (84) | 115 (56) | 13 (52) | |
| Immune regulators | 59 (37) | 10 (16) | 69 (34) | 12 (48) | |
| Product type | <0.001 | ||||
| Small molecule | 73 (45) | 51 (80) | 126 (61) | 12 (48) | |
| Antibody | 79 (49) | 12 (19) | 57 (28) | 7 (28) | |
| Antibody-drug conjugate | 8 (5) | 0 (0) | 12 (6) | 3 (12) | |
| Other† | 1 (1) | 1 (26) | 10 (5) | 3 (12) | |
| Indication characteristics | |||||
| FDA approval type: | 0.005 | ||||
| Original indication | 50 (31) | 35 (55) | 82 (40) | 13 (52) | |
| Supplemental indication | 111 (69) | 29 (45) | 123 (60) | 12 (48) | |
| Treatment type: | 0.001 | ||||
| Combination therapy | 73 (45) | 18 (28) | 63 (31) | 3 (12) | |
| Monotherapy | 88 (55) | 46 (729) | 142 (69) | 22 (88) | |
| Cancer type: | <0.001 | ||||
| Hematologic | 0 (0) | 0 (0) | 135 (66) | 19 (76) | |
| Solid | 161 (100) | 64 (100) | 70 (34) | 6 (24) | |
| Biomarker: | <0.001 | ||||
| No | 95 (59) | 20 (31) | 151 (74) | 22 (88) | |
| Yes | 66 (41) | 44 (69) | 54 (26.3) | 3 (12) | |
| Line of therapy: | <0.001 | ||||
| First line | 84 (52) | 49 (77) | 79 (39) | 5 (20) | |
| Second line | 69 (43) | 15 (23) | 84 (41) | 15 (60) | |
| ≥Third line | 8 (5) | 0 (0) | 42 (20) | 5 (20) | |
| Clinical trial characteristics | |||||
| Median (IQR) enrolled patients | 521 (219-793) | 286 (122-505) | 199 (98-447) | 85 (53-124) | <0.001 |
| Clinical trial phase: | <0.001 | ||||
| Phase 1 | 6 (4) | 5 (8) | 9 (4) | 1 (4) | |
| Phase 2 | 38 (24) | 24 (38) | 85 (41) | 21 (84) | |
| Phase 3 | 117 (73) | 35 (55) | 111 (54) | 3 (12) | |
| Trial design: | <0.001 | ||||
| Single arm | 34 (21) | 18 (28) | 90 (44) | 21 (84) | |
| Non-randomized | 1 (1) | 6 (9) | 1 (<1) | 0 (0) | |
| Concurrent RCT | 122 (76) | 38 (59) | 110 (54) | 4 (16) | |
| Dose comparison RCT | 4 (2) | 2 (3) | 4 (2) | 0 (0) | |
| Type of blinding: | 0.002 | ||||
| Open label | 109 (68) | 43 (67) | 162 (79) | 24 (96) | |
| Single blind | 0 (0) | 0 (0) | 1 (<1) | 0 (0) | |
| Double blind | 52 (32) | 21 (33) | 42 (20) | 1 (4) | |
| Clinical trial arms: | <0.001 | ||||
| 1 arm | 34 (21) | 18 (28) | 90 (44) | 21 (84) | |
| 2 arms | 121 (75) | 41 (64) | 111 (54) | 4 (16) | |
| ≥3 arms | 6 (4) | 5 (8) | 4 (2) | 0 (0) | |
| Total No of concurrent RCTs | 122 | 38 | 110 | 4 | |
| Comparator: | 0.62 | ||||
| Active agent | 51 (42) | 15 (39) | 37 (34) | 1 (25) | |
| Placebo/no treatment | 71 (59) | 23 (61) | 73 (66) | 3 (75) | |
| Endpoint for concurrent RCTs: | |||||
| Overall survival | 104 (85) | 25 (66) | 73 (66) | 2 (50) | 0.003 |
| Progression-free survival | 102 (84) | 29 (76) | 89 (81) | 2 (50) | 0.30 |
| Tumor response | 96 (79) | 31 (82) | 89 (81) | 3 (75) | 0.96 |
| Other | 17 (14) | 6 (16) | 11 (10) | 0 (0) | 0.62 |
| Cancer epidemiology | |||||
| Median (IQR) disease incidence‡ | 68.4 (18.8-77.6) | 25 (19.5-67.6) | 5.2 (1.5-8.2) | 0.9 (0.2-4.3) | <0.001 |
| Median (IQR) disease prevalence‡ | 117.8 (111.2-832.8) | 117.8 (111.2-198.6) | 15.3 (6.5-27.3) | 3.2 (0.9-15) | <0.001 |
| Median (IQR) DALYs per person | 7.1 (5.5-7.7) | 5.5 (3.8-16.4) | 12.1 (7.3-17.7) | 10 (10-10) | <0.001 |
| Median (IQR) YLL per person | 6.6 (4.8-7.2) | 4.8 (3.3-16.2) | 11.8 (6.8-17.4) | 9.3 (9.3-9.3) | <0.001 |
| Median (IQR) YLD per person | 0.5 (0.4-0.7) | 0.5 (0.2-0.5) | 0.5 (0.3-0.7) | 0.7 (0.7-0.7) | <0.001 |
| Median (IQR) 5 year survival rate, % | 76.4 (66.2-91.4) | 91.4 (25-95) | 65 (32.7-75.2) | 66.1 (50-75.2) | <0.001 |
| Median (IQR) No of available treatments | 18 (12-38) | 14 (14-38) | 15 (11-22) | 8 (7-17) | <0.001 |
DALY=disability adjusted life year; IQR=interquartile range; RCT=randomized controlled trial; YLD=years of healthy life lost due to disability; YLL=years of life lost due to premature death.
*
Fisher’s exact tests or Kruskal-Wallis tests.
†
Includes gene therapies, cell therapies, enzymes, and radionuclides.
‡
Disease incidence and prevalence rates per 100 000 US citizens.