FDA approval, clinical trial evidence, efficacy, epidemiology, and price for non-orphan and ultra-rare, rare, and common orphan cancer drug indications: cross sectional analysis
Objective: To analyze the US Food and Drug Administration (FDA) approval, trials, unmet needs, benefit, and pricing of ultra-rare (<6600 affected US citizens), rare (6600-200 000 citizens), and common (>200 000 citizens) orphan cancer drug indications and non-orphan cancer drug indications. De...
Gespeichert in:
| Hauptverfasser: | , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
09 May 2023
|
| In: |
The BMJ
Year: 2023, Jahrgang: 381, Pages: 1-12 |
| ISSN: | 1756-1833 |
| DOI: | 10.1136/bmj-2022-073242 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1136/bmj-2022-073242 Verlag, kostenfrei, Volltext: https://www.bmj.com/content/381/bmj-2022-073242 
|
| Verfasserangaben: | Thomas Michaeli, Hendrik Jürges, Daniel Tobias Michaeli |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1851557075 | ||
| 003 | DE-627 | ||
| 005 | 20250422115636.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230704s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1136/bmj-2022-073242 |2 doi | |
| 035 | |a (DE-627)1851557075 | ||
| 035 | |a (DE-599)KXP1851557075 | ||
| 035 | |a (OCoLC)1389527846 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Michaeli, Christoph T. |d 1992- |e VerfasserIn |0 (DE-588)1277182337 |0 (DE-627)1830343769 |4 aut | |
| 245 | 1 | 0 | |a FDA approval, clinical trial evidence, efficacy, epidemiology, and price for non-orphan and ultra-rare, rare, and common orphan cancer drug indications |b cross sectional analysis |c Thomas Michaeli, Hendrik Jürges, Daniel Tobias Michaeli |
| 264 | 1 | |c 09 May 2023 | |
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 04.07.2023 | ||
| 520 | |a Objective: To analyze the US Food and Drug Administration (FDA) approval, trials, unmet needs, benefit, and pricing of ultra-rare (<6600 affected US citizens), rare (6600-200 000 citizens), and common (>200 000 citizens) orphan cancer drug indications and non-orphan cancer drug indications. Design Cross sectional analysis: Setting Data from DrugsFDA, FDA labels, Global Burden of Disease study, and Medicare and Medicaid. Population: 170 FDA approved drugs across 455 cancer indications between 2000 and 2022. Main outcome measures: Comparison of non-orphan and ultra-rare, rare, and common orphan indications regarding regulatory approval, trials, epidemiology, and price. Hazard ratios for overall survival and progression-free survival were meta-analyzed. Results: 161 non-orphan and 294 orphan cancer drug indications were identified, of which 25 were approved for ultra-rare diseases, 205 for rare diseases, and 64 for common diseases. Drugs for ultra-rare orphan indications were more frequently first in class (76% v 48% v 38% v 42%; P<0.001), monotherapies (88% v 69% v 72% v 55%; P=0.001), for hematologic cancers (76% v 66% v 0% v 0%; P<0.001), and supported by smaller trials (median 85 v 199 v 286 v 521 patients; P<0.001), of single arm (84% v 44% v 28% v 21%; P<0.001) phase 1/2 design (88% v 45% v 45% v 27%; P<0.001) compared with rare and common orphan indications and non-orphan indications. Drugs for common orphan indications were more often biomarker directed (69% v 26% v 12%; P<0.001), first line (77% v 39% v 20%; P<0.001), small molecules (80% v 62% v 48%; P<0.001) benefiting from quicker time to first FDA approval (median 5.7 v 7.1 v 8.9 years; P=0.02) than those for rare and ultra-rare orphan indications. Drugs for ultra-rare, rare, and common orphan indications offered a significantly greater progression-free survival benefit (hazard ratio 0.53 v 0.51 v 0.49 v 0.64; P<0.001), but not overall survival benefit (0.50 v 0.73 v 0.71 v 0.74; P=0.06), than non-orphans. In single arm trials, tumor response rates were greater for drugs for ultra-rare orphan indications than for rare or common orphan indications and non-orphan indications (objective response rate 57% v 48% v 55% v 33%; P<0.001). Disease incidence/prevalence, five year survival, and the number of available treatments were lower, whereas disability adjusted life years per patient were higher, for ultra-rare orphan indications compared with rare or common indications and non-orphan indications. For 147 on-patent drugs with available data in 2023, monthly prices were higher for ultra-rare orphan indications than for rare or common orphan indications and non-orphan indications ($70 128 (£55 971; €63 370) v $33 313 v $16 484 v $14 508; P<0.001). For 48 on-patent drugs with available longitudinal data from 2005 to 2023, prices increased by 94% for drugs for orphan indications and 50% for drugs for non-orphan indications on average.Conclusions: The Orphan Drug Act of 1983 incentivizes development of drugs not only for rare diseases but also for ultra-rare diseases and subsets of common diseases. These orphan indications fill significant unmet needs, yet their approval is based on small, non-robust trials that could overestimate efficacy outcomes. A distinct ultra-orphan designation with greater financial incentives could encourage and expedite drug development for ultra-rare diseases. | ||
| 700 | 1 | |a Jürges, Hendrik |e VerfasserIn |0 (DE-588)122315731 |0 (DE-627)521405971 |0 (DE-576)293215847 |4 aut | |
| 700 | 1 | |a Michaeli, Daniel |d 1997- |e VerfasserIn |0 (DE-588)1277183244 |0 (DE-627)1830345109 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The BMJ |d London : BMJ Publ. Group, 1988 |g 381(2023), Artikel-ID e073242, Seite 1-12 |h Online-Ressource |w (DE-627)271349190 |w (DE-600)1479799-9 |w (DE-576)078590574 |x 1756-1833 |7 nnas |a FDA approval, clinical trial evidence, efficacy, epidemiology, and price for non-orphan and ultra-rare, rare, and common orphan cancer drug indications cross sectional analysis |
| 773 | 1 | 8 | |g volume:381 |g year:2023 |g elocationid:e073242 |g pages:1-12 |g extent:12 |a FDA approval, clinical trial evidence, efficacy, epidemiology, and price for non-orphan and ultra-rare, rare, and common orphan cancer drug indications cross sectional analysis |
| 856 | 4 | 0 | |u https://doi.org/10.1136/bmj-2022-073242 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.bmj.com/content/381/bmj-2022-073242 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20230704 | ||
| 993 | |a Article | ||
| 994 | |a 2023 | ||
| 998 | |g 1277183244 |a Michaeli, Daniel |m 1277183244:Michaeli, Daniel |d 60000 |e 60000PM1277183244 |k 0/60000/ |p 3 |y j | ||
| 998 | |g 1277182337 |a Michaeli, Christoph T. |m 1277182337:Michaeli, Christoph T. |d 60000 |d 61400 |e 60000PM1277182337 |e 61400PM1277182337 |k 0/60000/ |k 1/60000/61400/ |p 1 |x j | ||
| 999 | |a KXP-PPN1851557075 |e 4348177228 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"id":{"doi":["10.1136/bmj-2022-073242"],"eki":["1851557075"]},"recId":"1851557075","name":{"displayForm":["Thomas Michaeli, Hendrik Jürges, Daniel Tobias Michaeli"]},"relHost":[{"recId":"271349190","id":{"eki":["271349190"],"zdb":["1479799-9"],"issn":["1756-1833"]},"part":{"text":"381(2023), Artikel-ID e073242, Seite 1-12","year":"2023","extent":"12","pages":"1-12","volume":"381"},"physDesc":[{"extent":"Online-Ressource"}],"disp":"FDA approval, clinical trial evidence, efficacy, epidemiology, and price for non-orphan and ultra-rare, rare, and common orphan cancer drug indications cross sectional analysisThe BMJ","titleAlt":[{"title":"BMJ. British medical journal (Clinical research ed.)"}],"language":["eng"],"pubHistory":["297.1988 -"],"title":[{"title_sort":"BMJ","title":"The BMJ"}],"origin":[{"dateIssuedKey":"1988","publisherPlace":"London","dateIssuedDisp":"1988-","publisher":"BMJ Publ. Group"}],"type":{"bibl":"periodical","media":"Online-Ressource"},"note":["Gesehen am 02.10.20"]}],"physDesc":[{"extent":"12 S."}],"language":["eng"],"title":[{"title":"FDA approval, clinical trial evidence, efficacy, epidemiology, and price for non-orphan and ultra-rare, rare, and common orphan cancer drug indications","subtitle":"cross sectional analysis","title_sort":"FDA approval, clinical trial evidence, efficacy, epidemiology, and price for non-orphan and ultra-rare, rare, and common orphan cancer drug indications"}],"person":[{"role":"aut","display":"Michaeli, Christoph T.","family":"Michaeli","given":"Christoph T."},{"role":"aut","display":"Jürges, Hendrik","family":"Jürges","given":"Hendrik"},{"family":"Michaeli","given":"Daniel","display":"Michaeli, Daniel","role":"aut"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"origin":[{"dateIssuedDisp":"09 May 2023","dateIssuedKey":"2023"}],"note":["Gesehen am 04.07.2023"]} | ||
| SRT | |a MICHAELICHFDAAPPROVA0920 | ||