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Fifteen years of clinical trials in Huntington’s disease: a very low clinical drug development success rate

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dc.contributor.authorTravessa, André
dc.contributor.authorRodrigues, Filipe Brogueira
dc.contributor.authorMestre, Tiago
dc.contributor.authorFerreira, Joaquim J
dc.date.accessioned2022-02-18T16:14:41Z
dc.date.available2022-02-18T16:14:41Z
dc.date.issued2017
dc.description© 2017 – IOS Press and the authors. All rights reservedpt_PT
dc.description.abstractBackground: Drug development in Huntington's disease (HD) is particularly challenging, and only two compounds are approved by the FDA. It is therefore essential to appraise drug development programs in order to understand the reasons for their failure during the early stages of development. Objectives: To describe the landscape of HD therapeutic development and critically explore the causes of compound attrition in the different stages of drug development, from phase 1 to phase 4. Methods: All HD clinical trials registered in the WHO International Clinical Trials Search Portal, from inception to May 2017, were analyzed. Two independent authors selected and extracted data. Success rate in a trial phase was calculated as the number of compounds that progressed to the next trial phase divided by the number of compounds in that phase. The overall success rate was calculated as the ratio between the number of compounds that receive regulatory approval and the total number of compounds. Results: Ninety-nine trials assessing 41 compounds and eleven non-pharmacological interventions (devices and cell therapies) were identified. Twenty-four (24.2%) were phase 1 trials, 46 (46.5%) phase 2, 20 (20.2%) phase 3, and two (2.0%) phase 4. Sixty trials (60.6%) received industry sponsorship. The most frequently studied compounds were creatine, latrepirdine and pridopidine. The mean number of participants enrolled was 92.0 and the length of treatment was 262.9 days, and both increased from phase 1 to phase 3 trials. The success rate was 25.0% from phase 1 to phase 2, 19.4% from phase 2 to phase 3, and 14.3% from phase 3 to approval. The overall success rate was 3.5%. Conclusions: Although HD is a rare condition, 99 HD trials were identified in a comprehensive clinical trial registry. We found a low success rate at earlier phases of drug-development and a very low trial success rate at later phases. There is a significant gap between drug discovery and development success rates that warrants careful appraisal and improvement.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Huntingtons Dis. 2017;6(2):157-163pt_PT
dc.identifier.doi10.3233/JHD-170245pt_PT
dc.identifier.eissn1879-6400
dc.identifier.issn1879-6397
dc.identifier.urihttp://hdl.handle.net/10451/51424
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherIOS Presspt_PT
dc.relation.publisherversionhttps://www.iospress.com/catalog/journals/journal-of-huntingtons-diseasept_PT
dc.subjectClinical developmentpt_PT
dc.subjectClinical trialspt_PT
dc.subjectHuntington diseasept_PT
dc.subjectMedicinespt_PT
dc.titleFifteen years of clinical trials in Huntington’s disease: a very low clinical drug development success ratept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage163pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage157pt_PT
oaire.citation.titleJournal of Huntington's Diseasept_PT
oaire.citation.volume6pt_PT
person.familyNameTravessa
person.familyNameRodrigues
person.familyNameMestre
person.familyNameFerreira
person.givenNameAndré
person.givenNameFilipe Brogueira
person.givenNameTiago
person.givenNameJoaquim J
person.identifier1624753
person.identifier.ciencia-id0813-5196-99F5
person.identifier.ciencia-id7D15-5CD6-6159
person.identifier.orcid0000-0002-4147-2800
person.identifier.orcid0000-0002-5567-7938
person.identifier.orcid0000-0002-6973-7479
person.identifier.orcid0000-0003-3950-5113
person.identifier.ridR-2679-2017
person.identifier.scopus-author-id56998766700
person.identifier.scopus-author-id57191254295
person.identifier.scopus-author-id16242276700
person.identifier.scopus-author-id7403252466
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationc68899fe-1072-451b-ae27-81bdca4daf77
relation.isAuthorOfPublication5c6a1722-1b5e-432c-b21d-8ce9d9a29c5a
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relation.isAuthorOfPublication54d84fe7-2cbd-4ddc-bce2-0ff2bd7c4cc9
relation.isAuthorOfPublication.latestForDiscoveryc68899fe-1072-451b-ae27-81bdca4daf77

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