title: The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development.
abstract: Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD.We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme.To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics.Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to market.
authors.affiliation: Newcastle University, Newcastle upon Tyne, UK. Emma.Heslop@ncl.ac.uk.
authors.forename: Emma
authors.initials: E
authors.lastname: Heslop
authors.affiliation: Cydan Developments Inc, Cambridge, USA. ccsimma@CydanCo.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Csimma
authors.affiliation: Newcastle University, Newcastle upon Tyne, UK. volker.straub@newcastle.ac.uk.
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.affiliation: PharMac LLL, Boca Grande, USA. john.m.mccall@pharmacllc.com.
authors.forename: John
authors.initials: J
authors.lastname: McCall
authors.affiliation: Children's National Medical Center, Washington, USA. knagaraju@cnmcresearch.org.
authors.forename: Kanneboyina
authors.initials: K
authors.lastname: Nagaraju
authors.affiliation: Johns Hopkins University, Baltimore, USA. wagnerk@kennedykrieger.org.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Wagner
authors.affiliation: Genethon, Evry, France. caizerg@genethon.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Caizergues
authors.affiliation: University of Freiburg, Freiburg, Germany. rudolf.korinthenberg@uniklinik-freiburg.de.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Korinthenberg
authors.affiliation: Nationwide Children's Hospital, Columbus, USA. kevin.flanigan@nationwidechildrens.org.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Flanigan
authors.affiliation: National Institutes of Health, Washington, USA. Petra.Kaufman@nih.gov.
authors.forename: Petra
authors.initials: P
authors.lastname: Kaufmann
authors.affiliation: National Institutes of Health, Washington, USA. mcneilde@ninds.nih.gov.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McNeil
authors.affiliation: Nationwide Children's Hospital, Columbus, USA. Jerry.Mendell@nationwidechildrens.org.
authors.forename: Jerry
authors.initials: J
authors.lastname: Mendell
authors.affiliation: Parent Project Muscular Dystrophy, New Jersey, USA. sharon.hesterlee@myotonic.org.
authors.forename: Sharon
authors.initials: S
authors.lastname: Hesterlee
authors.affiliation: Royal Veterinary College, London, UK. dwells@rvc.ac.uk.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Wells
authors.affiliation: Newcastle University, Newcastle upon Tyne, UK. Kate.Bushby@ncl.ac.uk.
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
mesh_terms: D026683:Advisory Committees; D000818:Animals; D006801:Humans; D009468:Neuromuscular Diseases / Q000188:drug therapy; D009965:Orphan Drug Production; D035583:Rare Diseases / Q000188:drug therapy; D014481:United States