Epidiolex Clinical Review Timeline

Chronicle of the development and US FDA review of GW Pharmaceutical's Epidiolex (cannabidiol) for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients ages 2 and older.

Date	Action
IND Chronology (#120,055)
11/14/2013	Orphan drug designation granted for the treatment of Dravet syndrome (DS)
2/11/2014	Type B Pre-IND Meeting to discuss clinical pharmacology issues, abuse potential data, and specific trial design concerns
2/27/2014	Orphan drug designation granted for the treatment of Lennox-Gastaut syndrome (LGS)
3/31/2014	IND submitted for a study of the safety and efficacy of cannabidiol in the treatment of convulsive seizures associated with Dravet syndrome
6/2/2014	Fast track designation granted
6/14/2014	Type C meeting (written responses only) to discuss nonclinical requirements, clinical pharmacology issues, abuse potential data, and specific trial design concerns
12/24/2014	Type C meeting (written responses only) to discuss issues regarding clinical pharmacology and abuse potential data
4/2015	GW begins Study 1423 evaluating safety and efficacy of cannabidiol in the treatment of drop seizures in patients with LGS
6/2015	GW begins Study 1414 evaluating safety and efficacy of cannabidiol in the treatment of drop seizures in patients with LGS
6/24/2015	Sponsor proposes proprietary name Epidiolex
8/12/2015	Type C Chemistry, Manufacturing, and Controls (CMC) meeting; Division of Medication Error Prevention and Analysis (DMEPA) raised concerns with sponsor's risk assessment and the proposed 1 mL and 5 mL oral syringes
10/22/2015	Type C meeting (written responses only) to discuss issues of pooled safety and efficacy analyses for two expected DS studies and two expected LGS studies
11/10/2015	FDA finds proprietary name Epidiolex unacceptable
2/19/2016	GW submits an updated use-related risk analysis and a human factors validation study protocol, eliminated 1 mL oral syringe
4/4/2016	GW submits new proposed proprietary name (redacted)
4/11/2016	DMEPA notes deficiencies in review of proposed human factors validation study protocol and provided recommendations to be implemented prior to conducting the human factors validation study
7/19/2016	Type B Pre-NDA Meeting; DNP says it is acceptable for GW to submit Studies 1414 and 1423 concurrently to support an indication for LGS
9/26/2016	FDA finds new proposed proprietary name conditionally acceptable
4/20/2017	Rare pediatric disease designation granted for LGS and DS
5/2/2017	Rolling NDA review request granted
NDA Chronology (#210,365)
8/4/2017	GW submits the results of their human factors validation study as part of their rolling submission
10/29/2017	NDA Submitted
12/20/2017	NDA designated for priority review
12/20/2017	Botanical Review Team (BRT) provides 18 questions to GW
2/1/2018	BRT participates in Office of Pharmaceutical Quality (OPQ)-only teleconferences with GW to ask additional questions pertaining to the quality control of the botanical raw material
2/20/2018	Mid-cycle communication; agency indicates a REMS was not likely to be required
2/20/2018	BRT provides six additional questions to GW
2/22/2018	BRT participates in OPQ-only teleconferences with GW to ask additional questions pertaining to the quality control of the botanical raw material
2/23/2018	GW submits additional information on the management of transaminase elevations during the studies
3/9/2018	GW submits request for reconsideration for Epidiolex proprietary name
3/18/2018	GW submits amendment to the request for reconsideration of proprietary name
3/21/2018	ONDP management determines cannabidiol is not a botanical drug substance and can be best described as a highly-purified drug substance
4/3/2018	Late-cycle communication; agency indicates a REMS was not likely to be required
4/19/2018	DMEPA communicates to the DNP that proprietary name Epidiolex is acceptable
4/19/2018	Peripheral and Central Nervous System Drugs Advisory Committee votes 13-0 in favor of risk/benefit profile
6/25/2018	NDA approved for the treatment of seizures associated with DS and LGS in patients ages 2 and older
6/27/2018	PDUFA Date