Exondys 51 Clinical Development Timeline

Chronicle of the development and FDA review of Sarepta's eteplirsen for Duchenne muscular dystrophy.

Date	Action
IND Chronology (#077429)
10/23/2007	Orphan drug designation granted
11/27/2007	Fast Track designation granted
6/14/2011	End-of-Phase I meeting
7/12/2012	Receipt of change of sponsor from AVI Biopharma to Sarepta Therapeutics
3/13/2013	End-of-Phase II meeting to discuss suitability for NDA filing under Subpart H
7/23/2013	Type C guidance meeting held as a continuation of discussion from 3/13/2013
10/17/2013	End-of-Phase II meeting on chemistry, manufacturing and controls (CMC) issues
11/8/2013	Guidance meeting on evidence supporting eteplirsen's efficacy and design of future studies
11/15/2013	Guidance meeting
12/19/2013	Guidance meeting
2/7/2014	Teleconference to discuss dystrophin data
3/19/2014	Guidance meeting
4/15/2014	FDA advice letter on agency's view of the currently available eteplirsen clinical and biomarker data and proposed strategy for NDA submission
4/23/2014	Teleconference to discuss logistics for roundtable discussion with pathologists at Nationwide Children's Hospital to clarify quantification methodology for dystrophin data; FDA and Sarepta agree that agency representatives will visit Nationwide and view biopsy slides
5/29/2014-5/30/2014	FDA site visit to Nationwide Children's Hospital
7/29/2014	Advice letter requesting independent, blinded review by three pathologists of raw immunohistochemistry images from Study 201/202
9/3/2014	Pre-NDA meeting on CMC issues
9/18/2014	Type B meeting on strategy and content of an NDA submission
10/15/2014	Teleconference on sponsor's proposed methodology for rescoring dystrophin images from Study 201/202
5/19/2015	Type C guidance meeting on content of NDA
NDA Chronology (#206488)
6/26/2015	NDA submitted
8/20/2015	Priority review granted
10/3/2015	Proposed proprietary name Exondys 51 deemed conditionally acceptable
10/22/2015	Mid-cycle communication
1/8/2016	Sarepta submits major amendment with additional information on historical control group
1/11/2016	Late-cycle meeting
1/15/2016	FDA releases background briefing documents for advisory committee meeting
1/22/2016	Originally scheduled advisory committee meeting (postponed due to a snowstorm)
2/5/2016	FDA extends user fee goal date by three months
2/26/2016	Original PDUFA goal date
4/25/2016	Advisory committee meeting
5/4/2016	During an internal briefing with the review team, Center for Drug Evaluation and Research Director Janet Woodcock makes clear her intention to approve eteplirsen
5/24/2016	FDA informs Sarepta it will miss re-set PDUFA goal date
5/26/2016	Extended PDUFA goal date passes
5/31/2016	Woodcock meets with review team members to discuss their reviews and her initial draft decisional memorandum based primarily on the data from Study 201/202
6/1/2016	FDA requests teleconference with Sarepta to discuss submission of immunohistochemistry and Western blot analyses of biopsies from ongoing Study 301; Sarepta emails Woodcock and Deputy Director of Science Operations Richard Moscicki requesting urgent telephone call to discuss request for additional dystrophin data and says it would take several months to analyze samples from Study 301
6/2/2016	Teleconference on plans for dystrophin analysis from Study 301; in follow-up email to Woodcock and Moscicki, Sarepta requests agency confirm that accelerated approval will be granted by end of June when an increase in dystrophin is demonstrated in the Study 301 data, and says any delay will significantly impact company's ability to continue ongoing eteplirsen studies
6/3/2016	General advice letter signed by Woodcock regarding plans for FDA monitoring of Western blot procedures for Study 301 states that agency expects to be able to grant accelerated approval within four business days of receiving the data if a meaningful increase in dystrophin is demonstrated
6/6/2016	Teleconference to discuss dystrophin protocols
6/20/2014-6/24/2016	FDA observation of Western blot analytical procedures for Study 301
6/27/2016	Sarepta submits dystrophin data from Study 301
7/6/2016	Woodcock meets with review team
7/14/2016	Woodcock finalizes decisional memo to grant accelerated approval
7/16/2016	Office of Drug Evaluation I Director Ellis Unger finalizes decisional memo supporting a complete response letter
7/18/2016	Unger appeals to Office of Scientific Integrity
8/8/2016	Scientific Dispute Process Review Board memorandum on Unger's appeal
9/13/2015	FDA Commissioner Robert Califf internally circulates draft decisional memo
9/16/2016	Commissioner's final decisional memo
9/19/2016	Exondys 51 receives accelerated approval