2018 saw many progresses in the Dravet syndrome drug pipeline, including major milestones such as the approval and launch of Epidiolex in the US, the completion of a second very successful pivotal trial with fenfluramine, the initiation of clinical trials in Dravet syndrome by Ovid and Takeda and the appearance out of the blue of Stoke Therapeutics, with an antisense approach for restoring Nav1.1 expression in Dravet syndrome.
Some of these news were already anticipated by the companies at the beginning of the year (reviewed here), so we knew when to expect them. But other took us by surprise, mainly around the programs that were less advanced at the beginning of the year.
Keeping that in mind, here is what we can expect in 2019 from the Dravet syndrome programs from GW Pharmaceuticals, Zogenix, Ovid Therapeutics and Takeda, PTC Pharma and NYU, OPKO Health, and Stoke Therapeutics, based on what these companies have communicated.
Epidiolex (cannabidiol) – GW Pharmaceuticals
The decision from the EMA to approve or not Epidiolex for the treatment of Dravet and Lennox-Gastaut syndrome is due within the first quarter of 2019, and if the decision is positive, GW hopes to start the first national launches of Epidiolex starting as early as Q2 2019.
Fintepla (fenfluramine) – Zogenix
Zogenix also expected to deliver good news during the first quarter of 2019, when it planned to complete the submissions of the marketing authorizations for the two largest markets (called NDA in the US and MAA in Europe). This was one of the first news that we had in 2019, since the successful double-submission was announced at the beginning of February.
We should have the news about the FDA decision on Fintepla in Q3 2019, followed by a launch in the US market before the end of the year. For the approval and launch in Europe we will have to wait until 2020.
Translarna (ataluren) – PTC Therapeutics / NYU
Last year we anticipated to get the results of the Phase 2 clinical trial with ataluren in children with Dravet syndrome caused by nonsense mutations during the second quarter of 2018. However the clinical trial has not yet been completed (according to clinicaltrials.gov it is active but not recruiting and is still ongoing in the last PTC pipeline review). In the absence of any public estimates on trial completion, all we can estimate is that if the trial has completed enrollment, and based on the trial protocol duration, we might expect to hear news by the end of Q2 2019.
TAK-935 (OV935) – Ovid Therapeutics / Takeda
Even before completing the Phase2a basket trial in adult patients with different developmental and epileptic encephalopathies, Ovid and Takeda announced the initiation of a Phase 2 clinical trial in pediatric patients with Dravet syndrome and Lennox-Gastaut syndrome. The trial, called ELEKTRA, is currently recruiting and based on the company last estimates it will continue to enroll during 2019. This means that we might or might not get the news of the next milestone for this program for Dravet syndrome during 2019, which would be the completion of trial enrollment.
OPK88001 – OPKO Health
Over the years OPKO has provided very limited information on their program targeting Dravet syndrome with an antisense therapy. 2017 materials had indicated that the therapy, OPK88001, would be ready to start clinical trials in late 2017, which was later to moved to be planned to start somewhere during the first half of 2018. The latest corporate update, from June of 2018, still lists the program as active and indicates the Phase 2 trial will start during the second half of 2018. There were no news about the trial initiation and there are no more news about this program. The program is still listed as active in the last company presentation of September 2018 but no timelines were provided. We are therefore not able to predict if we will hear any news from this program during 2019.
Antisense Oligonucleotide - Stoke Therapeutics
One of the big news of 2018 was Stoke Therapeuticscoming out of stealth mode with an antisense oligonucleotide approach to restoring expression of the protein missing in Dravet syndrome, and plans to bring the antisense therapy into the clinic by 2020. Although the company has not communicated any expected release of news to take place during 2019, it is predictable that during 2019 Stoke will announce the clinical trial plans, and communicate/publish more complete preclinical proof-of-concept data that supports their clinical trial plans.
During the American Epilepsy Society meeting in December of 2018, the company Encoded Genomics, still in stealth mode, appeared as a new company developing a gene therapy approach for the treatment of Dravet syndrome. The company sponsored the Dravet Syndrome Roundtable and were open about the fact that they are developing such therapeutic approach, although no more details were given. If Encoded or any other new company confirms that they are working on a gene therapy for Dravet syndrome, and releases some news during 2019, it will solidify the transition of Dravet syndrome from a disease that we manage with symptomatic anticonvulsant medications to a disease that we can start targeting with a variety of gene therapy approaches.
2019 will be the year when we might have the European launch of Epidiolex, the US approval and launch of Fintepla, an ongoing clinical trial with TAK-935, hopefully some news about the ability of Translarna to improve Dravet syndrome by rescuing some of the nonsense mutations, and a year to prepare for the clinical trials that starting in 2020 will dominate the field: gene therapy approaches for Dravet syndrome that will treat more than just seizures.
Ana Mingorance, PhD
 GW Pharma company presentation January 2019
 Zogenix investor update December 2018 and press release 6 February 2019
 ClinicalTrials.gov information for NCT02758626
 Ovid Therapeutics Press Release 4 January 2019
 OPKO Health company presentation September 2018
 Stoke Therapeutics press release December 2018
Announcements within the same quarter ordered by drug name (alphabetic).