With 2018 now behind us, it is time to review how well companies working on Dravet syndrome delivered based on the timelines that they had announced at the beginning of the year. This was the summary figure that I published a year ago outlining what to expect in 2018:
So how did it go?
While it is hard to predict exactly when many milestones are going to happen, in particular those still over half a year away or more, the class of 2018 did quite well overall, and many of the news that we were expecting took place on schedule – with some exceptions.
Ataluren – Phase 2 clinical trial
Ataluren (Translarna, by PTC Therapeutics) is being tested in a double-blind placebo controlled Phase 2 trial in patients with Dravet syndrome and CDKL5 Deficiency Disorder due to non-sense mutations. Although early last year the trial was expected to have results by Q2 of 2018, the trial is not yet completed and so the results have not been communicated. This is an investigator-indigitated trial involving only one clinical site so any delays in recruitment in that site cannot be buffered by recruitment elsewhere and has therefore a large impact on the trial timelines.
Epidiolex – FDA approval and US launch
2018 promised to be a very exciting year for GW Pharma (Greenwich Pharmaceuticals in the US) and it did not disappoint. Every expected milestone came successfully and on time.
The first milestone was the FDA marketing authorization that came as planned in Q2 2018, following a very successful FDA advisory committee meeting some months before. After approval, the DEA rescheduled Epidiolex (cannabidiol) in Q3, enabling a successful market launch in Q4 (November). Epidiolex is currently available in all 50 states.
GW also expected the announcement of the results of the second pivotal trial in Dravet syndrome to take place during the second half of 2018. The results were announced in November and matched the previous three positive pivotal trials in Dravet syndrome (one) and Lennox-Gastaut syndrome (two).
All in all, a very good year for GW, that expects the European marketing authorization in the first quarter of 2019.
Fintepla – Second pivotal trial data and regulatory filing
Zogenix also had a very good 2018, with the expected timelines being only slightly optimistic. The announcement of the results of the second pivotal trial with Fintepla (fenfluramine) in Dravet syndrome planned for Q2 ended up coming in July, and confirmed the first pivotal trial results showing unprecedented efficacy in this very difficult patient population.
The NDA submission was initiated on schedule in Q4, but is expected to be completed during Q1 of 2019, together with the European MAA, after Zogenix communicated that after pre-NDA discussions with the FDA they had decided to “conduct some additional analyses of our clinical data that could positively impact our product label” which would delay the submission of the final sections of the NDA by just a couple of months.
So, all in all, also a very good year for Zogenix.
OPK88001 – Initiation of first clinical trial
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 are no further news about this program.
But just as the patient community wondered if the therapy from OPKO will ever move into the clinic, Stoke Therapeuticscame out of stealth mode with another antisense oligonucleotide approach to restoring expression of the protein missing in Dravet syndrome. So while the program from OPKO might not have reached the milestones that it expected to reach this year, a strong contender has appeared and has plans to bring the antisense therapy into the clinic by 2020.
OV935 / TAK-935– Results from the basket trial
The last clinical trial news that were expected for 2018 were the results of the Phase1b/2a basket trial with patients with mixed epilepsy syndromes that Ovid Therapeutics and Takeda were running with their molecule. The companies had planned to release the top data of this trial in the second half of the year, and just as we were wrapping up the year the trial results were announced, meeting another successful milestone. The trial had very promising efficacy data in a group of patients that included cases of Dravet syndrome, Lennox-Gastaut syndrome and other rare epilepsies.
Even before the completion of the pilot trial, Ovid and Takeda decided to move forward with additional clinical trials with OV935 (TAK-935) in four rare epilepsies, announcing in September of 2018 the initiation of a placebo-controlled Phase 2 clinical trial in Dravet syndrome and Lennox-Gastaut syndrome, and a smaller open-label Phase 2 trial in CDKL5 Deficiency Disorder and Dup15q syndrome.
So for Ovid and Takeda, 2018 delivered even more for Dravet syndrome 8and for OV935) than they had envisioned at the beginning of the year.
In the next article I will review the news that we can expect in 2019 from those programs that are in clinical trials for Dravet syndrome.
Ana Mingorance PhD