Amit Rakhit, MD, MBAAmit Rakhit, MD, MBA
Ovid Therapeutics has announced initial data from the phase 2 ARCADE study of soticlestat (also known as TAK-935), stating the drug showed a significant reduction in seizure frequency in patients with CDKL5 deficiency disorder (CDD) and Dup15q syndrome (Dup15q).

Due to the study consisting of only 11 patients—5 with CDD and 6 with Dup15q syndrome—data was limited but highlighted specific patients’ achievements. Overall, soticlestat was found to be well tolerated, with the majority of the cohort showing a reduction in seizures.  

“This initial data set from the open-label ARCADE study includes the first 11 patients enrolled. This data cut was designed to confirm the safety profile of soticlestat in these patient populations and assess any signals of efficacy,” Amit Rakhit, MD, MBA, president and chief medical officer, Ovid Therapeutics, said in a statement. “These initial data suggest that soticlestat continues to be safe and well tolerated and appears to reduce seizure frequency in a majority of the individual patients.”

ARCADE is a phase 2, ongoing, multicenter, open-label, pilot study (NCT03694275) of soticlestat in patients ages 2 to 55 with refractory epileptic seizures associated with CDD or Dup15q. Started in September 2018, the study is investigating the frequency of motor seizures in 30 patients who receive soticlestat twice daily, and is comprised of 2 periods.
 
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First, patients will undergo a 4- to 6-week screening/baseline period and then a treatment period. The treatment period aims to test dose optimization and maintenance, lasts 20 weeks and is followed up by a 2-week taper and 2-week safety follow-up period. Upon completion, patients may enroll in the open-label extension study, under a separate protocol.  

Researchers used percent change from baseline in motor seizure frequency during the 12-week maintenance period as the primary outcome measure. Other secondary outcomes included the percentage of participants considered as treatment responders, change from baseline in Clinician’s Global Impression of Severity and Change (CGI-S/C) responses, and correlation of plasma 24S-hydroxycholesterol (24HC) levels and change in motor seizures.

Among the 5 patients with CDD included in the data sample, the median age was 4 years and baseline overall seizure frequency ranged from 10 to 326 per 28 days. Those with Dup15q had a median age of 13.5 years and baseline overall frequency range of 35 to 630 per 28 days. Most of the patients were concomitantly treated with 2 anti-seizure medications (ASMs), with the most common being topiramate, clobazam, felbamate, rufinamide and valproate.

Researchers noted a variety of different seizure types including motor (tonic and clonic), cluster, and epileptic spasms in the CDD group. Data showed a range of different reactions towards soticlestat with all but 1 patient experiencing a meaningful improvement in any type of seizure reduction.

More specifically, 1 patient showed 61% fewer motor seizures during maintenance phase (75% reduction during the full treatment period) with 2 consecutive seizure-free 28-day intervals. Additionally, motor seizure-free days increased by 37% and 38% in 2 of the 3 patients that completed the full treatment period at the time of the data cut.

Patients in the Dup15q cohort experienced seizure types including motor (tonic and clonic), myoclonic and absence seizures. Of the 6 patients observed, 3 showed a 60%, 66%, and 100% reduction of myclonic seizures over the maintenance period while 2 patients showed 78% and 74% reduction of absence seizures during the same period. Additionally, 1 patient with pure motor seizures showed seizure frequency reduce by 90%.

ENDYMION, the open-label extension of ARCADE, aims to assess safety and tolerability of soticlestat over 4 years in patients with rare epilepsies, as well as look at the seizure frequency over time.

A total of 6 patients that completed ARCADE (CDD: n = 2; Dup15q: n = 4), researchers noted similar seizure reduction that supports the potential of soticlestat. All 4 patients with Dup15q showed reduction in overall seizures, while 1 patient with CDD had a reduction in overall seizures of 56% during their most recent 12-week interval.

When evaluating safety, soticlestat was generally well tolerated and demonstrated a safe profile. Constipation (n = 3; 27%), fatigue (n = 2; 18%), nasopharyngitis (n = 2; 18%) and seizure (n = 2; 18%) were among the most common adverse events (AEs). Notably, there were no AE-related withdrawals, as well as no serious AEs or deaths reported.

“These early results are encouraging and are supportive of continuation of the ARCADE study. We are also encouraged that all ARCADE patients that have completed the study to date have opted to roll over into the ENDYMION open-label extension study,” Rakhit added. “We will work closely to evaluate the full data from the ARCADE study, expected in the first quarter of 2021.”
REFERENCE
Ovid Therapeutics announces initial data with soticlestat in CDKL5 deficiency disorder and Dup15q syndrome [news release]. New York, NY: Ovid Therapeutics; Published March 30, 2020. Accessed March 31, 2020. finance.yahoo.com/news/ovid-therapeutics-announces-initial-data-120010372.html