Phase 2 ELEKTRA Study of Soticlestat (TAK-935/OV935) Meets Primary Endpoint Reducing Seizure Frequency in Children with Dravet Syndrome or Lennox-Gastaut Syndrome

Osaka, Japan & New York, United States: 

− Primary endpoint achieved, demonstrating a statistically significant reduction of seizures from baseline compared to placebo (p=0.0007) in the combined Dravet syndrome and Lennox-Gastaut syndrome study population

− Statistically significant reduction in seizure frequency from baseline in Dravet syndrome cohort compared to placebo (p=0.0007); based on strong efficacy results, Takeda and Ovid plan to initiate a Phase 3 registrational program of soticlestat in Dravet syndrome

− Data from Lennox-Gastaut syndrome cohort demonstrated numeric reductions in seizure frequency compared to placebo but did not achieve statistical significance (p=0.1279); data analysis ongoing for the Lennox-Gastaut syndrome patients

− Soticlestat was well-tolerated and demonstrated a safety profile consistent with the findings of previous studies with no new safety signals identified

− Ovid to host conference call and webcast today at 8:00 a.m. EDT

Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) and Ovid Therapeutics Inc. (NASDAQ: OVID) (“Ovid”), a biopharmaceutical company committed to developing medicines that transform the lives of people with rare neurological diseases, today announced positive topline results from the randomized Phase 2 ELEKTRA study of soticlestat in children with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS). Soticlestat is a potent, highly selective, oral, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H). It is being investigated by Ovid and Takeda for the treatment of rare developmental and epileptic encephalopathies (DEEs), a group of highly refractory epilepsy syndromes including DS and LGS.

The ELEKTRA study achieved its primary endpoint with high statistical significance, demonstrating a 27.8% median reduction from baseline in convulsive seizure (DS) and drop seizure (LGS) frequency compared to a 3.1% median increase in patients taking placebo during the 12-week maintenance period (median placebo-adjusted reduction=30.5%; p=0.0007, based on the efficacy analysis set of 120 patients with seizure data in the maintenance period). In addition, DS and LGS patients treated with soticlestat demonstrated a 29.8% median reduction in convulsive seizure (DS) and drop seizure (LGS) frequency compared to 0.0% change in median seizure frequency in patients taking placebo during the full 20-week treatment period (titration plus maintenance) of the ELEKTRA study (placebo-adjusted reduction=25.1%; p=0.0024).

In the ELEKTRA DS cohort (n=51), patients treated with soticlestat demonstrated a 33.8% median reduction in convulsive seizure frequency compared to a 7.0% median increase in patients taking placebo during the full 20-week treatment period of the study (median placebo-adjusted reduction in seizure frequency is 46.0%; p=0.0007). Based on these data, the companies plan to meet with regulatory authorities to discuss initiation of a Phase 3 registrational program for soticlestat in patients with DS.

In the ELEKTRA LGS cohort (n=88), patients treated with soticlestat demonstrated a 20.6% median reduction in drop seizure frequency compared to a 6.0.% median reduction in patients taking placebo during the full 20-week treatment period of the study (median placebo-adjusted reduction in seizure frequency is 14.8%; p=0.1279). Additional analyses are being conducted to better understand the potential next steps for the development of soticlestat in this highly heterogenous patient population.

Soticlestat was generally well-tolerated in the ELEKTRA study and demonstrated a safety profile consistent with those of previous studies, with no new safety signals identified. All patients who completed the ELEKTRA study elected to enroll into the ENDYMION open-label extension study and findings from ENDYMION are also reported today.

“We are extremely encouraged by these results, which show a clear statistically significant reduction of seizures in Dravet syndrome patients treated with soticlestat, as well as a trend for seizure reduction in Lennox-Gastaut patients,” said Amit Rakhit, M.D., MBA, President and Chief Medical Officer of Ovid. “We look forward to continuing our collaboration with Takeda to initiate a Phase 3 registrational program for soticlestat in patients with DS, while continuing to analyze the data from patients with LGS in the ELEKTRA and ENDYMION studies to define potential next steps. We also expect to report data from the open-label Phase 2 ARCADE study with soticlestat in patients with CDKL5 deficiency disorder and Dup15q syndrome, two other types of highly-refractory DEEs, later this quarter.”

“It is exciting to see these positive results and to advance soticlestat into late stage clinical development — initially for the potential treatment of children with Dravet syndrome who need more options to manage treatment-resistant seizures,” said Sarah Sheikh, M.D., M.Sc., MRCP, Head, Neuroscience Therapeutic Area Unit at Takeda. “Soticlestat and its novel mechanism of action were discovered at Takeda and we are enthusiastic about continuing to advance the science and clinical programs as one aligned team, in strong partnership with Ovid Therapeutics.”

“Children with developmental epileptic encephalopathies like DS and LGS need more options to manage their treatment-resistant seizures,” said Dr. Cecil Hahn, M.D., MPH, a Child Neurologist at The Hospital for Sick Children and Associate Professor of Pediatrics at the University of Toronto. “The results of the ELEKTRA study are very promising, particularly for children with DS and represent a clinically significant reduction in seizure burden. Moreover, soticlestat was well-tolerated in this study.”

 

Phase 2 ELEKTRA Study Design and Patient Baseline Demographics

ELEKTRA was an international, multi-center, randomized, double-blind, placebo-controlled study designed to evaluate treatment with soticlestat in pediatric patients, aged 2 to 17 years, with highly refractory epileptic seizures associated with DS (convulsive seizures) or LGS (drop seizures). The study consisted of a four- to six-week screening period to establish baseline seizure frequency, followed by a 20-week double-blind treatment period, including an 8-week dose optimization period and a 12-week maintenance period. During the 8-week dose optimization period, patients were titrated from 100mg twice daily (BID), to 200mg BID to 300mg BID (mg/kg dosing for <60 kg) of orally administered soticlestat.

A total of 141 patients were enrolled in ELEKTRA and 126 completed the study. A modified intent-to-treat (mITT) analysis of 139 patients was performed to evaluate the efficacy endpoints, which includes any patient who enrolled in the study and received at least one dose of study drug. Patients in the study were allowed to be on one to four concomitant anti-epileptic drugs (AEDs), with the majority of patients concomitantly treated with at least three AEDs. The most common AEDs taken by the patients were valproate, clobazam, levetiracetam and topiramate.

Phase 2 ELEKTRA Topline Efficacy Results

The study achieved its primary endpoint, demonstrating a 27.8% median reduction from baseline in convulsive seizure (DS) and drop seizure (LGS) frequency compared to a 3.1% median increase in patients on placebo during the 12-week maintenance period (median placebo-adjusted reduction=30.5%; p=0.0007, based on the efficacy analysis set of 120 patients with seizure data in the maintenance period). During the full 20-week treatment period of the mITT DS patient population, the median percent change from baseline was a 33.8% decrease in seizure frequency compared to a 7.0% increase in seizure frequency for patients receiving placebo (median placebo-adjusted reduction=46.0%; p=0.0007). During the full treatment period of the mITT LGS patient population, the median percent change from baseline was a 20.6% decrease in seizure frequency compared to a 6.0% decrease in patients receiving placebo (median placebo-adjusted reduction=14.8%; p=0.1279).

Phase 2 ELEKTRA Topline Safety Results

Soticlestat was well tolerated in this study. These findings were consistent with previous studies and no new safety signals were identified. The incidence of treatment emergent adverse events was similar in both the treatment and placebo groups with 57 (80.3%) of soticlestat patients experiencing at least one treatment emergent adverse event compared to 52 (74.3%) placebo patients. The most frequent treatment emergent adverse events reported in soticlestat-treated patients with ≥5% difference from placebo were lethargy and constipation. The incidence of serious adverse events was similar in both soticlestat and placebo groups, with 11 (15.5%) in soticlestat experiencing at least one treatment emergent serious adverse event compared to 13 (18.6%) in placebo. There were no deaths reported.

NDYMION Open-Label Extension Study Update

All patients who completed the ELEKTRA trial elected to roll over into the ENDYMION open-label extension study. The primary objective of ENDYMION is to assess the long-term safety and tolerability of soticlestat over four years of treatment in patients with rare epilepsies and, secondarily, to evaluate the effect of soticlestat on seizure frequency over time.

Data from the ELEKTRA patients who have rolled over into the ENDYMION study are supportive of results in the core study. The data indicate maintenance of effect over 6 months in those patients originally randomized to soticlestat, and similarly reduced seizure frequency as compared to baseline in those patients previously assigned to the placebo arm. No new safety signals were identified in ENDYMION.

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