What Is XEN1101?
XEN1101 is an investigational drug being studied as an oral capsule. It is currently under investigation for several neurological and mood-related conditions. As of the latest data, a total of 8 clinical trials have been conducted or are ongoing for XEN1101, with 3 trials currently recruiting participants and 4 trials completed. These studies have collectively enrolled 2,323 participants. The first clinical trial for XEN1101 began on 2019-01-08, and the most recent trial started on 2023-02-08.
The primary sponsor for XEN1101 research is Xenon Pharmaceuticals Inc., an industry sponsor, which has sponsored 7 out of 8 trials. One trial has been sponsored by James Murrough. XEN1101 is being explored for its potential effects in conditions such as focal epilepsy, major depressive disorder, and various types of seizures.
Uses and Conditions Under Study
XEN1101 is currently being investigated for its potential to treat several conditions, primarily focusing on neurological disorders involving seizures, as well as a mood disorder.
- Epilepsy and Seizure Disorders: XEN1101 is extensively studied for its role in seizure management. This includes investigations into Focal Epilepsy (2 trials) and Focal Onset Seizures (2 trials), which are characterized by seizures originating in one area of the brain. The drug is also being studied for Primary Generalized Tonic-Clonic Seizures (1 trial) and general Tonic-Clonic Seizures (1 trial), which involve both sides of the brain and typically present with muscle stiffening and jerking. These studies aim to determine if XEN1101 can help reduce the frequency or severity of these types of seizures.
- Major Depressive Disorder: XEN1101 is also under investigation for its potential therapeutic effects in Major Depressive Disorder (2 trials). This condition is characterized by persistent feelings of sadness and loss of interest, impacting daily life. Research in this area seeks to understand if XEN1101 can alleviate symptoms associated with depression.
- Healthy Volunteers: In addition to specific conditions, XEN1101 has been studied in Healthy Volunteers (1 trial). These studies are crucial for understanding how the drug is absorbed, distributed, metabolized, and excreted in the body, as well as for assessing its safety and tolerability in individuals without the target conditions.
Dosing
XEN1101 has been studied in various oral capsule forms and strengths during its clinical development. The drug is administered as an oral capsule, with trial descriptions mentioning "XEN1101 Capsules" and "XEN1101 oral capsule."
Different strengths and daily dosages of XEN1101 have been investigated across the clinical trials. These include:
- 10 mg XEN1101 capsules
- 15 mg/day XEN1101
- 20 mg XEN1101 capsules
- 25 mg/day XEN1101
- Combinations such as 15 or 25 mg/day XEN1101
Some studies have also utilized a radiolabeled version, (14C)-XEN1101, for specific pharmacokinetic assessments. The exact frequency of administration (e.g., once daily, twice daily) and whether it should be taken with or without food are details that would be specified within individual trial protocols, but are not broadly detailed in the available drug descriptions.
Side Effects
In a clinical trial involving 211 patients taking XEN1101 for focal epilepsy, the most common side effect was dizziness. 24.6% of patients taking XEN1101 experienced dizziness, compared to 7.0% on placebo.
Other common side effects reported by patients taking XEN1101, compared to placebo, included:
- Somnolence (sleepiness): 15.6% on XEN1101 vs 7.0% on placebo.
- Fatigue: 10.9% on XEN1101 vs 5.3% on placebo.
- Headache: 10.0% on XEN1101 vs 7.9% on placebo.
- Balance disorder: 9.0% on XEN1101 vs 1.8% on placebo.
- Tremor: 8.5% on XEN1101 vs 1.8% on placebo.
- Gait disturbance (problems with walking): 5.7% on XEN1101 vs 0.9% on placebo.
- Aphasia (difficulty with language): 4.7% on XEN1101 vs 0.9% on placebo.
Less common side effects, also reported more frequently with XEN1101 than with placebo, included confusional state (4.7% vs 0.9%), memory impairment (4.3% vs 0.9%), ataxia (problems with coordination, 4.3% vs 0.9%), and dysarthria (slurred speech, 4.3% vs 0.0%).
Clinical Trial Results
XEN1101 was evaluated in a clinical study (NCT03796962) as an add-on therapy for adults with focal epilepsy.
Reduction in Seizure Frequency
One key measure of effectiveness was the median percent change in focal seizure frequency. Patients taking XEN1101 experienced a greater reduction in seizures compared to those on placebo:
- Patients taking 10 mg XEN1101 had a median reduction of 33.2% in focal seizure frequency.
- Patients taking 20 mg XEN1101 had a median reduction of 46.4% in focal seizure frequency.
- Patients taking 25 mg XEN1101 had a median reduction of 52.8% in focal seizure frequency.
- In comparison, patients taking placebo had a median reduction of 18.2% in focal seizure frequency.
The study also looked at the percentage of patients who achieved at least a 50% reduction in focal seizure frequency. This was observed in:
- 13 participants taking 10 mg XEN1101.
- 22 participants taking 20 mg XEN1101.
- 61 participants taking 25 mg XEN1101.
- In the placebo group, 17 participants achieved a 50% reduction in focal seizure frequency.
When observing the percent change in focal seizure frequency over time, patients on XEN1101 generally showed sustained or improved reductions. For example, patients on 25 mg XEN1101 experienced reductions ranging from 55.3% to 64.7%, while those on 20 mg XEN1101 saw reductions from 40.0% to 52.2%. Patients on 10 mg XEN1101 experienced reductions from 30.3% to 40.1%. Placebo reductions ranged from 14.9% to 21.8%.
Currently Recruiting Trials
XEN1101 is currently being investigated in several Phase 3 clinical trials for individuals experiencing seizures. These studies aim to gather more information about XEN1101's effectiveness, safety, and how well it is tolerated as a potential new treatment option.
One ongoing study, "A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE3)," is a randomized, double-blind, placebo-controlled trial. This study, identified as NCT05716100, is evaluating XEN1101 as an add-on therapy for focal-onset seizures. Participants will receive either XEN1101 at a daily dose of 25 mg or 15 mg, or a placebo. The trial is sponsored by Xenon Pharmaceuticals Inc. and plans to enroll approximately 360 individuals.
Another important trial, NCT05718817, is an open-label study titled "An Open-label Study of XEN1101 in Epilepsy." This Phase 3 study is designed to assess the long-term safety, tolerability, pharmacokinetics, and efficacy of XEN1101 for up to 6 years. It includes subjects with focal onset seizures or primary generalized tonic-clonic seizures, with daily dosages of XEN1101 at 15 mg or 25 mg. Xenon Pharmaceuticals Inc. is sponsoring this study, which aims to recruit around 880 participants.
Finally, the study NCT05667142, "A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures," is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial. This study is evaluating XEN1101 as an adjunctive treatment for primary generalized tonic-clonic seizures. Participants will receive XEN1101 at either 25 mg or 15 mg per day, or a placebo. Xenon Pharmaceuticals Inc. is the sponsor, and the trial is targeting an enrollment of 160 individuals.
Where to Participate
Clinical trials for XEN1101 are actively recruiting across a wide geographic area, making participation accessible to many individuals. These studies are being conducted at 101 sites across 66 cities in 32 states. This broad reach helps ensure diverse representation in the research.
Some of the locations with multiple participating sites include:
- Lexington, Kentucky (4 sites)
- Columbus, Ohio (4 sites)
- Jacksonville, Florida (3 sites)
- Orange, California (3 sites)
- Hackensack, New Jersey (3 sites)
- Cleveland, Ohio (3 sites)
- Durham, North Carolina (3 sites)
- Charlotte, North Carolina (3 sites)
- Salt Lake City, Utah (3 sites)
- Baltimore, Maryland (3 sites)
To be eligible for these XEN1101 trials, participants must be between 12 and 18 years of age. All genders are welcome to participate, and the studies are specifically designed for individuals with the targeted medical conditions, not healthy volunteers. Children are eligible to join these trials.
Development Timeline
The journey of XEN1101 began with its first clinical trial starting on January 8, 2019. Since then, the development program has expanded significantly, with the latest trial commencing on February 8, 2023. In total, 8 clinical trials have been conducted or are ongoing for XEN1101, involving a cumulative enrollment of 2,323 participants.
Xenon Pharmaceuticals Inc. has been the primary driving force behind XEN1101's development, sponsoring 7 of these trials. The program has progressed through various stages, including 1 Phase 1 trial, 3 Phase 2 trials, and currently 4 Phase 3 trials, indicating a mature stage of clinical investigation.
Initially, XEN1101 was explored for conditions such as IBS-C and hyperphosphatemia. Over time, the research pipeline broadened to include Major Depressive Disorder and studies in Healthy Volunteers. More recently, the focus has shifted and expanded significantly into neurological conditions, specifically Primary Generalized Tonic-Clonic Seizures and Tonic-Clonic Seizures, reflecting a strategic evolution in the drug's therapeutic targets.