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New epilepsy drugs: what is in the pipeline?

According to the World Health Organization (WHO), around 50 million people worldwide have epilepsy, making it one of the most common neurological diseases globally. Although treatments are already available for the disease – which include narrow-spectrum anti-epileptic drugs (AEDs) to treat specific types of seizures, and broad-spectrum AEDs to treat generalized seizures – it is estimated that approximately 30% to 40% of people have drug-resistant epilepsy, where they do not respond to current AEDs. This underscores the need for new epilepsy drugs to reach the market.

But what is in the pipeline? In this article, we go through some of the latest announcements regarding new epilepsy drugs currently in development.

Table of contents

    New epilepsy drug reduces the frequency of seizures by more than 50%

    Focal seizures are the most common type of seizure seen in epilepsy, occurring when the nerve cells in a particular region of the brain send out a sudden, excessive burst of electrical signals. Not only does this result in seizures, but also in abnormal behavior, periods of lost awareness, and mood changes.

    A phase 2b trial was recently conducted in patients with focal epilepsy by researchers at NYU Grossman School of Medicine. The study showed that patients who added an investigational epilepsy drug, called XEN1101, to their current antiseizure treatments saw a 33% to 53% drop in monthly seizures, depending on their dose. By contrast, those given a placebo had on average 18% fewer seizures during the treatment phase of the trial, which lasted eight weeks. Most patients then volunteered to extend the trial, with about 18% of those treated with XEN1101 remaining entirely seizure-free after six months, and about 11% having no seizures after a year or longer.

    XEN1101 is part of a class of chemicals called potassium-channel openers, which avert seizures by boosting the flow of potassium out of nerves, stopping them from firing. 

    Jacqueline A. French, the study’s lead author, said in NYU Langone Health’s press release, that one of the major benefits of this new drug is that it takes more than a week to break down, so levels in the brain remain consistent over time. This steadiness allows the treatment to be started at full strength and helps to avoid dramatic spikes that worsen side effects and dips that allow seizures to return. 

    The sponsor of the phase 2b trial was Xenon Pharmaceuticals, a biotech company that develops therapies for neurological disorders. Xenon is currently developing XEN1101 and has initiated its phase 3 development program for the drug, which includes two identical phase 3 clinical trials called X-TOLE2 and X-TOLE3. 

    The team at NYU Grossman School of Medicine is also looking to explore the use of XEN1101 for other types of seizures, including generalized seizures. 

    Longboard Pharmaceuticals’ LP352 reduces motor seizures 

    On January 2, Longboard Pharmaceuticals announced positive topline data from its phase 1b/2a study of its epilepsy drug LP352 for seizures associated with a broad range of developmental and epileptic encephalopathies (DEEs) – a term that refers to when cognitive functions are influenced by both seizure and interictal epileptiform activity and the neurobiological process behind the epilepsy. 

    The PACIFIC study involved 52 participants aged 12 to 65 years old and was designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of LP352 at doses of 6mg, 9mg, and 12mg three times daily versus placebo. 

    The primary endpoint of the trial was a median change in countable motor seizure frequency, with patients treated with the new epilepsy drug showing a 53.3% decrease, compared to a 20.8% decrease in the placebo group. Furthermore, the drug demonstrated favorable safety and tolerability, with 85.7% of patients tolerating the highest dose. All of the participants who completed the study also opted for an ongoing open-label extension. 

    LP352 is an oral, centrally acting, 5-HT2C superagonist, designed to modulate gamma-aminobutyric acid (GABA) – the primary inhibitory neurotransmitter in the brain – and, as a result, suppress the central hyperexcitability that is characteristic of seizures. It was also designed to be more specific and selective for the 5-HT2C receptor subtype, giving it the potential to reduce seizures in patients with DEEs while overcoming the known or perceived safety limitations of available drugs.

    After Longboard announced the positive data from its phase 1b/2a trial, the biotech’s stock soared by 316%. Longboard is now planning to advance LP352 into a global phase 3 program.

    Cell therapy candidate for drug-resistant epilepsy

    Based in South San Francisco, biotech company Neurona Therapeutics is currently developing an allogeneic cell therapy candidate for the treatment of drug-resistant mesial temporal lobe epilepsy (MTLE), which is a common type of focal epilepsy in adults and primarily affects the internal structures of the temporal lobe, where seizures often begin in a structure called the hippocampus.

    The candidate is called NRTX-1001. It is a regenerative neural cell therapy candidate derived from human pluripotent stem cells. The fully-differentiated neural cells, called interneurons, secrete GABA. Delivered as a one-time dose, the human interneurons are intended to integrate and innervate on-target neural circuits and are designed to durably silence seizure activity in the epileptic region of the brain. 

    NRTX-1001 is currently being tested in a phase 1/2 open-label trial. In December 2023, Neurona said that the first two patients continued to report a greater than 95% reduction from baseline in overall seizure counts more than one year after NRTX-1001 administration. The first patient had a baseline seizure frequency of 32 seizures per month, but after being in the study for 17 months, they reported no focal impaired awareness seizures since the first month post-treatment. Meanwhile, the second patient had a baseline seizure frequency of 14 seizures per month, but after 12 months of being in the trial, they had not reported a focal impaired awareness seizure for six months.

    The Data Safety Monitoring Board (DSMB) overseeing the phase 1/2  trial also cleared continuing enrollment for another five patients who will receive a one-time administration of the higher dose level of NRTX-1001.

    Global epilepsy drug market will continue to grow 

    According to Precedence Research, the global epilepsy drug market size reached $7 billion last year, and is projected to hit around $9.45 billion by 2032, expanding at a compound annual growth rate (CAGR) of 3.40% during the forecast period. 

    This predicted growth rate reinforces the need for new epilepsy drugs. And with a robust pipeline of potential epilepsy drugs in various stages of development, we could see new treatment options be approved soon, bringing hope to the large number of people suffering from epilepsy that does not respond to currently available medications.

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