Which Pharma Companies are Transforming the Drug-Resistant Epilepsy Market Landscape?

In the United States, more than 2.5 million people are living with Epilepsy, out of which approximately 1 million continue to experience seizures despite adequate treatment with antiseizure drugs. Known as Drug-resistant epilepsy (DRE) or refractory epilepsy, it is a form of epilepsy that is defined as a failure of adequate trials of 2 tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapy or in combination) to achieve sustained seizure freedom. It can possibly be a cause of wrong diagnosis, wrong medication, or triggers that can give rise to seizures. Further, lifestyle factors such as sleep-deprivation, and alcohol consumption can also cause uncontrollable seizures. 

A single seizure, however, due to high fever a.k.a febrile seizures or any head injury does not imply that a person has Drug-resistant epilepsy. Hallmark signs of DRE involve persistence of seizures despite adequate doses of two or more appropriate first-line antiepileptic drugs (AEDs).

The signs and symptoms of Drug-resistant epilepsy include temporary confusion, a staring spell, uncontrollable jerking movements of the arms and legs, loss of consciousness or awareness, psychic symptoms, limp or weak muscles, and others. 

The Drug-resistance epilepsy treatment paradigm comprises management strategies that involve three main categories, i.e., pharmacotherapy, surgery, and alternative treatment strategies, including neurostimulation, ketogenic diet, and lifestyle changes. 

Pharmacotherapy consists of the use of antiepileptic drugs that can be classified as Sodium Channel Modulators, Gamma-Aminobutyric Acid (GABA) Receptor Modulator, Calcium Channel Blockers, Receptor Blockers, Combination Therapies, and some in the other categories. Studies demonstrate that patients who fail to respond to two AEDs have only a small chance to manage seizures with any additional administered AED. Phenytoin, Carbamazepine, Oxcarbazepine, Lamotrigine, Topiramate, Lacosamide, Vimpat, and Levetiracetam are the most commonly used AEDs. Besides AEDs, other drugs such as Fycompa, Felbamate, Neurontin (gabapentin), Ezogabine, Primidone, Eslicarbazepine, Clobazam, Stiripentol, Tiagabine, Sabril, and Banzel (rufinamide). Are also prescribed as add-on therapy in the Drug-resistant epilepsy market. 

Patients who fail to respond to Pharmacotherapy opt for Surgery. As a last resort, patients who do not get any benefits from either medications or surgery go for neurostimulation. However, despite the availability of several medications, drugs, the needs of the majority of Drug-resistant epilepsy patients are unmet. Patients continue to experience refractory seizures, and adverse reactions owing to drug interactions. Thus, there is a need for a better understanding of the epileptic syndrome, and anti-epileptogenic (AEG) agents that have the potential to prevent the development of epilepsy and its comorbidities.

To bridge the gap in the Drug-resistant epileptic market, pharmaceutical companies including PTC Therapeutics, Aquestive Therapeutics, Marinus Pharmaceuticals, Neuroelectrics, InSightec and BrainSonix are dynamically operating in the DRE market landscape. The Drug-resistant epilepsy pipeline at present holds potential novel therapies that can transform the market landscape in the coming next decade. The pipeline possesses few potential drugs in late- and mid-stage developments that are expected to enter the Drug-resistant epilepsy market in the near future like Vatiquinone (PTC Therapeutics), Libervant (Aquestive Therapeutics), and Ganaxolone (Marinus Pharmaceuticals).

Aquestive Therapeutics is running trials to test Libervant as an alternative to device-dependent rescue therapies currently available to patients with refractory epilepsy. Marinus Pharmaceuticals is investigating Ganaxolone, a synthetic analog of allopregnanolone, an endogenous neurosteroid produced in the central nervous system that modulates the brain neurotransmitter GABA. Ganaxolone has received Rare Pediatric Disease Designation from the US FDA for CDKL5 Deficiency Disorder (CDD), Orphan Drug Designation from the US FDA for Refractory status epilepticus (RSE), CDD, and PCDH19-RE and Orphan Drug Designation from the EMA for CDD. 

Similarly, PTC Therapeutics has initiated a registration-directed Phase II/III placebo-controlled trial of Vatiquinone in children with mitochondrial disease and associated refractory epilepsy (MIT-E). Vatiquinone is a small molecule orally bioavailable compound that has been in development for inherited mitochondrial diseases and related genetic disorders of oxidative stress. Furthermore, companies such as Neuroelectrics, InSightec and BrainSonix are also developing medical devices to tackle DRE. Neuroelectrics is developing Starstim, a device that uses mild electric currents applied on the scalp to calm the abnormal activity of the brain, for the treatment of Drug-resistant epilepsy. The company is certain about the potential of its approach attributable to a reduction in seizure frequency and no device-related adverse events. 

Looking at the current pipeline scenario, DelveInsight estimates that the Drug-resistant epilepsy market dynamics are expected to change positively. Further, an influx of key pharmaceutical companies in the Epileptic domain working in the domain, and a better understanding of the market domain for the study period of 2018–2030.