Disease Analysis: Epilepsy

Disease Overview

Epilepsy is characterized by recurrent, unprovoked seizures, and is one of the most common chronic neurological disorders globally. A seizure is a transient manifestation of signs and/or symptoms, including a disturbance of consciousness, emotion, behavior, or motor function, which occurs because of abnormal excessive or synchronous neuronal activity in the brain.

Latest key takeaways

• Datamonitor Healthcare estimates that in 2021, there were 55.8 million prevalent cases of active epilepsy worldwide, and forecasts that number to increase to 59.0 million prevalent cases by 2027.
• The traditional antiepileptic drug (AED) market is highly genericized and there are limited branded AEDs left without generic equivalents. Additionally, though these newer branded AEDs differentiate themselves from older ones, there are still unmet needs in this market to be addressed, including refractory epilepsy and rare specific epilepsies.
• The partial-onset seizure (POS) market represents the largest market in the epilepsy disease space; however, it is highly saturated with an extensive repertoire of anticonvulsants available for prescription. Primary drugs in this patient segment are the broad-label leaders Keppra/Keppra XR, Lamictal/Lamictal XR, and Vimpat. GlaxoSmithKline has managed to slow the ensuing generic erosion of Lamictal/Lamictal XR, but UCB has not been so successful with Keppra/Keppra XR, and sees significant sales only remaining in Japan.
• Keppra/Keppra XR and Lamictal/Lamictal XR sales will continue to plummet as increasing numbers of generic levetiracetam and lamotrigine drugs threaten their respective market shares. UCB’s high-performing Vimpat is also now facing generic erosion, with the first generics released in April 2022. Brand and company reputation will help to offset the decrease in sales, particularly with Lamictal/Lamictal XR, but attention will turn to the follow-on brands (Fycompa and Xcopri) to preserve market share from ensuing generics. UCB will continue to encourage physicians to opt for its newer branded products Briviact or Vimpat in order to maintain its market-leading position in the epilepsy space.
• The breadth of each drug’s label is highly pertinent to its competitive edge and provides impetus for the ongoing uptake of branded antiepileptics. Even in the saturated POS market, numerous label expansions broadening POS drug usage to monotherapy use and the treatment of pediatric patients are likely to bolster uptake. Further expansion to generalized and secondary generalized seizures, specific subpopulations such as refractory epilepsy patients, and rare pediatric epilepsy patients may also help to maximize commercial potential.
• Despite the rare niche epilepsy syndromes encompassing much smaller patient populations, companies which successfully achieve approval in these indications should be able to gain higher returns for their therapies. This is because there are so few drugs, or none in some circumstances, that have been specifically approved for indications such as Lennox-Gastaut syndrome (LGS), Dravet syndrome, PCDH19 epilepsy, and CDKL5 epilepsy. The lack of competition in comparison to the larger generalized and POS market segments combined with the large unmet need will mean these drugs are likely to be priced at a premium. Epidiolex, for example – the first plant-derived prescription cannabinoid approved in the US for Dravet syndrome – faces little competition and therefore can justify a higher price.
• Potential competitors are catching up, however, with more drugs in this segment being approved or nearing submission. As more drugs enter the rare epilepsy syndrome market, there will be a greater demand for higher rates of seizure reduction and improved tolerability. Fintepla, for example – the newest entrant in Dravet syndrome – has shown unparalleled efficacy in trials but is hindered by its safety/tolerability profile. As new and distinguished compounds become available in this patient segment, market share will be absorbed from former leaders in the space.
• The most pressing unmet needs in the epilepsy area have remained consistent over the past several years. Primary unmet needs include additional treatment options for refractory epilepsy patients, effective medicines for specific epilepsy syndromes such as PCDH19 epilepsy and CDKL5 syndrome, and better ways to manage common co-morbidities afflicting epilepsy patients.
• Some key recent events in this space include the supplemental US approval of Zogenix’s Fintepla for the treatment of LGS and the US approval of Marinus’s Ztalmy for the treatment of CDKL5 deficiency disorder (both events occurred in March 2022). The approval of Ztalmy is significant as it is the first treatment indicated for use in CDKL5 deficiency disorder, and the drug therefore faces minimal competition. A corresponding EU filing for Ztalmy was submitted in October 2021, with a CHMP opinion expected towards the end of 2022. In the POS epilepsy space, UCB’s supplemental NDA for Briviact has recently been approved in Europe and involved the expansion of treatment for children from two years of age (previously from four years of age). In the US, the FDA has granted approval to expand the treatable patient population for Briviact to individuals aged one month and older.
• SK Biopharmaceuticals’ Xcopri was approved by the FDA for the treatment of POS epilepsy in adults in November 2019, and by the EMA in March 2021. The drug exhibited cases of drug reaction with eosinophilia and systemic symptoms (DRESS) in Phase II clinical trials. However, results from a large Phase III open-label extension study of Xcopri as an adjunctive treatment in POS epilepsy patients have shown that a slower titration rate than that utilized in earlier studies mitigates the risk of DRESS syndrome occurring. These results permitted the omission of a black box warning for DRESS syndrome on Xcopri’s prescribing information. Xcopri’s efficacy trial data are extremely encouraging in refractory epilepsy patients and in achieving seizure freedom, setting the drug up well for garnering POS market share.
• There are several key upcoming events expected in the epilepsy space, including a PDUFA decision for Libervant (seizure clusters) and a European approval decision for Ztalmy (CDKL5 deficiency disorder).