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, as they are simple to use and safe. GSK has managed to slow the ensuing generic erosion of Lamictal/Lamictal XR, but UCB has not been so successful with Keppra/Keppra XR, and now only sees significant sales in Japan.
- Keppra/Keppra XR and Lamictal/Lamictal XR sales will fall 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 US 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 syndromes market, there will be a greater demand for higher rates of seizure reduction and improved tolerability. Fintepla, for example, has shown unparalleled efficacy in trials in Dravet syndrome, 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.
- Key recent events in this space include a supplemental US approval and positive CHMP opinion for UCB’s Fintepla for the treatment of LGS, while the drug also launched for Dravet syndrome in Japan in September 2022. Additionally, the US launch of Marinus’s Ztalmy for the treatment of CDKL5 deficiency disorder occurred in July 2022. The launch 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 in early 2023. Sun Pharmaceutical’s Sezaby for the treatment of neonatal seizures in full-term and preterm infants was approved in November 2022, as was Azurity’s Zonisade for POS in July 2022. Finally, positive long-term safety and efficacy data were recently released for Xenon’s pipeline asset XEN1101 in POS.
- 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.
- Pipeline drugs in development include Takeda’s soticlestat, which is in Phase III trials for Dravet syndrome and LGS. Though the drug trails behind other assets in the rare epilepsy syndromes market, its unique mechanism, robust efficacy, and extremely attractive safety and tolerability profile maintain its potential to carve out a place in this market segment. Additionally, Xenon’s XEN1101, a next-generation Kv7 potassium channel regulator, has demonstrated significant efficacy in trials and a favorable tolerability profile. As a therapy with the potential to improve seizure frequency and depression, a significant co-morbidity seen in this patient population, XEN1101 has the capacity to capture significant market share within the space.
- Marinus’s Ztalmy (oral ganaxalone) is being evaluated beyond CDKL5 deficiency disorder for use in tuberous sclerosis complex. A second-generation oral suspension is also in early-stage development, with the aim of providing enhanced efficacy, an improved safety profile, reduced dosing frequency, and better absorption. An intravenous formulation of ganaxalone is being evaluated for patients with refractory status epilepticus, for which there is currently a paucity of treatment options.
- There are numerous high-impact upcoming events expected in the epilepsy space, including a European approval decision for Ztalmy in CDKL5 deficiency disorder, as well as Phase III data for the same drug in status epilepticus (RAISE trial).
CONTENTS
7 OVERVIEW
7 Latest key takeaways
9 DISEASE BACKGROUND
9 Definition
9 Patient segmentation
10 Risk factors
10 Diagnosis
12 TREATMENT
12 Treatment guidelines
14 Drug approaches
15 Non-drug approaches
16 EPIDEMIOLOGY
16 Prevalence methodology
19 MARKETED DRUGS
27 PIPELINE DRUGS
36 KEY REGULATORY EVENTS
36 Zydus Sets Sight On First US Generic Of UCB’s Briviact
36 Food Fight Ahead As FDA Gives Tentative Libervant Nod
36 Topiramate Review Follows Safety Signal Assessment
37 England Okays Funding For Revestive, Jyseleca & Fintepla
37 UCB’s Zogenix Bet Pays Out Quickly With Fresh Fintepla Approval
37 ANDA Sponsors Swarm On Vimpat Blockbuster As Protection Expires
38 Marinus, With Ztalmy Approval, Takes First Step Into Seizure Disorder Market
39 PROBABILITY OF SUCCESS
40 LICENSING AND ASSET ACQUISITION DEALS
40 Kriya Bulks Up Preclinical Portfolio With New Neurology Focus
40 Aquestive Licenses Lennox-Gastaut Therapy To Assertio Affiliate
40 Aquestive Licenses Ex-US Libervant Rights To Pharmanovia
40 SK Biopharm Partners With Eurofarma On Latin American Cenobamate Rights
41 Neuraxpharm Boosts Branded Business With Established Sanofi Portfolios
41 Biohaven Acquires Channel Biosciences
42 Aculys Obtains Japan, Asia-Pacific Rights To Neurelis Epilepsy Drug
42 UCB Jumps Early Onto M&A Merry-Go-Round With Zogenix Buy
42 SK Biopharmaceuticals Partners With Biorchestra
42 Ovid Starts Neurology Spree With AstraZeneca Deal
44 CLINICAL TRIAL LANDSCAPE
45 Sponsors by status
46 Sponsors by phase
48 DRUG ASSESSMENT MODEL
48 Generalized/POS antiepileptic drugs
49 Rare/pediatric epilepsy syndrome drugs
50 Pipeline antiepileptic drugs
52 MARKET DYNAMICS
53 FUTURE TRENDS
53 Drugs approved for rare pediatric epilepsies will deliver large revenues
53 Large POS market is highly saturated and will be difficult to penetrate
54 Key epilepsy player UCB will follow new strategies and lifecycle management to maintain market share
55 CONSENSUS FORECASTS
60 RECENT EVENTS AND ANALYST OPINION
60 NBI-827104 for Partial Seizures (Epilepsy) (December 6, 2022)
60 STK-001 for Dravet Syndrome (Epilepsy) (December 5, 2021)
61 XEN1101 for Partial Seizures (Epilepsy) (October 4, 2021)
63 STK-001 for Dravet Syndrome (Epilepsy) (September 21, 2021)
65 KEY UPCOMING EVENTS
66 KEY OPINION LEADER INSIGHTS
66 Refractory epilepsy patients
66 Rare pediatric epilepsies
67 UNMET NEEDS
67 Treatment-resistant epilepsy patients
67 Effective medicines available for specific epilepsy syndromes
67 Better treatment options for the common co-morbidities of epilepsy patients
68 BIBLIOGRAPHY
69 APPENDIX
LIST OF FIGURES
9 Figure 1: ILAE 2017 Classification of Seizure Types: Basic Version
12 Figure 2: Levels of efficacy and effectiveness evidence supporting use of AEDs in epilepsy subpopulations
14 Figure 3: Recommendations for monotherapy in adults with new-onset epilepsy with focal epilepsy or unclassified tonicclonic seizures
15 Figure 4: Drug approaches for treating various types of epilepsy
18 Figure 5: Trends in prevalent cases of active epilepsy, 2018–27
27 Figure 6: Overview of pipeline drugs for epilepsy in the US
27 Figure 7: Pipeline drugs for epilepsy, by company
28 Figure 8: Pipeline drugs for epilepsy, by drug type
28 Figure 9: Pipeline drugs for epilepsy, by classification
39 Figure 10: Probability of success in the epilepsy pipeline
44 Figure 11: Clinical trials in epilepsy
44 Figure 12: Top 10 drugs for clinical trials in epilepsy
45 Figure 13: Top 10 companies for clinical trials in epilepsy
45 Figure 14: Trial locations in epilepsy
46 Figure 15: Epilepsy trials status
47 Figure 16: Epilepsy trials sponsors, by phase
48 Figure 17: Datamonitor Healthcare’s drug assessment summary for epilepsy
52 Figure 18: Market dynamics in epilepsy
53 Figure 19: Future trends in epilepsy
63 Figure 20: XEN1101 for Partial Seizures (Epilepsy) (October 4, 2021): Phase IIb – X-TOLE
65 Figure 21: Key upcoming events in epilepsy
LIST OF TABLES
17 Table 1: Prevalent cases of active epilepsy, 2018–27
20 Table 2: Marketed drugs for epilepsy
29 Table 3: Pipeline drugs for epilepsy in the US
56 Table 4: Historical global sales, by drug ($m), 2017–21
58 Table 5: Forecasted global sales, by drug ($m), 2022–26
60 Table 6: NBI-827104 for Partial Seizures (Epilepsy) (December 6, 2022)
61 Table 7: STK-001 for Dravet Syndrome (Epilepsy) (December 5, 2021)
62 Table 8: XEN1101 for Partial Seizures (Epilepsy) (October 4, 2021)
64 Table 9: STK-001 for Dravet Syndrome (Epilepsy) (September 21, 2021)