DecisionBase

June 2013

Epilepsy

Introduction:

What Type and Magnitude of Clinical Improvements Over Current Mainstays of Treatment Would Make Neurologists and Payers Receptive to a New Therapy?

Approximately one-third of all epilepsy patients have uncontrolled seizures despite treatment with currently marketed antiepileptic drugs (AEDs). With a diagnosed prevalent epilepsy population in excess of 5 million patients across the major pharmaceutical markets we cover (United States, France, Germany, Italy, Spain, United Kingdom, and Japan), significant unmet need remains for effective therapies for the sizable treatment-refractory epilepsy population. Several recently launched agents to treat partial-onset seizures in treatment-refractory patients offer novel mechanisms of action and/or potential for therapeutic gains over current mainstays. However, interviewed epilepsy experts doubt that these newer agents will revolutionize the management of this perennially underserved subgroup of patients; thus, opportunity remains for new therapies offering meaningful clinical improvements in a range of areas, in particular efficacy response.

Questions Answered in This Report:

  *   A drug’s performance on at least seven efficacy end points, including increase in the 50% responder rate, is important for drug approval and physician use. What are the key primary and secondary clinical trial end points with which new therapies are evaluated? How do U.S. and European neurologists weight efficacy measures and other drug attributes in their prescribing decisions for partial-onset seizures in treatment-refractory epilepsy patients?

  *   A greater effect on the percentage of seizure-free patients and a lower risk of somnolence and fatigue are key areas of unmet need for epilepsy according to the insights of surveyed U.S. and European neurologists. Are therapies in development for partial-onset seizures in treatment-refractory patients poised to fulfill these needs? What clinical and/or regulatory challenges must drug developers overcome in order to capitalize on these areas of unmet need? What degree of improvement over currently available therapies do surveyed U.S. MCO PDs seek from new therapies on key clinical attributes for which surveyed physicians indicate there is high unmet need?

  *   A drug’s reduction in partial-onset seizure frequency and increase in 50% responder rate as an adjunctive therapy are key drivers of physicians’ prescribing decisions and/or are the focus of drug development for new epilepsy therapies. What trade-offs across these and other clinical attributes are U.S. neurologists willing to make when considering the use of emerging therapies for the treatment of epilepsy? Based on the trade-offs in price and performance across key drug attributes that U.S. neurologists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for partial-onset seizures in treatment-refractory epilepsy patients?

  *   Despite the potential launch of several emerging therapies in the epilepsy market over the next ten years, levetiracetam immediate-release (IR) (UCB/Otsuka Pharmaceuticals’ Keppra/E Keppra, generics) will remain the gold-standard therapy in our Drug Comparator Model. On what clinical attributes is levetiracetam IR most differentiated from its competitors? What are the weaknesses of this therapy on which emerging therapies can capitalize? Which emerging therapies, if any, pose the greatest threat to levetiracetam IR as well as the other key current therapies?

Scope:

Attributes included in conjoint analysis based assessment of target product profiles for partial-onset seizures in treatment-refractory epilepsy patients:

- Adjunctive therapy: reduction from baseline in partial-onset seizure frequency (placebo-adjusted).

- Adjunctive therapy increase in 50% responder rate (placebo-adjusted).

- Conversion to monotherapy: percentage of patients successfully completing a conversion-to-monotherapy trial (control-adjusted).

- Incidence of serious or life-threatening side effects.

- Incidence of psychiatric side effects.

- Dosing frequency.

- Price per day.

Attributes included in assessment of U.S. payers’ receptivity to new therapies for partial-onset seizures in treatment-refractory epilepsy patients:

- Reduction in partial-onset seizure frequency as an adjunctive therapy in adult treatment-refractory epilepsy patients.

- Reduction in partial-onset seizure frequency as an adjunctive therapy in pediatric treatment-refractory epilepsy patients (aged 4 or older).

- Percentage of adult treatment-refractory epilepsy patients successfully completing a conversion to monotherapy trial.

- Incidence of psychiatric side effects.

Physicians surveyed: 61 U.S. and 32 European neurologists.

Payers surveyed: 20 U.S. MCO PDs.

Comprehensive List of Therapies Included in Our Research and Modeling:

Current Therapies

- Levetiracetam immediate-release (IR) (UCB/Otsuka Pharmaceuticals Keppra/E Keppra, generics)

- Lamotrigine IR (GlaxoSmithKline/Juste’s Lamictal/Labileno/Elmendos/Crisomet, generics)

- Oxcarbazepine IR (Novartis’s Trileptal/Tolep, generics)

- Lacosamide (UCB’s Vimpat)

- Ezogabine/retigabine (GlaxoSmithKline/Valeant’s Potiga/Trobalt)

Emerging Therapies

- Perampanel (Eisai’s Fycompa)

- Brivaracetam (UCB’s Rikelta)

- Topiramate extended-release (XR) (Upsher-Smith’s USL-255)

- Oxcarbazepine XR (Supernus’s Oxtellar XR)

- Pregabalin controlled-release (CR) (Pfizer’s Lyrica CR)


Search Reports

Mentioned in this report:

  • - AbbVie
  • - Bial
  • - Eisai
  • - GlaxoSmithKline
  • - Impax Laboratories
  • - Janssen-Cilag
  • - Juste
  • - Kyowa Hakko Kirin
  • - Novartis
  • - Otsuka Pharmaceuticals
  • - Pfizer
  • - Sunovion
  • - Supernus
  • - UCB
  • - Upsher-Smith
  • - Valeant
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