DecisionBase

April 2013

Parkinson’s Disease (Intermediate Through Advanced)

Introduction:

How Do Surveyed Neurologists and Payers Perceive New Therapies for Levodopa-Induced Dyskinesias?

We expect that the prevalence of Parkinson’s disease (PD) will approach 3 million cases in the major pharmaceutical markets in 2021, with a substantial fraction of patients who are in the intermediate through advanced disease stage and are experiencing levodopa-induced motor response complications (MRCs), such as motor fluctuations and dyskinesias. MRCs present one of the primary ongoing clinical challenges in the management of PD and thus present a viable opportunity for new therapeutic agents. The PD pipeline is rich with emerging therapies, some of them targeting MRCs, including reformulations of current agents, new drugs from current PD drug classes, and therapies with new-to-PD mechanisms of action, such as adenosine A2A receptor antagonists and metabotropic glutamate receptor modulators. However, whether therapies in development will fulfill the remaining unmet need to better address MRCs—and to what extent they might fulfill this need—remains to be seen.

Questions Answered in This Report:

  *   A drug’s performance on at least eight efficacy end points, including increase in duration of “on” time/decrease in duration of “off” time, is important for drug approval and physician uptake. What are the key primary and secondary clinical trial end points with which new therapies for intermediate through advanced PD are evaluated? How do U.S. and European neurologists weight efficacy measures and other drug attributes in their prescribing decisions for intermediate through advanced PD?

  *   Better management of psychotic, cognitive, and/or or mood symptoms, increased “on” time without also worsening dyskinesias, and better management of MRCs in general are key areas of unmet need for intermediate through advanced PD according to the insights of surveyed U.S. and European neurologists. Which therapies in development for PD are poised to fulfill these needs? What clinical and/or regulatory challenges must drug developers overcome 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?

  *   The effect on levodopa-induced dyskinesias and effect on “on” time without troublesome dyskinesias are key drivers of physicians’ prescribing decisions and/or are the focus of drug development for new PD 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 intermediate through advanced PD? 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 intermediate through advanced PD?

  *   Based on its clinical profile, pramipexole extended-release (ER; Boehringer Ingelheim’s Mirapex ER/Mirapexin ER/Sifrol Retard/Mirapex LA) and rotigotine (UCB/Otsuka Pharmaceutical’s Neupro/Neupro Patch/Leganto) are the two current clinical gold standards in our Drug Comparator Model. What attributes do thought leaders believe differentiate these therapies from competing current therapies and emerging therapies? Will any therapies in development challenge pramipexole ER and rotigotine as the future gold standard in 2016 or 2021?

Scope:

Attributes included in conjoint-analysis-based assessment of target product profiles for anti-dyskinesia agents in intermediate through advanced PD:

- Effect on levodopa-induced dyskinesias (e.g., frequency, severity)

- Effect on total daily “on” time (hours per day)

- Effect on “on” time without troublesome dyskinesias (hours per day)

- Effect on primary motor symptoms (UPDRS Part III score)

- Risk of hallucinations (% of patients)

- Dosing frequency

- Price per day

Attributes included in assessment of U.S. payers’ receptivity to new therapies for intermediate through advanced PD:

- Delivery improvements over levodopa (Bristol-Myers Squibb/DuPont Pharma’s Sinemet, Sinemet CR, other brands, generics)

- Effect on motor fluctuations (reduction in daily “off” time) for a levodopa-adjunct therapy 

- Effect on dyskinesias for a levodopa-adjunct therapy

- Effect on psychosis (alleviating psychotic symptoms) for a levodopa-adjunct therapy

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

Payers surveyed: 22 U.S. MCO PDs

Comprehensive List of Therapies Included in Our Research and Modeling:

Current Therapies

- Rasagiline (Teva/Lundbeck’s Azilect)

- Pramipexole extended-release (ER; Boehringer Ingelheim’s Mirapex ER/Mirapexin ER/Sifrol Retard/Mirapex LA)

- Rotigotine (UCB/Otsuka Pharmaceutical’s Neupro/Neupro Patch/Leganto)

- Entacapone (Novartis/Orion Pharma’s Comtan/Comtess/Stalevo, generics)

- Amantadine (Novartis/Alliance Pharma’s Symmetrel, other brands, generics)

Emerging Therapies

- Mavoglurant (AFQ-056; Novartis)

- ADS-5102 (Adamas Pharmaceuticals’ Nurelin)

- IPX-066 (Impax Laboratories/GlaxoSmithKline’s Rytary)

- Preladenant (Merck)

- Safinamide (Newron Pharmaceuticals/Zambon Pharma/Meiji Seika Pharma)


Search Reports

Mentioned in this report:

  • - Acadia Pharmaceuticals
  • - Adamas Pharmaceuticals
  • - Addex Therapeutics
  • - Alliance Pharma
  • - Biotie Therapies
  • - Boehringer Ingelheim
  • - Bristol-Myers Squibb
  • - DuPont Pharma
  • - GlaxoSmithKline
  • - Impax Laboratories
  • - Kyowa Hakko Kirin
  • - Lundbeck
  • - Meiji Seika Pharma
  • - Merck & Co.
  • - Newron Pharmaceuticals
  • - Novartis
  • - Orion Pharma
  • - Otsuka Pharmaceutical
  • - Teva Pharmaceutical Industries
  • - UCB
  • - Zambon Pharma
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