Treatment Algorithms

March 2009

Treatment Algorithms in Parkinson's Disease

Report Authors
Madhuri Borde, Ph.D.
Nathan Calloway, M.A.

Introduction:

The slow, progressive nature of Parkinson’s disease (PD) results in impaired motor function primarily manifested as resting tremor, bradykinesia, muscle rigidity, and postural instability. The promise of neuroprotection from certain agents, a steadily growing elderly population, the lengthy disease duration (most patients require 10-20 years of therapy), and the use of combination therapies will drive growth in the PD market. For the past 30 years, the gold-standard treatment for PD has been levodopa therapy, and most drug development has centered on adjunct or levodopa-sparing therapies. These efforts have led to widespread use of Boehringer Ingelheim’s Mirapex (pramipexole) and ropinirole (GlaxoSmithKline’s Requip, generics; Requip XL) in PD treatment. Our analysis of patient-level claims data shows that Teva’s monoamine oxidase-B (MAO-B) inhibitor Azilect (rasagiline) has emerged as a key competitor to Mirapex and ropinirole, particularly in early-stage patients, in large part because it is the first agent to offer evidence of neuroprotection. Using patient-level claims data, as well as insight from 150 surveyed neurologists and primary care physicians (PCPs), this report determines the share of each currently marketed drug by line of therapy, analyzes why key drugs are chosen over others, and explains how physicians believe this dynamic will change over the next two years.

Questions Answered in This Report:

  *   Lines of therapy: Levodopa-carbidopa’s unquestionable efficacy has led it to dominate much of PD treatment. How much of first-line patient share is devoted to levodopa formulations compared with levodopa-sparing therapies, and do surveyed neurologists and PCPs approach first-line treatment differently? How many patients in first- and second-line therapy receive Mirapex or Requip versus Azilect? What percentage of patients who start with Mirapex or Requip switch to another agent within one year? How many surveyed physicians prescribe generic ropinirole and are likely to do so in the next two years, and how often do they currently use it ahead of other dopamine agonists? What do surveyed physicians view as the leading advantages of Requip XL over Mirapex, and how do they currently prescribe the newly launched once-daily dopamine agonist?

  *   Pathways to key therapies: Our analysis of patient-level claims data shows that while PD patients continue to be treated with the traditional combination of levodopa plus a dopamine agonist, MAO-B inhibitor, or catechol-O-methyltransferase (COMT) inhibitor, physicians are being more aggressive about combining levodopa-sparing agents before moving to levodopa. Which agents do patients use most often directly before starting levodopa? How does this distribution change with neurologists versus PCPs? What percentage of patients moving to levodopa from each drug discontinue their prior therapy versus continue it as an adjunct? What do our data suggest about Mirapex’s versus ropinirole’s positioning in lines of therapy? How did physicians use UCB’s Neupro (transdermal rotigotine) during the time it was available in the United States? What does the pattern of agents used prior to Novartis/Orion’s Stalevo (entacapone/levodopa/carbidopa) suggest about this agent’s use versus use of levodopa?

  *   Physician behavior: Although approximately one-third of the patients in the care of PCPs that we surveyed are younger than age 65, PCPs are much less likely than surveyed neurologists to turn to dopamine agonists first line for patients in this age-group. To what percentage of their patients do surveyed PCPs prescribe a dopamine agonist first line broken out by age and disease stage, and how do these estimates compare with those for surveyed neurologists? Which agents are more commonly used by neurologists and PCPs to treat PD? Do the barriers to treatment initiation differ between these two physician specialties?

  *   Forecast: Our survey data indicate that treatment of PD in the primary care versus the specialist setting will continue to differ through 2011. How will surveyed physicians’ use of Azilect change by line of therapy over the next two years? How are surveyed physicians most likely to use generic ropinirole over the next two years? How do physicians currently use Requip XL by line of therapy, and how will its use evolve over the next two years?

Scope:

Includes:

Primary research: Quantitative results from our survey of 150 physicians (75 neurologists and 75 PCPs):

- Physician opinion on how drug use differs by disease severity.

- Most influential drug attributes when physicians choose between agents.

- Anticipated changes in the line of therapy in which physicians use key agents.

Primary patient-level data: Quantitative findings from our analysis of data covering 61 million lives from 98 geographically diverse U.S. health plans:

- Quantified lines of therapy analysis showing the exact share of each agent in each line of therapy, including rate of progression between lines and length of time patients are on each line.

- Progression flowcharts through one year of treatment for newly diagnosed patients receiving each of the following first line agents: levodopa-carbidopa fixed-dose combinations (FDCs) (generics), Bristol-Myers Squibb's Sinemet/Sinemet CR (levodopa-carbidopa), UCB’s Parcopa (levodopa-carbidopa), Mirapex, Requip, Neupro, other dopamine agonists, Somerset Pharmaceuticals' Eldepryl (selegiline), Valeant’s Zelapar (selegiline), Bristol-Myers Squibb's Emsam (selegiline), other selegilines (generics), Azilect, Novartis's Comtan (entacapone), Stalevo, Valeant’s Tasmar (tolcapone), amantadine (Endo Pharmaceuticals’ Symmetrel, generics), anticholinergic agents, Eisai/Pfizer’s Aricept (donepezil), Janssen/Ortho-McNeil Neurologics’ Razadyne/Razadyne ER (galantamine), Novartis’s Exelon (rivastigmine) and Exelon Patch, and antipsychotic agents.

- Flowcharts tracking the preceding therapy patterns for patients taking each of the following key therapies: Parcopa, other levodopa-carbidopa formulations, Mirapex, Requip, Neupro, Comtan, Stalevo, Azilect, Zelapar, amantadine, Aricept, and Exelon Patch.

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