Introduction:How Will the Complex Interplay Between Benefit, Risk, and Cost Impact Prescriber Preferences, and Payer Acceptance of, Future Disease-Modifying Therapies?
The market for disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis (RR-MS) is highly active and commercially compelling. In spite of a small diagnosed prevalent population relative to many other neurological indications, drug-treatment rates for RR-MS are high, and neurologists emphasize early intervention and long-term treatment to improve long-term outcomes in this chronic disease. The number of disease-modifying therapies approved to treat RR-MS is expanding steadily, including the availability of multiple oral disease-modifying drugs in this historically injectable market. However, because the MS disease course is heterogeneous and therapeutic response is unpredictable, a continued need exists for more-effective, more-tolerable, and less-burdensome treatment alternatives.
Questions Answered in This Report:
A drug’s performance on eight efficacy end points, including a reduction in the risk of sustained disability progression as measured by the Expanded Disability Status Scale (EDSS) over two years, 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 RR-MS?
Glatiramer acetate (Teva’s Copaxone) is the 2012 major-market sales leader for RR-MS. What weaknesses exist in its profile that would allow emerging therapies to gain traction in the market? Have emerging therapies demonstrated strengths on the attributes that surveyed neurologists indicate are the most important in their prescribing decisions? Which emerging therapies will offer the clinical improvements over currently available therapies that surveyed MCO PDs seek from new therapies?
Reduction in the risk of annualized relapse rate and price per day are key drivers of physicians’ prescribing decisions. 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 RR-MS? 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 RR-MS?
Dimethyl fumarate (Biogen Idec’s Tecfidera) and alemtuzumab (Genzyme/Sanofi/Bayer HealthCare’s Lemtrada; awaiting U.S. approval) share future gold standard status in our Drug Comparator Model because of their superior clinical profiles over the key current therapies we evaluated. On what clinical attributes are dimethyl fumarate and alemtuzumab most differentiated from their competitors? Which current therapies are at greatest risk of being replaced by dimethyl fumarate and alemtuzumab?
Attributes included in conjoint analysis based assessment of target product profiles for RR-MS:
- Reduction in annualized relapse rate (ARR) relative to placebo.
- Reduction in risk of three-month sustained disability progression (i.e., Kurtzke Expanded Disability Status Scale [EDSS] progression) relative to placebo.
- Reduction in brain atrophy relative to placebo.
- Incidence of serious or life-threatening side effects (e.g., opportunistic infections, bradycardia, autoimmune adverse events, malignancy, cardiac risk).
- Incidence of less-serious side effects (e.g., injection-site reactions, flu-like symptoms, flushing).
- Monitoring burden: frequency (e.g., first-dose only, monthly) and complexity (e.g., number/difficulty of unique tests, need for referrals).
Attributes included in assessment of U.S. payers’ receptivity to new therapies for RR-MS:
- Effect on ARR.
- Effect on risk of three-month sustained disability progression.
- Monitoring burden: the combined frequency and complexity (e.g., number of unique tests [laboratory/blood, urinalysis, MRI, cardiac], need for physician referrals) of monitoring required.
- Burden of delivery: dosing frequency and formulation.
Physicians surveyed: 60 U.S. and 31 European neurologists.
Payers surveyed: 30 U.S. MCO PDs.
Comprehensive List of Therapies Included in Our Research and Modeling:
- Glatiramer acetate (Teva’s Copaxone)
- IFN-β-1a (IM) (Biogen Idec’s Avonex)
- Natalizumab (Biogen Idec’s Tysabri)
- Fingolimod (Novartis/Mitsubishi Tanabe Pharma’s Gilenya/Imusera)
- Dimethyl fumarate (Biogen Idec’s Tecfidera)
- Pegylated IFN-β-1a (SC; Biogen Idec’s Plegridy)
- Alemtuzumab (Genzyme/Sanofi/Bayer HealthCare’s Lemtrada; approved in Europe in 2013)
- Daclizumab (AbbVie/Biogen Idec)
- Orelizumab (Roche/Genentech)
- Laquinimod (Teva/Active Biotech’s Nerventra)