Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting multiple organ systems, manifesting at various levels of severity, and involving periods of remission and relapse. The autoimmune reactions that characterize SLE can result in severe organ damage and, in some instances, ultimately lead to death. In 2011, IV belimumab (GlaxoSmithKline’s Benlysta) became the first drug approved for SLE in more than 50 years, highlighting the difficulty of successfully bringing to market agents to treat this multifactorial disease. Several biological therapies are in late-stage development for SLE, but based on the most recently reported trial data, significant opportunity remains for drugs that reliably reduce disease activity and corticosteroid use.
Questions Answered in This Report:
- A drug’s performance on several efficacy end points, including the percentage of patients able to reduce their oral corticosteroid dose to ≤ 7.5 mg/day prednisone at 52 weeks, 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 rheumatologists weight efficacy measures and other drug attributes in their prescribing decisions for moderate to severe SLE?
- Therapies with an improved effect on renal organ domain scores, a greater efficacy in reducing disease activity, an improved ability to spare corticosteroid use, and greater ability to offer improvement in health-related quality of life are key areas of unmet need for moderate to severe SLE according to the insights of surveyed U.S. and European rheumatologists. Which therapies in development for moderate to severe SLE 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. managed care organization pharmacy directors (MCO PDs) seek from new therapies on key clinical attributes for which surveyed physicians indicate there is high unmet need?
- A therapy’s effect on disease activity and ability to reduce corticosteroid use are key drivers of physicians’ prescribing decisions and/or are a focus of drug development for new moderate to severe SLE therapies. What trade-offs across these and other clinical attributes are U.S. rheumatologists willing to make when considering the use of emerging therapies for the treatment of moderate to severe SLE? Based on the trade-offs in price and performance across key drug attributes that U.S. rheumatologists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for moderate to severe SLE?
- Based on its clinical profile, rituximab (Biogen Idec/Roche/Genentech/Chugai/Zenyaku Kogyo’s Rituxan, Roche’s MabThera) is the current clinical gold standard in our Drug Comparator Model. What attributes do thought leaders believe differentiate this therapy from competing current therapies and emerging therapies? Will any therapies in development challenge rituximab as the future gold standard in 2017 or 2022?
Attributes included in conjoint analysis-based assessment of target product profiles for moderate to severe SLE (excluding severe active renal and severe active CNS):
- Effect on disease activity at 52 weeks (placebo-adjusted composite responder rate).
- Reduction in use of corticosteroids at 52 weeks (percentage of patients who reach ≤ 7.5 mg/day).
- Rate of flares (percentage of patients).
- Improvement in health-related quality of life score (SF-36 PCS) at 52 weeks.
- Risk of serious infections (percentage of patients).
- Drug formulation.
Attributes included in assessment of U.S. payers’ receptivity to new therapies for moderate to severe SLE (excluding severe active renal and severe active CNS):
- Effect on disease activity (placebo-adjusted percentage of patients achieving a response on a composite responder index).
- Effect on flares (placebo-adjusted percentage of patients experiencing a severe flare).
- Time to response.
- Reduction in use of corticosteroids.
Physicians surveyed: 61 U.S. and 30 European rheumatologists.
Payers surveyed: 20 U.S. MCO PDs.
Comprehensive List of Therapies Included in Our Research and Modeling:
- IV belimumab (GlaxoSmithKline’s Benlysta)
- Rituximab (Biogen Idec/Roche/Genentech/Chugai/Zenyaku Kogyo’s Rituxan, Roche’s MabThera)
- Mycophenolate mofetil (Roche/Galenica’s CellCept, generics)
- Subcutaneous belimumab (GlaxoSmithKline’s Benlysta)
- Epratuzumab (UCB)
- Blisibimod (Anthera Pharmaceuticals)
- Rigerimod (ImmuPharma’s Lupuzor, P140)
- Tabalumab (Eli Lilly’s LY-2127399)
- Atacicept (Merck Serono)
- Rontalizumab (Genentech/Chugai)