Introduction:Which Clinical Attributes Will Most Effectively
Position Emerging Biologics Against IV Belimumab in the Moderate to Severe
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 (Human
Genome Sciences/GlaxoSmithKline’s Benlysta) became the first drug approved for
SLE in more than 50 years, highlighting the difficulty in 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 at least eight efficacy end points,
including the percent 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 a lower risk of serious infections 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 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 therapy’s effect on
disease activity and the risk of serious infections with which it is associated
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 2016 or 2021?
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)
score 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: 60 U.S. and 30 European
Payers surveyed: 21
U.S. MCO PDs
Comprehensive List of Therapies Included in Our Research and
- IV belimumab (Human Genome Sciences/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 (Human Genome Sciences/GlaxoSmithKline)
- Epratuzumab (Immunomedics/UCB)
- Blisibimod (Anthera Pharmaceuticals)
- Forigerimod (ImmuPharma’s Lupuzor, P140, CEP-33457)
- Tabalumab (Eli Lilly’s LY-2127399)
- Atacicept (Merck Serono)
- Rontalizumab (Genentech/Chugai)