ICER Report: New Multiple Sclerosis Drugs More Effective, But Safety Concerns Abound
Three relatively new disease-modifying therapies (DMTs) — alemtuzumab, natalizumab, and ocrelizumab — are significantly more effective than other DMTs in the reduction of relapses in relapsing-remitting multiple sclerosis (RRMS), according to the latest Institute for Clinical and Economic Review (ICER) evidence report.1
The ICER report included data from 33 trials of 10 US Food and Drug Administration (FDA)-approved DMTs for MS in the context of the therapeutic goal to decrease the frequency of relapses and prevent further disability. In comparing efficacy of all DMTs with safety, none of the agents in the ICER report were deemed “ideal.”
Annualized Relapse Rates Among DMTs
Three of the 4 relatively new DMTs (alemtuzumab, natalizumab, and ocrelizumab but not daclizumab) showed a reduction in the annualized relapse rate (ARR) of approximately 70% compared with placebo.
The next most effective agents were fingolimod, daclizumab, rituximab, and dimethyl fumarate, collectively producing a 47% to 54% reduction in ARR.
The lowest efficacy (17% to 37% reduction in ARR) was reported in a group of traditional therapies including interferons, glatiramer acetate 20 mg, and teriflunomide.
Slowing Disease Progression
The newly approved agents (including alemtuzumab, ocrelizumab, daclizumab, and natalizumab) showed the most benefits in slowing disability in RRMS compared with placebo (58%, 53%, 46%, and 44% reductions, respectively).
Four older DMTs — interferon β-1a 30 mcg, interferon β-1a 22 mcg, teriflunomide 7 mg, and glatiramer acetate 40 mg — did not demonstrate significant improvements in disease progression. All others had moderate benefits.
Safety
The safest agents were interferons, glatiramer acetate, and teriflunomide. The least safe, due to the risk of progressive multifocal leukoencephalopathy (PML) in patients with positive testing results for the JC virus, were alemtuzumab and natalizumab. Several drugs, including teriflunomide, daclizumab, fingolimod, dimethyl fumarate, ocrelizumab, and natalizumab in JC virus-negative patients, were deemed to have moderate safety compared to all other DMTs.
Value of Therapy Compared to Supportive Care
The ICER group developed a simulation model to estimate the lifetime cost of a particular therapy, taking into account wholesale acquisition cost, dosing, administration, monitoring, and average discounts applied. The estimated lifetime drug cost was then used as a basis of comparison with the costs of supportive care that included inpatient and outpatient care from multiple relapses, disease progression, and ultimate mortality from RRMS. Using this model, the related health care costs over a patient's projected lifetime ranged from approximately $572,000 for alemtuzumab to $1.5 million for daclizumab, compared with approximately $333,300 for supportive care. The model took into account costs from relapses and prevented relapses in RRMS, as well as incremental costs-per-life-year gained and quality-adjusted life years.
Using an acceptable threshold of $150,000 for cost per therapy, compared with supportive care alemtuzumab ($35,000) provided the highest number of quality-adjusted life years gained at a significantly reduced cost compared with all other therapies (range = $185,000 for interferon β-1b 250 mcg to $341,000 for interferon β- 1a 22 mcg).
Overall, the report suggests that the improved clinical benefits of newer agents must continue to be weighed against the risks of safety complications and financial burden over a patient's lifetime.
http://www.neurologyadvisor.com/mult...rticle/637539/
Three relatively new disease-modifying therapies (DMTs) — alemtuzumab, natalizumab, and ocrelizumab — are significantly more effective than other DMTs in the reduction of relapses in relapsing-remitting multiple sclerosis (RRMS), according to the latest Institute for Clinical and Economic Review (ICER) evidence report.1
The ICER report included data from 33 trials of 10 US Food and Drug Administration (FDA)-approved DMTs for MS in the context of the therapeutic goal to decrease the frequency of relapses and prevent further disability. In comparing efficacy of all DMTs with safety, none of the agents in the ICER report were deemed “ideal.”
Annualized Relapse Rates Among DMTs
Three of the 4 relatively new DMTs (alemtuzumab, natalizumab, and ocrelizumab but not daclizumab) showed a reduction in the annualized relapse rate (ARR) of approximately 70% compared with placebo.
The next most effective agents were fingolimod, daclizumab, rituximab, and dimethyl fumarate, collectively producing a 47% to 54% reduction in ARR.
The lowest efficacy (17% to 37% reduction in ARR) was reported in a group of traditional therapies including interferons, glatiramer acetate 20 mg, and teriflunomide.
Slowing Disease Progression
The newly approved agents (including alemtuzumab, ocrelizumab, daclizumab, and natalizumab) showed the most benefits in slowing disability in RRMS compared with placebo (58%, 53%, 46%, and 44% reductions, respectively).
Four older DMTs — interferon β-1a 30 mcg, interferon β-1a 22 mcg, teriflunomide 7 mg, and glatiramer acetate 40 mg — did not demonstrate significant improvements in disease progression. All others had moderate benefits.
Safety
The safest agents were interferons, glatiramer acetate, and teriflunomide. The least safe, due to the risk of progressive multifocal leukoencephalopathy (PML) in patients with positive testing results for the JC virus, were alemtuzumab and natalizumab. Several drugs, including teriflunomide, daclizumab, fingolimod, dimethyl fumarate, ocrelizumab, and natalizumab in JC virus-negative patients, were deemed to have moderate safety compared to all other DMTs.
Value of Therapy Compared to Supportive Care
The ICER group developed a simulation model to estimate the lifetime cost of a particular therapy, taking into account wholesale acquisition cost, dosing, administration, monitoring, and average discounts applied. The estimated lifetime drug cost was then used as a basis of comparison with the costs of supportive care that included inpatient and outpatient care from multiple relapses, disease progression, and ultimate mortality from RRMS. Using this model, the related health care costs over a patient's projected lifetime ranged from approximately $572,000 for alemtuzumab to $1.5 million for daclizumab, compared with approximately $333,300 for supportive care. The model took into account costs from relapses and prevented relapses in RRMS, as well as incremental costs-per-life-year gained and quality-adjusted life years.
Using an acceptable threshold of $150,000 for cost per therapy, compared with supportive care alemtuzumab ($35,000) provided the highest number of quality-adjusted life years gained at a significantly reduced cost compared with all other therapies (range = $185,000 for interferon β-1b 250 mcg to $341,000 for interferon β- 1a 22 mcg).
Overall, the report suggests that the improved clinical benefits of newer agents must continue to be weighed against the risks of safety complications and financial burden over a patient's lifetime.
http://www.neurologyadvisor.com/mult...rticle/637539/
If the risks of Lemtrada become more acceptable for more patients and the demand for it rises, Genzyme will push that subjective "acceptable threshold" by raising the cost by $100,000 to put it in the range of other MS drugs. If other companies are getting $185,000 to $341,000, the marketplace has shown that to be the real "acceptable threshold," not $150,000.
Comment