ALS Association Objects to Use of ‘Failed’ Cost-effectiveness Measures
The ALS Association has formally objected to the use of two controversial measures of cost-effectiveness in the upcoming evaluations of AMX0035 and oral edaravone, which are being reviewed as treatments for amyotrophic lateral sclerosis (ALS) in the U.S.
These cost-effectiveness measures fail to value the lives of ALS patients, the objections claim.
The written objections were filed with the Institute for Clinical and Economic Review, known as ICER, during a comment period for a draft scoping document. The document outlined how the institute plans to conduct cost-effectiveness analyses of these potential ALS therapies, currently under regulatory review in the U.S.
ICER is a nonprofit organization whose assessments of cost-effectiveness increasingly influence medicines’ price negotiations and reimbursements in the U.S.
“ICER’s model is built on assumptions that don’t make sense for the ALS community, that fail to capture the engagement and value of life for people living with ALS,” Neil Thakur, PhD, the ALS Association’s chief mission officer, said in a blog post.
The targeted measures — quality adjusted life years, dubbed QALYs, and equal value life years gained, or evLYG — were previously deemed inherently discriminatory against people with disabilities by the National Council on Disability. A 2019 report by the council focused on how such measures contribute to “the historical and continued devaluation of the lives of people with disabilities,” including those with ALS.
QALYs is a measure that assigns a quality score, or health utility, to a year of life lived in certain health states, with a zero representing a year in the worst health condition and a score of 1 representing a year in perfect health.
These health utilities are based on surveys that involve mainly non-disabled people. Thus, critics say, the lives of people with disabilities are assigned a lower quality score and subsequently deemed less worthy of being extended.
In addition, quality of life improvements, even small ones, are incredibly valuable to people with disabilities, and this simply is not captured by QALYs, advocates say.
The second measure, evLYG, was created to address objections to the use of QALYs. It is an unweighted measure of years of life extended with a particular therapy and is used by ICER as a supplement to QALYs to assess whether there are significant differences between the two measures.
However, evLYG continues to rely on health utilities that advocates say do not account for the complexity of the preferences and experiences of people with disabilities, including those with ALS.
As such, both measures fail to capture the value of life from the perspective of a person living with ALS — and the actual benefit of a therapy that could extend life by six months — the association stated in the blog post.
“Their approach to placing a value on additional months of life gained fails to fully capture the value of additional time with your family, of being able to see a child get married or a grandchild graduate from college — the things that truly give life meaning,” Thakur stated in his blog.
In its objecting comment, the ALS Association asked ICER to detail how it will measure quality of life and assign patients to health states, as well as how that aligns with ALS patients’ perspectives on the value of their quality of life and health.
The association also asked the institute to include the cost of medical and supportive caregiving in its main analysis.
“A successful ALS treatment will extend lives, improve quality of lives, and reduce acute and supportive care costs,” the association stated in its objection comment.
“All cost savings should be included in a cost-benefit analysis of the treatment – irrespective of whether the costs are arbitrarily classified as medical or non-medical,” the ALS Association wrote.
The advocacy group said in the blog post that its mission is clear: “The Association’s engagement with ICER is part of our longstanding fight to make sure promising treatments, like AMX0035 and Oral Edaravone, are available and accessible for people with ALS as quickly as possible.”
Amylyx Pharmaceuticals’ AMX0035, given twice a day by mouth or via feeding tube, is a fixed-dose combination of tauroursodeoxycholic acid and sodium phenylbutyrate. Each compound, already in clinical use, is known to be safe and well-tolerated, and to protect nerve cells from cellular stress-induced damage.
Data from the CENTAUR Phase 2/3 clinical trial (NCT03127514) and its open-label extension study (NCT03488524) showed that AMX0035 was generally safe and significantly slowed disease progression, while reducing the risk of death by 44% in ALS patients.
AMX0035’s benefits are now being confirmed in the larger PHOENIX Phase 3 trial (NCT05021536), which is recruiting up to 600 adults with ALS; more information on contacts and the current 33 study sites can be found here.
The therapy now is under priority review in the U.S. — with a decision expected no later than June 29 — and is being reviewed in Canada and in Europe.
The oral formulation of edaravone (MT-1186), by Mitsubishi Tanabe Pharma America (MTPA), is designed to have a similar clinical profile to the company’s Radicava, an intravenous (into-the-vein) formulation of edaravone that has been approved in the U.S. for ALS since 2017.
Edaravone works by reducing oxidative stress, a form of cellular damage that is considered one of the causes of nerve cell death in ALS.
Radicava was previously shown to safely and effectively slow functional decline in ALS clinical trials. Interim results from the open-label Phase 3 trial (NCT04165824) demonstrated that treatment for six months with oral edaravone was generally well-tolerated.
An international Phase 3b trial (NCT04569084) testing the safety and efficacy of two regimens of oral edaravone against a placebo is currently enrolling up to 380 adults with ALS.
Oral edaravone is being reviewed under priority in the U.S., with a decision expected by May 12.
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