— Majority of independent appraisal committee voted that evidence is adequate to demonstrate that both AMX0035 and oral edaravone (in population narrower than its label) provide a net health benefit compared to standard of care; also determined that at current pricing or price estimates both therapies represent a “low” long-term value for money —

AMX0035 would only achieve common thresholds for cost-effectiveness if priced between $9,100 – $30,700 per year; oral edaravone far exceeds cost-effectiveness thresholds at its market price of $171,000 per year —

Given the rapidly progressive and terminal nature of the disease, clinical experts in the Policy Roundtable felt strongly that combining ALS medications that target different potential mechanisms of action is the best way to slow loss of motor neurons—

BOSTON, September 13, 2022 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report assessing the comparative clinical effectiveness and value of AMX0035 (Amylyx Pharmaceuticals, Inc.) and oral edaravone (Mitsubishi Tanabe Pharma Development America, Inc.) for the treatment of amyotrophic lateral sclerosis (ALS).

ICER’s report on these therapies was reviewed at the August 2022 public meeting of the Midwest CEPAC (Midwest CEPAC), one of ICER’s three independent evidence appraisal committees.

“The votes of the Midwest CEPAC reflected the remaining uncertainties around the benefits of these therapies and the overwhelming certainty that $170,000 per year is much too high a price for either therapy despite the overwhelming need for treatments for this devastating disease,” said David Rind, MD ICER’s Chief Medical Officer. “The evidence suggests that AMX0035 extends life, and it is clear that oral edaravone is far less burdensome than its infused preparation, but prices need to be greatly reduced to align with benefits.”

Voting on Clinical Effectiveness and Contextual Considerations

  • A majority of panelists found (11-4) the evidence is adequate to demonstrate a net health benefit when AMX0035 plus standard of care is compared to standard of care alone.

For adults with ALS who meet the narrow Study 19 criteria:

  • A majority of panelists found (13-2) that the evidence is adequate to demonstrate a net health benefit when oral edaravone plus standard of care is compared to standard of care alone.

For adults with ALS who do not meet the narrow Study 19 criteria:

  • A majority of panelists found (13-2) that the evidence is not adequate to demonstrate a net health benefit when oral edaravone plus standard of care is compared to standard of care alone.

During their deliberations, panel members also weighed the therapy’s other potential benefits, disadvantages, and contextual considerations. Voting highlighted the following as particularly important for payers and other policymakers to note:

  • Acuity of need for treatment of individual patients based on short-term risk of death or progression to permanent disability;

  • Magnitude of the lifetime impact of ALS on individuals;

  • Patients’ ability to achieve major life goals related to education, work, or family life;
  • Caregivers’ quality of life and/or ability to achieve major life goals related to education, work, or family life;

  • Patients’ ability to manage and sustain treatment with oral edaravone given the complexity of treatment with IV edaravone.


Voting on Long-Term Value for Money

AMX0035 is not yet approved by the FDA, and its manufacturer has not yet announced what the treatment’s US price will be if approved. ICER’s health-benefit price benchmark (HBPB) range for AMX0035 is between $9,100 – $30,700 per year. If priced similarly to IV edaravone at approximately $169,000 per year, the incremental cost effectiveness of AMX0035 based on the clinical data available to date would far exceed typical cost-effectiveness thresholds.

The incremental cost effectiveness of oral edaravone at an annual price of $171,000 per year far exceeds typical cost-effectiveness thresholds across multiple analyses. ICER’s health-benefit price benchmark range for oral edaravone is between $1,400 – $3,200 per year.

After reviewing the clinical evidence and considering the treatments’ other potential benefits, disadvantages, and contextual considerations noted above, the Midwest CEPAC evaluated the long-term value both therapies at current pricing (edaravone) and pricing estimates (AMX0035):

  • A majority (13-2) of panelists found that AMX0035 represents “low” long-term value for money.   
  • A majority (14-1) of panelists found that oral edaravone represents “low” long-term value for money.

Key Policy Recommendations:

ICER’s independent assessment of value informs the critical decisions that stakeholders across the US health system need to make around pricing and coverage. Following the voting session, a policy roundtable of experts — including clinical experts, patient advocates, representatives from US payers, and one pharmaceutical manufacturer — convened to discuss the pricing implications and recommendations to ensure fair access.  Key recommendations stemming from the roundtable discussion include:

  • For conditions that are rapidly progressive and fatal, considering FDA approval of drugs on the basis of a single trial that shows benefit in clinically meaningful patient-centered outcomes is not unreasonable. However, there are known risks to approving drugs on the basis of such limited evidence, and if the FDA wishes to follow this course with AMX0035 and other drugs in similar circumstances, it should be more formal in creating a specific, well-defined pathway for conditional approval.

  • Manufacturers should seek to set prices of new medications that will foster affordability and access for all patients by aligning prices with the patient-centered therapeutic value of their treatments, and not based on the price of existing ALS medications. This is especially important for ALS since new drugs are anticipated to be used in combination with other very expensive drugs, creating the highest risk for financial toxicity due to health care costs.

  • Manufacturers should consider moderating launch pricing in the context of significant uncertainty that will be addressed by clinical trials that are ongoing. One specific approach to consider is to set the launch price at a far lower price close to the cost of production until the benefits of treatment can be adequately evaluated.

  • Clinical experts confirmed that there is no clinical rationale to justify requiring step therapy through riluzole and/or edaravone before gaining coverage for AMX0035.  Mechanisms of action are complementary, side effects are very limited, and the clinical trial permitted background therapy of other FDA-approved therapies (riluzole and edaravone). Given the rapidly progressive and terminal nature of the disease, clinical experts felt strongly that combining ALS medications that target different potential mechanisms of action is the best way to slow loss of motor neurons.

ICER’s detailed set of policy recommendations, including comprehensive considerations for establishing evidence-based prior authorization criteria, is available in the Final Evidence Report and in the standalone Policy Recommendations document.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.