BOSTON, October 20, 2021 – The Institute for Clinical and Economic Review (
ICER) today released a Final Evidence Report assessing the comparative clinical effectiveness and value of eculizumab (Soliris®; sponsor: Alexion Pharmaceuticals) and efgartigimod (sponsors: argenx, Halozyme Therapeutics, and Zai Lab) for the treatment of generalized myasthenia gravis (gMG).
ICER’s report on these therapies was reviewed at the September 2021 public meeting of the New England CEPAC (
New England CEPAC), one of ICER’s three independent evidence appraisal committees.
“Myasthenia gravis is a serious lifelong disease with life-threatening manifestations, and conventional therapy with high-dose corticosteroids remains inadequate for most patients,” said Foluso Agboola, MBBS, MPH, ICER’s Vice President of Research. “While our review of available evidence suggests that both eculizumab and efgartigimod appear to significantly improve function and quality of life for these patients, there are uncertainties about longer-term outcomes for efgartigimod and how it will be dosed in real-world settings. Efgartigimod’s price is not yet known, but our analysis suggests that the current list price for eculizumab is far higher than the usual thresholds for cost-effectiveness. Further, it’s important to monitor these treatments’ effectiveness in minority populations to develop a complete picture of their overall efficacy.”
Voting on Clinical Effectiveness and Contextual Considerations
For adults with gMG, defined by MGFA clinical classes of II to IV for whom conventional immunosuppressive therapies have not been effective or have not been tolerated, and who are anti-AChR antibody positive:
- All panelists found that the evidence is adequate to demonstrate a net health benefit of eculizumab added to conventional therapy when compared to conventional therapy alone.
- A majority of panelists found that the evidence is adequate to demonstrate a net health benefit of efgartigimod added to conventional therapy over conventional therapy alone.
- All panelists found the evidence is not adequate to distinguish a net health benefit between eculizumab and efgartigimod.
- All panelists found the evidence is not adequate to distinguish the net health benefit of IVIG from that of eculizumab and efgartigimod.
- A majority of panelists found the evidence is not adequate to distinguish the net health benefit of rituximab from that of eculizumab and efgartigimod.
For adults with gMG, defined by MGFA clinical classes of II to IV for whom conventional immunosuppressive therapies have not been effective or have not been tolerated, and who are anti-AChR antibody negative:
- All panelists found that the evidence is not adequate to demonstrate a net health benefit of efgartigimod added to conventional therapy compared to conventional therapy alone.
During their deliberations, panel members also weighed the therapies’ other potential benefits, disadvantages, and contextual considerations. For both treatments, voting highlighted the following as particularly important for payers and other policymakers to note:
- The acuity of need for treatment based on the severity of myasthenia gravis;
- The magnitude of the lifetime impact on individual patients of myasthenia gravis;
- Patients’ ability to achieve major life goals related to education, work, or family life; and
- Caregivers’ quality of life and/or ability to achieve major life goals related to education, work, or family life.
Voting on Long-Term Value for Money
For the treatment of myasthenia gravis, ICER’s recommended health-benefit price benchmark (HBPB) ranges for adults with gMG, defined by MGFA clinical classes of II to IV for whom conventional immunosuppressive therapies have not been effective or have not been tolerated, and who are anti-AChR antibody positive are as follows:
- A majority of panelists found that eculizumab represents “low” long-term value for money. ICER’s recommended health-benefit price benchmark (HBPB) range for eculizumab is $13,200-$19,400, pricing levels that would require a 97-98% discount off the treatment’s wholesale acquisition cost (WAC) of $653,100.
- All panelists found that efgartigimod represents “low” long-term value for money at the assumed price of $418,400. ICER’s recommended health-benefit price benchmark (HBPB) range for efgartigimod is $18,300-$28,400. The price of efgartigimod is not yet known.
ICER’s HBPBs are price ranges suggesting the highest US price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.
Key Policy Recommendations for Fair Access:
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, and representatives from US payers and one of the manufacturers — convened to discuss the pricing implications and recommendations to ensure fair access. Key recommendations stemming from the roundtable discussion include:
- Payers should use step therapy based on clinical trial eligibility and/or authoritative evidence-based clinical specialty guidelines as they become available. Given the limited current evidence base for efgartigimod, payers should not require therapy with efgartigimod prior to coverage of eculizumab. However, as additional clinical evidence accumulates, it may be reasonable to require step therapy based on price.
- The price for eculizumab is extremely high and is distinctive for the amount by which it exceeds the price needed to reach traditional cost-effectiveness thresholds in the US. Eculizumab was first approved for paroxysmal nocturnal hemoglobinuria and hemolytic uremic syndrome, ultra-rare conditions with a cumulative prevalence of less than 4 per million. The population with gMG is 14-20 per 100,000, and if only 15% of this population is considered to have refractory gMG, the population now eligible for treatment with eculizumab is more than 7 times as large as when the drug was first approved, yet the price has not come down. There is no excuse for this level of pricing, and it should not be used as a benchmark or standard for future therapies in this clinical area or others.
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Prior to the FDA regulatory decision on efgartigimod it is not known whether the label will include all patients with gMG or whether it will be limited to patients with positive AChR antibodies. Coverage for treatment of antibody-negative patients would create a difficult choice for payers given that clinical trial data provided by the company on this relatively small subpopulation are “exploratory” and did not provide evidence of clinically significant benefits. Clinical experts advised that given the undoubted efficacy of plasmapheresis in patients with AChR negative gMG, and considering that efgartigimod has a functionally similar mechanism of action, that efgartigimod would be an appropriate therapy for select patients who have failed other therapies. Pending further data, payers deciding to limit coverage to the AChR-positive population should therefore ensure rapid consideration of exceptions through peer-to-peer conversation.
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.
