Drugs, Health Technologies, Health Systems

Reimbursement Recommendation

Inebilizumab (Uplizna)

Indication: As an add-on to standard therapy for the treatment of gMG in adult patients who are AChR or MuSK antibody positive

Sponsor: Amgen Canada Inc.

Final recommendation: Reimburse with conditions

Summary

What Is the Reimbursement Recommendation for Uplizna?

Canada’s Drug Agency (CDA-AMC) recommends that Uplizna (inebilizumab) be reimbursed by public drug plans as an add-on therapy for adult patients with generalized myasthenia gravis (gMG) that is AChR or MuSK antibody positive and whose symptoms persist despite conventional therapy with AChE inhibitors, corticosteroids, and/or nonsteroidal immunosuppressive therapies (NSISTs), only if certain conditions are met.

Why Did CDA-AMC Recommend Reimbursement?

The Canadian Drug Expert Committee (CDEC) determined that Uplizna demonstrates acceptable clinical value versus conventional therapy (e.g., AChE inhibitors, corticosteroids, and/or NSISTs). This determination was enough for CDEC to recommend that Uplizna be reimbursed. Given that Uplizna is expected to be an additive treatment to conventional therapy, acceptable clinical value refers to added value versus conventional therapy.

Evidence from 1 pivotal phase III randomized, double-blind, placebo-controlled trial demonstrated that treatment with Uplizna over 26 weeks likely results in improvements in daily function and disease severity compared to placebo in the overall population of patients with gMG. CDEC discussed that Uplizna offers a different mechanism of action as a Health Canada–approved B-cell–depleting therapy compared with other available funded advanced biologics, and it may address significant unmet clinical needs. There is added clinical value for patients with gMG, particularly for the subpopulation with MuSK antibody–positive gMG that has limited treatment options and for patients whose disease remains refractory despite available treatment.

Which Patients Are Eligible for Coverage?

Uplizna should only be reimbursed for adult patients with gMG who meet all the following conditions: positive serologic test results for anti-AChR or anti-MuSK antibodies, Myasthenia Gravis Activities of Daily Living (MG-ADL) scores at baseline of 6 or higher (measured by the treating physician), Myasthenia Gravis Foundation of America class II to IV disease, and persistent symptoms despite stable doses of conventional therapy with AChE inhibitors, corticosteroids, and/or NSISTs.

What Are the Conditions for Reimbursement?

Reimbursement of Uplizna should be continued if there is documented improvement in disease symptoms, indicated by a reduction in MG-ADL score of 2 points or more following an initial 12 months of treatment or if there is proof of no worsening in MG‑ADL score provided annually for subsequent renewals. Uplizna should be prescribed by or in consultation with a neurologist with expertise in managing patients with gMG. The drug program cost of inebilizumab should be negotiated so that it does not exceed the drug program cost of treatment with the least costly advanced treatment reimbursed for the treatment of gMG.

Review Background

Highlights of Input From Interested Parties

The patient groups (Muscular Dystrophy Canada and the Sumaira Foundation) noted the following regarding impacts of the disease, unmet needs, and important outcomes:

The clinician group (the Neuromuscular Disease Network for Canada) and the clinical experts consulted by CDA-AMC noted the following regarding unmet needs arising from the disease and the place in therapy for inebilizumab:

Recommendation

With a vote of 14 in favour to 0 against, CDEC recommends that inebilizumab be reimbursed as add-on therapy for adult patients with gMG that is AChR or MuSK antibody positive and whose symptoms persist despite conventional therapy with AChE inhibitors, corticosteroids, and/or NSISTs, only if the conditions listed in Table 1 are met.

Table 1: Reimbursement Conditions and Reasons

Reimbursement condition

Reason

Implementation guidance

Initiation

1. Treatment with inebilizumab should be reimbursed for adult patients with gMG who meet all the following conditions:

1.1. positive serologic test results for anti-AChR or anti-MuSK antibodies

1.2. an MG-ADL score at baseline of 6 or higher; the MG-ADL score should be measured and provided by the treating physician

1.3. MGFA class II to IV disease

1.4. persistent symptoms despite stable doses of conventional therapy with AChE inhibitors, corticosteroids, and/or NSISTs.

Evidence from 1 phase III, randomized, double‑blind, placebo-controlled trial in adults with antibody-positive gMG whose disease responded inadequately to conventional therapies demonstrated that inebilizumab, when added to conventional therapies such as AChE inhibitors, corticosteroids, and/or NSISTs, likely results in improvements in daily function and disease severity at week 26 compared to placebo. The effect size in the subpopulation with AChR antibody–positive gMG was larger than that in the subpopulation with MuSK antibody–positive gMG.

Condition 1.4: Stable doses from the MINT trial are defined as 1 of the following:

  • corticosteroids only, with no dose increase within 4 weeks before randomization

  • NSIST, with continuous use for ≥ 6 months prior and no dose increase within 4 months before randomization

  • NSIST alone, or in combination with corticosteroids with continued use for ≥ 6 months prior (a combination of the 2 preceding definitions).

Note that patients with MuSK antibody–positive gMG may not be clinically suitable to receive AChE inhibitors.

CDEC noted that rituximab may be available in some jurisdictions; however, CDEC heard from the clinical experts that access to rituximab remains a barrier for some patients.

2. Treatment with inebilizumab should not be initiated in either of the following cases:

2.1. for patients during gMG exacerbation or crisis

2.2. for patients who have had thymectomy within 12 months.

The MINT trial excluded patients who had thymectomy within 12 months, and there is no evidence regarding the efficacy and safety of treatment with inebilizumab in patients with gMG exacerbation or crisis at baseline.

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Renewal

3. Reimbursement of treatment with inebilizumab for gMG should be continued if 1 of the following conditions is met:

3.1. following an initial 12 months of treatment, there is documented improvement in disease symptoms, indicated by a reduction in the MG‑ADL score of ≥ 2 points

3.2. for subsequent renewals, there is proof of no worsening of the MG-ADL score provided annually.

There is no evidence that inebilizumab should be held to a different standard than other Health Canada–approved targeted biologics currently reimbursed when considering renewal.

Inebilizumab should be renewed in a manner similar to those that apply to other targeted biologics for gMG.

Health Canada–approved biologics for gMG include FcRn antagonists (e.g., rozanolixizumab and efgartigimod alfa) and complement inhibitors (e.g., eculizumab, zilucoplan, and ravulizumab).

Note that the initial renewal at 12 months should be conducted following the completion of 3 doses of inebilizumab (2 initial doses of 300 mg administered 2 weeks apart, with the third dose given 6 months after the first infusion). The initial renewal at 12 months is to determine the eligibility for the fourth dose at 12 months.

Prescribing

4. Inebilizumab should be prescribed by or in consultation with a neurologist with expertise in managing patients with gMG.

Accurate diagnosis and follow-up of patients with gMG are important to ensure inebilizumab is appropriately prescribed for patients with gMG.

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5. Inebilizumab should not be used concomitantly with rituximab, FcRn antagonists, and/or complement inhibitors.

The MINT trial did not assess such combinations, and the efficacy and safety of combination use with other advanced therapies based on the submitted evidence are currently unknown.

Inebilizumab should not be used concomitantly with rituximab. The efficacy and safety of inebilizumab used concomitantly with FcRn antagonists or complement inhibitors are currently uncertain and require further research.

Pricing

6. The drug program cost of inebilizumab should be negotiated so that it does not exceed the drug program cost of treatment with the least costly advanced treatment reimbursed for the treatment of gMG.

Based on the committee’s assessment of the evidence, inebilizumab is expected to have similar clinical benefits and harms compared with relevant comparators. Therefore, the drug program cost of inebilizumab should be no more than the least costly advanced treatment reimbursed for gMG.

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CDEC = Canadian Drug Expert Committee; gMG = generalized myasthenia gravis; MG = myasthenia gravis; MG-ADL = Myasthenia Gravis Activities of Daily Living; MGFA = Myasthenia Gravis Foundation of America; NSIST = nonsteroidal immunosuppressive therapy.

Rationale for the Recommendation

Clinical Value

Based on the totality of the presented clinical evidence, CDEC concluded that inebilizumab demonstrates acceptable clinical value compared with appropriate comparators, including conventional therapy (e.g., AChE inhibitors, corticosteroids, and NSISTs) and advanced targeted biologics (e.g., rituximab, complement inhibitors, and FcRn antagonists), in patients with gMG. Given that inebilizumab is expected to be an additive treatment to conventional therapy, acceptable clinical value refers to added value versus conventional therapy.

Evidence from 1 pivotal phase III randomized, double-blind, placebo-controlled trial (MINT) comparing inebilizumab to placebo in adults with antibody-positive gMG demonstrated that 26 weeks of treatment with inebilizumab likely results in improvements in daily function and disease severity compared to placebo. At week 26 in the overall population, the least square (LS) mean change from baseline in MG-ADL score was −4.2 in the inebilizumab group and −2.2 in the placebo group. The adjusted between-group difference was −1.9 (95% confidence interval [CI], −2.9 to −1.0; P < 0.0001). While the effect size in the subpopulation with AChR antibody–positive gMG was larger than that in the subpopulation with MuSK antibody–positive gMG, CDEC discussed that inebilizumab offers a different mechanism of action as a Health Canada–approved B-cell–depleting therapy compared with other reimbursed biologics, which are either complement inhibitors or FcRn antagonists. This offers important clinical value for patients with gMG, particularly for the subpopulation with MuSK antibody–positive gMG, which has limited treatment options, and for patients whose disease remains refractory despite available treatments.

Evidence from 1 network meta-analysis (NMA) suggested that inebilizumab is similar to other comparator treatments for gMG in terms of efficacy, as assessed by changes from baseline in MG-ADL and Quantitative Myasthenia Gravis (QMG) test scores. The ability to draw firm conclusions from the NMA was limited by differences in patient characteristics, uncertainty in the distribution of some effect modifiers, sparse evidence networks, and the inability to assess the consistency assumption.

Further information on the committee’s discussion around clinical value is provided in the Summary of Deliberation section.

Developing the Recommendation

The determination of acceptable clinical value was sufficient for CDEC to recommend reimbursement of inebilizumab. As part of the deliberation on whether to recommend reimbursement or not, the committee also considered unmet clinical need, unmet nonclinical need, and health inequity. Information on this discussion is provided in the Unmet Clinical Need and Distinct Social and Ethical Considerations domains in the Summary of Deliberation section.

Because CDEC recommended that inebilizumab be reimbursed, the committee also deliberated on whether reimbursement conditions should be added to address important economic considerations, health system impacts, or social and ethical considerations, or to ensure clinical value is realized. The resulting reimbursement conditions, with accompanying reasons and implementation guidance, are stated in Table 1.

Summary of Deliberation

CDEC considered all domains of value of the deliberative framework before developing its recommendation: clinical value, unmet clinical need, distinct social and ethical considerations, economic considerations, and impacts on health systems. For further information on the domains of value, refer to Expert Committee Deliberation at Canada’s Drug Agency.

The committee considered the following key discussion points, organized by the 5 domains of value.

Clinical Value

Unmet Clinical Need

Distinct Social and Ethical Considerations

Economic Considerations

Impacts on Health Systems

Sources of Information Used by the Committee

To make its recommendation, the committee considered the following information (links to the full documents for the review can be found on the project web page):

CDEC Information

Members of the Committee

Dr. Peter Jamieson (Chair), Dr. Kerry Mansell (Vice‑Chair), Sally Bean, Daryl Bell, Dan Dunsky, Dr. Ran Goldman, Dr. Trudy Huyghebaert, Dr. Dennis Ko, Dr. Christine Leong, Alicia McCallum, Dr. Srinivas Murthy, Dr. Nicholas Myers, Dr. Krishnan Ramanathan, Dr. Marco Solmi, Carla Velastegui, Dr. Edward Xie, and Dr. Peter Zed.

Meeting date: July 22, 2026

Regrets: Two expert committee members did not attend.

Conflicts of interest: None