Reimbursement Recommendation

Vamorolone (Agamree)

Indication: For the treatment of Duchenne muscular dystrophy in patients 4 years of age and older

Sponsor: Kye Pharmaceuticals Inc.

Final Recommendation: Reimburse with conditions

What Is the Reimbursement Recommendation for Agamree?

Canada’s Drug Agency (CDA-AMC) recommends that Agamree be reimbursed by public drug plans for the treatment of Duchenne muscular dystrophy (DMD) in patients aged 4 years or older, if certain conditions are met.

Why Did CDA-AMC Recommend Reimbursement?

The Canadian Drug Expert Committee (CDEC) determined that, in patients with DMD, Agamree demonstrates acceptable clinical value versus prednisone; however, the clinical value compared to deflazacort is uncertain. This determination was sufficient for CDEC to recommend that Agamree be reimbursed. Given that Agamree is expected to be an alternative to prednisone or deflazacort, acceptable clinical value refers to at least comparable value versus corticosteroids.

Evidence from a clinical trial (the VBP15-004 study [N = 121]) in children with DMD aged 4 to 7 years showed that Agamree given for 24 weeks improved physical function outcomes (North Star Ambulatory Assessment [NSAA] total score, time-to-stand [TTSTAND] velocity, and 6-minute walk test [6MWT] distance) versus placebo, and that it likely has a similar effect on physical function compared to prednisone. Evidence from 1 external comparison of Agamree, prednisone, and deflazacort suggested that the 3 treatments likely provide comparable clinical benefits in pediatric patients with DMD after 48 weeks of treatment. However, there was little to no difference between vamorolone and prednisone in side effects commonly linked to steroids, including behaviour problems, weight gain, and broken bones.

Patients and clinicians identified a need for accessible treatments that preserve physical function, prevent cardiac and respiratory decline, improve survival and health-related quality of life (HRQoL), and reduce caregiver burden without the adverse effects associated with long-term corticosteroid use. Compared with placebo, Agamree may help preserve short-term physical function. However, it is uncertain whether Agamree addresses these needs better than currently available treatments. CDEC also recognized that there remains a significant unmet need in DMD because the disease is severe, existing treatments have long-term safety considerations and access limitations, and generating high-quality evidence is challenging.

Based on all of the preceding considerations, CDEC recommended that Agamree be reimbursed.

Which Patients Are Eligible for Coverage?

Agamree should only be reimbursed for patients aged 4 years or older with a genetically confirmed diagnosis of DMD, in line with the Health Canada indication.

What Are the Conditions for Reimbursement?

Agamree should only be prescribed by a specialist such as a neurologist or physiatrist with expertise in the diagnosis and management of DMD. Agamree should not be used in combination with other corticosteroids for DMD, including prednisone or deflazacort. Reimbursement should also be discontinued if the patient experiences unacceptable toxicity. Agamree should only be reimbursed if the cost of Agamree is negotiated so that it does not exceed the cost of treatment with prednisone.

Important budget impact considerations must be addressed for health systems to be able to adopt Agamree.

Review Background

• Disease background: Duchenne muscular dystrophy (DMD) is a rare, inherited, progressive disease that most often shows symptoms in males. In early childhood, males with DMD display signs of muscle weakness, growth and motor delays, and decreased endurance, often requiring assistance with walking and breathing into early adolescence, and they continue to develop heart problems and brittle bones over time. As patients lose motor function and independence, they need to rely on their families and caregivers for everyday activities. DMD is associated with shortened life expectancy, and few males survive into their fourth decade of life. In 2012, the prevalence of DMD in males in Canada was estimated to be 6.1 per 100,000.

• Indication and reimbursement request: Vamorolone (Agamree) has been approved by Health Canada for the treatment of DMD in patients aged 4 years or older. The sponsor is seeking reimbursement for this patient population.

• Drug under review: Vamorolone is a glucocorticoid. It is available as a 40 mg/mL suspension, administered orally, and the dosage recommended in the product monograph is 6 mg/kg taken orally once daily, up to a maximum daily dosage of 240 mg for patients weighing more than 40 kg. The daily dose may be down-titrated to 4 mg/kg/day or 2 mg/kg/day based on individual tolerability, and patients should be maintained at the highest tolerated dose within the dose range.

• Treatment costs: At the submitted price of $6,000.00 per 100 mL bottle, the annual cost of vamorolone is expected to be $131,400 per patient for those weighing 40 kg or more, based on the Health Canada–recommended dosage.

Highlights of Input From Interested Parties

The patient group (Muscular Dystrophy Canada in collaboration with Defeat Duchenne Canada) noted the following regarding impacts of the disease, unmet needs, and important outcomes:

• DMD profoundly disrupts the lives of patients, families, and caregivers due to the progressive loss of motor function and independence, increased need for supportive care, increased financial burden, and psychological impact of the disease from a young age.

• Families emphasized the need for treatment that preserves ambulation and strength, prevents cardiac and respiratory decline, and improves health-related quality of life (HRQoL) without the harms associated with steroids.

The clinician group (the Neuromuscular Disease Network for Canada) and the clinical experts consulted by Canada’s Drug Agency (CDA-AMC) noted the following regarding unmet needs arising from the disease and place in therapy for the drug under review:

• In addition to what was outlined by the patient group, there is a need for treatments that are better tolerated, prolong life, and reduce caregiver burden. There is also a need for therapies that offer curative potential by restoring dystrophin, rather than being disease-modifying.

• Vamorolone is another disease-modifying option and is expected to be used as a first-line or later-line treatment for patients switching from prednisone or deflazacort.

The participating public drug programs raised potential implementation issues related to considerations for initiation, renewal, discontinuation, and prescribing of therapy; generalizability of trial populations to broader populations; and system and economic issues.

Person With Lived Experience

A person with lived experience from Ontario shared his journey living with DMD and answered questions from committee members. Diagnosed in early childhood, he described a lifelong pattern of complex medical care, including long-term steroid use, cardiac medications, bone-strengthening treatments, hormone therapy, and frequent monitoring. He emphasized the cumulative burden of treatment side effects, particularly delayed puberty, bone fragility, and the physical and emotional impacts of maturing later than his peers. Participation in multiple clinical trials over many years required significant travel and time away from school and university, yet disease progression continues due to the lack of Duchenne-specific therapies in Canada. He highlighted challenges accessing and affording current steroid treatment, which is not consistently available or publicly funded. As an adult living independently, he stressed the importance of treatments that slow muscle loss and preserve everyday functions such as using a computer, preparing meals, and travelling independently. He underscored that access to effective therapies for adults is essential, noting that “time is muscle” and that delays in access result in irreversible loss of strength.

Disclaimer: The perspectives shared by people with lived experience who present to the committee reflect their individual experiences and are not necessarily representative of all people with the same condition or course of treatment. Their insights provide valuable context about what a patient, support person, or caregiver might go through with this condition or treatment, helping to inform the committee’s deliberations. These narratives complement other forms of evidence and input and should be considered as 1 element contributing to a broader understanding of the condition and treatment under review.

Recommendation

With a vote of 12 in favour to 1 against, CDEC recommends that vamorolone be reimbursed for the treatment of DMD in patients aged 4 years or older, only if the conditions listed in Table 1 are met.

Table 1: Reimbursement Conditions and Reasons

AE = adverse event; CDA-AMC = Canada's Drug Agency; CDEC = Canadian Drug Expert Committee; DMD = Duchenne muscular dystrophy.

Rationale for the Recommendation

Clinical Value

Based on the totality of the presented clinical evidence, CDEC concluded that vamorolone demonstrates acceptable clinical value compared with appropriate comparators (prednisone or deflazacort) in pediatric patients with DMD. Given that vamorolone is expected to be an alternative to prednisone or deflazacort, acceptable clinical value refers to comparable value versus prednisone; however, the clinical value compared to deflazacort is uncertain.

Evidence from 2 studies — one 24-week, phase IIb, double-blind randomized controlled trial (RCT) (the VBP15-004 study; N = 121) evaluating the efficacy and safety of vamorolone versus placebo and prednisone in ambulatory males aged 4 to less than 7 years with a confirmed diagnosis of DMD who were not previously treated with corticosteroids; and one 12-week, phase II, open-label, multiple-dose study (the VBP15-006 study; N = 54) evaluating the safety and efficacy of vamorolone in males aged 2 to 3 years or 7 to 17 years with a confirmed diagnosis of DMD who were either previously treated or untreated with steroids — was discussed by CDEC. In the pivotal VBP15-004 study, 24 weeks of treatment with vamorolone demonstrated a clinically meaningful improvement in physical function outcomes (North Star Ambulatory Assessment [NSAA] total score, time-to-stand [TTSTAND] velocity, and 6-minute walk test [6MWT] distance) compared to placebo in children with DMD. When compared to prednisone, 24 weeks of treatment with vamorolone likely results in comparable clinical benefit in these outcomes. CDEC noted that there was little to no difference in important steroid-associated harms between vamorolone and prednisone including behaviour problems, weight gain, and fracture risk. However, CDEC also noted that there was considerable uncertainty in the magnitude and extent of benefit regarding the long-term efficacy and safety of vamorolone compared to current corticosteroid options, given the short duration of the studies.

Comparative clinical evidence versus deflazacort from 1 propensity score–matched analysis comparing vamorolone (from the VBP15-004 study) with external comparisons of prednisone and deflazacort (from the FOR-DMD study) was discussed; however, there were important limitations in the study design, heterogeneity between studies, and serious imprecision preventing definitive conclusions on the comparative effectiveness and safety of vamorolone relative to deflazacort. CDEC also noted that deflazacort is available only through Health Canada’s Special Access Program, which introduces uncertainty regarding its routine availability in clinical practice.

Input from patients, families, and clinicians identified the need for treatment that preserves physical function, prevents cardiac and respiratory decline, improves HRQoL without steroid-associated harm, prolongs life, and reduces caregiver burden. CDEC concluded that treatment with vamorolone met some of the needs identified when compared to placebo, including preserving short-term physical function; however, CDEC was unable to ascertain whether vamorolone meets the unmet needs identified when compared to currently available active treatments.

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 vamorolone. As part of the deliberation on whether to recommend reimbursement, 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 vamorolone 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.

The sponsor requested a reconsideration of the initial draft recommendation to reimburse vamorolone with conditions for the treatment of DMD in patients aged 4 years or older. There were 4 issues outlined by the sponsor in the request for reconsideration that were discussed by CDEC. Specifically, the sponsor requested that CDEC:

• reconsider the harms profile of vamorolone relative to prednisone and deflazacort from the pivotal VBP15-004 study

• consider new evidence from 1 propensity score–matched external comparison of the vamorolone clinical development program compared to classic corticosteroid data from the FOR-DMD study, Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study, and Phung et al. (2024) study

• consider new evidence from the propensity score–matched external comparison evaluating muscle function and bone health from the VBP15-LTE and FOR-DMD studies

• consider the long-term data from the VBP15-006 Expanded Access Program (EAP).

Clinical Value

• Appropriate comparators: Although prednisone is used off-label and deflazacort is only accessible via Health Canada’s Special Access Program, CDEC considered these therapies to be appropriate comparators for vamorolone as they are currently used for patients with DMD. CDEC discussed the place in therapy of vamorolone, noting that the mechanism of action is similar to other corticosteroids for the treatment of DMD, and would be used as an alternative first-line treatment option to prednisone or deflazacort, or as a later-line treatment for patients who switch from prednisone or deflazacort.

• Efficacy versus placebo: CDEC discussed the pivotal evidence submitted for this review, which consisted of 1 phase IIb RCT (the VBP15-004 study; N = 121) evaluating the efficacy and safety of vamorolone compared to placebo and prednisone. The VBP15-004 study demonstrated that treatment with vamorolone for up to 24 weeks resulted in a clinically meaningful improvement in motor function as measured by the least squares mean difference (LSMD) in NSAA total score (LSMD = 3.57 points; 95% confidence interval [CI], 1.90 to 5.25 points), TTSTAND velocity (LSMD = 0.06 rises/second; 95% CI, 0.02 to 0.10 rises/second; P = 0.0018), and 6MWT distance (LSMD = 41.59 m; 95% CI, 14.23 m to 68.94 m; P = 0.0033) compared with placebo.

• Efficacy versus prednisone: In the VBP15-004 study, at 24 weeks, treatment with vamorolone resulted in little to no difference in mobility and physical function outcomes as measured by the NSAA total score (LSMD = –1.44 points; 95% CI, –3.09 to 0.20 points), TTSTAND velocity (LSMD = –0.02 rises/second; 95% CI, –0.06 to 0.02 rises/second), and 6MWT distance (LSMD = –19.89 m; 95% CI, –45.93 m to 6.15 m) compared with prednisone. CDEC highlighted limitations of the analysis; namely, the hierarchical statistical testing procedure of the VBP15-004 study failed and comparisons between vamorolone and prednisone were not controlled for multiplicity. Additionally, CDEC emphasized the short duration of the study, for which only 24 weeks of comparative data were available, which is insufficient in a chronic, progressive disease requiring lifelong treatment.

• Efficacy versus deflazacort: CDEC noted that only 1 active comparator available in Canada (i.e., prednisone) was assessed in the clinical trial evidence for vamorolone. CDEC discussed the results of a propensity score–matched analysis comparing vamorolone from the VBP15-004 study to an external control of prednisone and deflazacort from the FOR-DMD study for up to 48 weeks. Results for the comparison between vamorolone and prednisone were consistent with the VBP15-004 study. In the comparison between vamorolone and deflazacort, there was no difference detected between treatments for outcomes of change from baseline in NSAA total score (–1.78 points; 95% CI, –3.50 to –0.06 points), TTSTAND velocity (0 rises/second; 95% CI, –0.03 to 0.03 rises/second), or 6MWT distance (5.58 m; 95% CI, –18.86 m to 30.02 m). CDEC noted the limitations with the analysis, including the heterogeneity across trials and potential for prognostic imbalances, residual confounding, small sample size following the matching procedure, and lack of design to test for noninferiority between treatments, which resulted in substantial imprecision and precluded CDEC from drawing conclusions on the comparative efficacy versus deflazacort. CDEC noted that, according to the clinical experts consulted for this review, most patients with DMD in Canada are currently receiving treatment with deflazacort, and the efficacy of vamorolone in patients who had previously received deflazacort is unknown.

• Additional evidence and longer-term efficacy and safety: CDEC noted that, in the VBP15-004 study, patients who were randomized to placebo or prednisone for the first 24 weeks of the study switched to vamorolone for the remaining 24 weeks of the study. Results for patients who switched from prednisone to vamorolone were numerically similar, suggesting that the treatment effect was maintained after switching. CDEC also discussed an open-label, long-term extension study (the VBP15-LTE study; N = 46) that evaluated the efficacy and safety of a range of vamorolone doses (i.e., 0.25 mg/kg, 0.75 mg/kg, 2 mg/kg, and 6 mg/kg) for up to 30 months of treatment in patients aged 4 to 6 years with a confirmed diagnosis of DMD, and who did not have experience with oral glucocorticoids or other immunosuppressive drugs. The potential benefits and harms of longer-term use of vamorolone in these patients appeared to be maintained for the duration of the study; however, the limitations due to small sample size, pooling of results for different doses, and lack of comparator group resulted in significant uncertainty that prevented CDEC from making conclusions about the long-term efficacy and safety of vamorolone.

• Evidence submitted for the reconsideration: During the reconsideration meeting, CDEC reviewed new evidence submitted by the sponsor, including 5 years of follow-up data for vamorolone compared with a pooled cohort of patients treated with prednisone and deflazacort. The committee noted that findings were generally consistent across the newly submitted studies and aligned with the evidence reviewed in the original submission for several efficacy and safety outcomes. These included a consistent signal favouring vamorolone for bone biomarkers and linear growth, consistent findings of increased weight gain, and no apparent difference in time to loss of ambulation. The longer follow-up period provided additional confidence in the durability of these observations. However, CDEC emphasized the substantial limitations of the propensity score–matched analyses, including important clinical and methodological heterogeneity across studies, small sample sizes, and residual imbalances in key prognostic factors despite matching and weighting. The committee also noted uncertainty regarding the comparative efficacy and safety of prednisone and deflazacort and considered it inappropriate to pool these treatments, as it may obscure important differences in their safety profiles (e.g., deflazacort may be associated with greater linear growth suppression and greater risk of fractures). Although the direction of effect generally favoured vamorolone, CDEC concluded that these limitations precluded causal inference and that the new evidence should be considered supportive rather than confirmatory.

• Harms: An important outcome of treatment for patients with DMD, as noted by input from the patient and clinician groups, is the reduction of comorbidities associated with long-term steroid use. During the initial and reconsideration meetings, CDEC and the clinical experts consulted for this review emphasized that 1 of the primary reasons for discontinuing or reducing the dose of steroids is due to both short-term (e.g., weight gain, behaviour problems) and long-term (e.g., adrenal suppression, fracture risk) tolerability and safety concerns. Given that it is a dissociative steroid, CDEC noted that there is an expected difference in short-term and long-term side effects with vamorolone compared to classic corticosteroids. When compared with placebo, CDEC noted that treatment with vamorolone may result in an increase in behaviour changes and weight, and when compared to prednisone, vamorolone may result in a decrease in behaviour changes but an increase in weight. However, CDEC noted the uncertainty in these results due to imprecision resulting from the short study duration and low event numbers. CDEC also highlighted that changes in height from baseline to week 24 were similar between the vamorolone and placebo groups. Differences between treatments in the incidence of fractures were uncertain due to low event rates and short study duration. During the reconsideration meeting, CDEC upheld their initial conclusions and noted that the additional evidence consistently suggested increased weight gain with vamorolone relative to classic corticosteroids. Although there is no evidence linking weight gain to poorer clinical outcomes in patients with DMD, the committee discussed the potential implications of weight gain on mobility and physical function. This concern was supported by the absence of an observed benefit with vamorolone in delaying the time to loss of ambulation in the additional propensity score–matched analyses. With respect to fracture outcomes, the newly submitted evidence suggested numerically fewer fractures among patients treated with vamorolone than among those receiving prednisone or deflazacort. However, CDEC emphasized the considerable uncertainty associated with these findings, given the methodological limitations of the comparative analyses. The committee further noted that nearly all patients in the comparator group of the 5-year analysis received deflazacort, which may be associated with a higher fracture risk and could bias the results in favour of vamorolone. As a result, the comparative effect of vamorolone on fracture risk relative to prednisone remains uncertain.

• Clinical importance of treatment effects: Based on the input from patient and clinician groups, preservation of motor function was a key outcome that patients valued in new treatments. CDEC considered the efficacy and safety outcomes evaluated in the provided evidence to be clinically relevant. CDEC noted that, compared to placebo, treatment with vamorolone likely results in short-term improvements in physical function that are clinically meaningful when compared to the published minimal important differences for NSAA total score (2.32 points), TTSTAND velocity (0.023 rises/second), and 6MWT distance (30 m). However, when compared to prednisone (which CDEC considered the most relevant comparator) and deflazacort, there was little to no difference between treatments, and it was uncertain whether vamorolone is safer or more effective than other steroids. As such, CDEC could not conclude that vamorolone meets the identified unmet needs versus currently available active treatments. HRQoL and caregiver burden were not evaluated in the included evidence, precluding any conclusions on whether vamorolone improves quality of life or alleviates caregiver burden. Furthermore, patients and clinicians considered extended life expectancy to be important, although outcomes related to improved survival were not evaluated, and CDEC acknowledged the difficulty in assessing these outcomes during a clinical trial. During the reconsideration meeting, CDEC reviewed longer-term evidence from 2 new propensity score–matched analyses that reported outcomes related to linear growth. Although the additional evidence consistently suggested that patients treated with vamorolone maintained expected growth trajectories and experienced less growth suppression than patients treated with prednisone or deflazacort, CDEC concluded that the clinical significance of these findings remains uncertain. First, the observed growth benefits were derived primarily from nonrandomized external comparisons and open-label studies that were subject to important methodological limitations, including heterogeneity across studies, residual confounding, small sample sizes, and selection bias. Second, although preservation of height may be valued by patients and families and may reduce some of the visible manifestations of DMD, there is currently no evidence demonstrating that improvements in growth translate into improvements in HRQoL, motor function, independence, caregiver burden, or survival. Third, DMD is characterized by progressive loss of muscle strength and functional capacity, and the relationship between increased height and long-term functional outcomes remains unclear. CDEC and the clinical experts noted that increases in height without corresponding improvements in strength or physical function could potentially increase the physical demands placed on patients. Finally, despite the observed growth signal, the additional analyses did not demonstrate a corresponding improvement in patient-important outcomes such as preservation of ambulation or physical function. Consequently, while the growth findings were considered directionally favourable, the committee concluded that their overall contribution to the therapeutic value of vamorolone remains uncertain.

• Certainty of the evidence: CDEC discussed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty-of-evidence assessment of the VBP15-004 trial. CDEC noted that, compared to placebo, 24 weeks of treatment with vamorolone resulted in clinically meaningful improvements in physical function outcomes for NSAA total score, TTSTAND velocity, and 6MWT distance — with moderate, high, and low certainty, respectively — although the 95% CIs for the NSAA and 6MWT included the possibility of no clinically meaningful benefit. When compared with prednisone, the results for the same outcomes suggested little to no difference between vamorolone and prednisone, with low to moderate certainty. The estimates of treatment effect were impacted by small sample sizes and imprecision, wherein the 95% CI for each outcome included the possibility of no clinically meaningful benefit, lack of control for multiplicity for the NSAA outcomes and comparisons with prednisone, and missing outcome data for the 6MWT.

• Generalizability: The Health Canada indication for vamorolone is for patients aged 4 years or older. The VBP15-004 study enrolled 121 patients aged 4 to 7 years, while the VBP15-006 study enrolled 45 patients aged 7 to 17 years. Additional eligibility criteria of the VBP15-004 study included the ability to walk independently and no prior treatment with corticosteroids. CDEC emphasized the generalizability concerns of the available evidence, noting that there is limited evidence in patients who are nonambulatory (9 patients enrolled in the VBP15-006 study were nonambulatory), as well as patients who have received prior treatment with corticosteroids (33 patients enrolled in the VBP15-006 study were previously treated with corticosteroids). According to the clinical experts, vamorolone is expected to be similar to standard-of-care steroids used for DMD and may offer potential benefits unrelated to motor function. Therefore, the clinical experts noted that vamorolone could be used to treat patients who are aged 7 years or older, are nonambulatory, or were previously treated with steroids. CDEC and the clinical experts noted that pediatric patients who reach the age of 18 years who continue to have a favourable response to vamorolone can continue treatment into adulthood. However, CDEC noted that there is no evidence supporting the initiation of vamorolone in patients aged 18 years or older.

• Clinical value: Based on the available evidence, CDEC determined there was comparable clinical value for vamorolone versus prednisone; however, the evidence for vamorolone versus deflazacort was too uncertain to make conclusions on clinical value. The additional long-term evidence reviewed during the reconsideration meeting provided supportive information regarding growth, bone health, and other clinically relevant outcomes; however, important methodological limitations and residual uncertainty prevented definitive conclusions regarding comparative efficacy and safety. Consequently, CDEC upheld its initial conclusions regarding the clinical value of vamorolone.

Unmet Clinical Need

• Input on unmet clinical need: Patient groups, clinician groups, and clinical experts consulted by CDA-AMC identified an unmet need for additional treatments that improve overall function including mobility (e.g., ambulation and strength), prevent cardiac and respiratory decline, and improve HRQoL through greater independence and autonomy, as well as treatments that are better tolerated without the harms associated with current steroids. Clinicians added that there is a need for treatments that are curative, prolong life, and reduce caregiver burden. CDEC also discussed the need for additional treatment options, given the known short-term and long-term harms associated with chronic prednisone and deflazacort use, as well as issues with access to deflazacort.

• Severity of the disease: CDEC discussed input from patient groups indicating that DMD is a severe, debilitating, and ultimately life-threatening disease. Patient groups noted that although current treatment options have tangible benefits, they are ultimately insufficient in improving life expectancy and minimizing functional deterioration, and are associated with substantial cumulative harms due to chronic use. The clinical experts also emphasized that there is significant disease burden and treatment burden with DMD.

• Availability of treatment options: Other than vamorolone, there are currently no treatments available in Canada with a Health Canada–approved indication for DMD. Currently, treatment options for DMD include corticosteroids (prednisone or deflazacort); however, patient groups emphasized inconsistent access to deflazacort across Canada. CDEC discussed with the clinical experts that most patients in Canada receive treatment with deflazacort. CDEC recognized that deflazacort has never been approved for use in Canada and is only available through Health Canada’s Special Access Program, and that it is not always publicly reimbursed across jurisdictions. CDEC noted that the continued availability of deflazacort through the Special Access Program is uncertain due to the recent approval of vamorolone for DMD by Health Canada.

• Participation in future clinical trials: CDEC discussed feedback on the draft recommendation from patient groups, who requested that the committee acknowledge that patients who discontinue vamorolone to participate in a clinical trial should be eligible to reinitiate treatment following trial participation. The committee recognized the importance of supporting clinical research in DMD and noted that concerns regarding treatment interruptions for clinical trial enrolment are not unique to DMD and may arise across many disease areas. CDEC considered this issue during deliberations and agreed that participation in a clinical trial should not, in itself, be viewed as a reason to permanently preclude future treatment with vamorolone.

• Significant unmet clinical need: Due to challenges with evidence generation associated with the rarity of DMD and the severity of the disease, lack of accessible treatment options, and notable long-term complications associated with standard-of-care steroids, CDEC considered there to be significant unmet need as described in the recommendation framework in the Procedures for Reimbursement Reviews document.

Distinct Social and Ethical Considerations

• Input on unmet nonclinical need: CDEC discussed the need of patients and caregivers for therapies that do not add to the stress of managing complex, multidisciplinary care routines. Vamorolone is available as an oral suspension, which CDEC noted may be easier for some families to administer than tablets.

• Equity considerations: CDEC noted geographic inequities, whereby patients in rural areas may require additional travel to specialized clinics; however, CDEC was unable to determine how vamorolone could address any health equity concerns in DMD compared to other treatment options.

• CDEC considered the unmet nonclinical needs and health inequities for patients with DMD and determined that these are not necessarily addressed by vamorolone.

Economic Considerations

• Health impacts of vamorolone versus relevant comparators: Based on the submitted economic analysis, vamorolone is predicted to be associated with a minimal gain of 0.02 life-years compared to prednisone and may result in a gain of 1.59 quality-adjusted life-years (QALYs) compared to prednisone.

• Cost of vamorolone versus relevant comparators: Based on the submitted economic analysis, vamorolone is predicted to be associated with higher costs to the health care system than prednisone (incremental costs = $1,312,264), primarily driven by increased costs associated with drug acquisition costs of vamorolone.

• Key findings of the economic evaluation: Using the sponsor’s cost-utility analysis, the CDA-AMC base-case analysis estimated that the incremental cost-effectiveness ratio for vamorolone in patients aged 4 years or older with DMD was $825,194 per QALY gained when compared with prednisone. However, CDEC noted that the comparative evidence for vamorolone versus prednisone informing this analysis was uncertain and limited the reliability of this finding.

• Certainty of the evidence: There remains considerable uncertainty in the long-term discontinuation and safety data for vamorolone. The benefit for vamorolone predicted in the CDA-AMC base-case is highly uncertain, given that it is unknown whether vamorolone will result in improvements in discontinuation and patient-important outcomes (such as steroid-associated harms like fractures, stunted growth, and cataracts). As such, CDEC noted that the evidence submitted was insufficient to determine that the total cost of vamorolone to the health system should exceed that of prednisone.

• Other considerations: The pharmacoeconomic report focused on relative effects versus prednisone, but noted that vamorolone was expected to have similar efficacy and safety relative to deflazacort and that vamorolone was associated with higher drug costs compared to deflazacort.

Impacts on Health Systems

• Anticipated budget impact: CDA-AMC estimated that by year 3 of reimbursement, 828 patients would be eligible for vamorolone; of these, 331 patients are expected to receive vamorolone. The estimated incremental budget impact of reimbursing vamorolone is predicted to be approximately $93.3 million over the first 3 years, with an expected expenditure of $93.4 million on vamorolone. The incremental budget impact of reimbursing vamorolone is predicted to be approximately $40 million in year 3, and the economic feasibility of adoption must be addressed. The actual budget impact of reimbursing vamorolone will depend on the market uptake of vamorolone, the number of patients eligible for treatment, and the reimbursement of deflazacort.

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):

• the CDA-AMC review of the clinical and pharmacoeconomic evidence submitted by the sponsor, as well as relevant ethical issues related to vamorolone (refer the Main Report and Supplemental Material document)

• the sponsor’s comments on the draft report and the CDA-AMC responses

• patients' perspectives gathered by 1 patient group, Muscular Dystrophy Canada in collaboration with Defeat Duchenne Canada (refer to the Patient and Clinician Group Input document)

• input from a person with lived experience who delivered a brief presentation and answered questions from the committee (refer to the Person with Lived Experience section earlier in this document)

• input from 1 clinician group, the Neuromuscular Disease Network for Canada (refer to the Patient and Clinician Group Input document)

• input from public drug programs that participate in the Reimbursement Review process (refer to the Supplemental Material document)

• input from 3 clinical experts with expertise in the management of DMD consulted by CDA-AMC.

Special thanks: CDA-AMC extends our special thanks to the individual who presented directly to CDEC and the patient organizations supporting the community of those living with DMD, including Muscular Dystrophy Canada and Defeat Duchenne Canada, which include Eric Morden, Darlene Morden, Homira Osman, and Nicola Worsfold.

General note: CDA-AMC makes every attempt to engage with people with lived experience as closely to the indication under review as possible; however, at times, CDA-AMC is unable to do so and instead engages with individuals with similar treatment journeys to ensure lived experience perspectives are included and considered in Reimbursement Reviews. CDA-AMC is fortunate to be able to engage with individuals who are willing to share their treatment journeys with CDEC.

Request for Reconsideration

The sponsor filed a request for reconsideration of the draft recommendation for vamorolone for the treatment of DMD in patients aged 4 years or older. In their request, the sponsor identified the following issues:

• The sponsor highlighted that the harms profile of vamorolone is not adequately differentiated from prednisone and deflazacort and that there are significant short-term and long-term harms associated with available corticosteroid treatments. The sponsor noted that there was no mention of the vertebral fracture data, bone biomarker data, or lack of effect on linear growth with vamorolone from the VBP15-004 study. The sponsor requested that additional data regarding the differentiated reduction on harms of vamorolone versus prednisone be incorporated into the recommendation.

• The sponsor provided new long-term efficacy and safety data of vamorolone from the VBP15-002, VBP15-003, VBP15-LTE, VBP15-004, and GUARDIAN studies. The sponsor therefore requested that CDA-AMC and CDEC include the 5-year fracture data for vamorolone compared to deflazacort and prednisone, as well as evidence from the cataract, linear growth, and weight gain data; loss of ambulation data; and muscle function efficacy data as part of the request for reconsideration, as they address an unmet need identified by CDEC (i.e., lack of fracture data and lack of long-term efficacy and safety data with vamorolone).

• The sponsor provided new long-term efficacy and safety data of vamorolone from the comparison of the VBP15-LTE study and FOR-DMD study, and requested that CDA-AMC and CDEC consider these data as part of the reconsideration process, incorporating the new 3-year fracture, growth, and efficacy data into the recommendation and main report to address CDEC's previously identified evidence gaps regarding fracture outcomes and long-term safety with vamorolone.

• The sponsor requested that CDA-AMC and CDEC consider newly available long-term safety and growth evidence from the EAP of the VBP15-006 study and incorporate the new linear growth (and catch-up growth data from patients previously treated with deflazacort or prednisone) into the recommendation and main report to address CDEC's identified evidence gap regarding the long-term safety of vamorolone.

In the meeting to discuss the sponsor’s request for reconsideration, CDEC considered the following information:

• information submitted as part of the sponsor’s request for reconsideration

• information from the initial submission related to the issues identified by the sponsor

• new information provided by the sponsor to address an important clear gap in the evidence identified by CDEC

• feedback from 2 clinical specialists with expertise in diagnosing and treating patients with DMD

• feedback on the draft recommendation from 2 patient groups, Muscular Dystrophy Canada and Defeat Duchenne Canada

• feedback on the draft recommendation from 1 clinician group, the Neuromuscular Disease Network for Canada

• feedback on the draft recommendation from the public drug programs that participate in the Reimbursement Review process

• feedback on the draft recommendation from the sponsor.

All feedback received in response to the draft recommendation is available on the CDA-AMC project web page.

CDEC Information

Members of the Committee (Initial Meeting)

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: January 28, 2026

Regrets: Three expert committee members did not attend.

Conflicts of interest: None

Members of the Committee (Reconsideration Meeting)

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

Reconsideration Meeting date: August 26, 2026

Regrets: Three expert committee members did not attend.

Conflicts of interest: None