Reimbursement Recommendation

Bimekizumab (Bimzelx)

Indication: For the treatment of adult patients with moderate to severe hidradenitis suppurativa with an inadequate response to conventional systemic therapy

Sponsor: UCB Canada Inc.

Final recommendation: Reimburse with conditions

What Is the Reimbursement Recommendation for Bimzelx?

The Canada’s Drug Agency (CDA-AMC) Canadian Drug Expert Committee (CDEC) recommends that Bimzelx be reimbursed by public drug plans for the treatment of adult patients with moderate to severe hidradenitis suppurativa (HS) with an inadequate response to conventional systemic therapy for HS only if certain conditions are met.

Which Patients Are Eligible for Coverage?

Bimzelx should only be covered to treat patients who have moderate to severe HS (Hurley stage II or III), a total abscess and nodule count of 5 or greater, lesions in at least 2 separate areas of the body, and whose HS did not adequately respond to conventional therapy.

What Are the Conditions for Reimbursement?

Bimzelx should only be reimbursed if prescribed by a physician experienced in the management of HS and should not be reimbursed if used in combination with other biologic therapies for HS. Bimzelx should be reimbursed for ongoing treatment if there is improvement in HS after starting treatment with Bimzelx. The price of Bimzelx should be negotiated so that its total drug cost does not exceed the total drug cost of treatment with the lowest-cost adalimumab.

Why Did CDA-AMC Make This Recommendation?

• Evidence from 2 clinical trials demonstrated that treatment with Bimzelx reduced HS severity and improved HS symptoms after 16 weeks of treatment compared with placebo.

• The magnitude of benefit of Bimzelx compared to secukinumab and adalimumab after week 12 to 16 weeks and after week 48 to 52 weeks of treatment was uncertain based on evidence from 1 network meta-analysis and a matching-adjusted indirect comparison (MAIC).

• Bimzelx may meet some of the needs identified by patients, including a safe and effective treatment that controls disease and manages HS symptoms. Patients also identified the need for treatments that lead to disease remission and improve quality of life, but the evidence that Bimzelx addresses these needs was uncertain.

• Based on the CDA-AMC assessment of the health economic evidence, Bimzelx does not represent good value to the health care system at the public list price. The committee determined there is not enough evidence to justify a greater cost for Bimzelx than adalimumab over the duration of treatment.

• Based on public list prices, Bimzelx is estimated to cost the public drug plans approximately $137 million over the next 3 years; however, the actual budget impact is uncertain.

Additional Information

What Is HS?

HS is a skin condition characterized by abscesses that lead to tissue destruction and scarring on the skin. Key HS symptoms are pain, itch, malodourous discharge, burning sensations, and local warmth. The estimated prevalence of HS in North America and Europe is approximately 1% of the population.

Unmet Needs in HS

Patients identified the need for safe and effective treatments that control HS through reduction in lesions, nodules, or draining tunnels; can reduce inflammation and manage symptoms such as pain; and improve day-to-day living.

How Much Does Bimzelx Cost?

Treatment with Bimzelx is expected to cost approximately $42,366 per patient per year ($55,366 per patient in the initial year of treatment).

Recommendation

CDEC recommends that bimekizumab be reimbursed for the treatment of adult patients with moderate to severe HS with an inadequate response to conventional systemic therapy only if the conditions listed in Table 1 are met.

Rationale for the Recommendation

Evidence from 2 phase III, double-blind, randomized controlled trials (RCTs), BE HEARD I (N = 505) and BE HEARD II (N = 509), demonstrated that treatment with bimekizumab resulted in added clinical benefit compared to placebo for adult patients living with moderate to severe HS. Based on the BE HEARD trials, bimekizumab 320 mg every 2 weeks likely resulted in a clinically meaningful improvement based on the proportion of patients with at least a 50% decrease in abscesses and inflammatory nodules (AN) count with no increase in the number of abscesses and/or draining tunnels, according to Hidradenitis Suppurativa Clinical Response 50 (HiSCR50), after 16 weeks of treatment relative to placebo. Health-related quality of life (HRQoL) (based on the Dermatology Life Quality Index [DLQI] total score) and worst skin pain (based on the Hidradenitis Suppurativa Symptom Daily Diary [HSSDD] worst skin pain score response) at 16 weeks were secondary outcomes that favoured bimekizumab when compared to placebo in the BE HEARD I trial; however, the between-group difference was not considered clinically meaningful. Similar results were reported in the BE HEARD II trial, but the outcomes were tested following a prior hierarchical failure. In the absence of direct comparative evidence between bimekizumab and other biologics for the treatment of adults with moderate to severe HS, the sponsor provided indirect evidence that assessed efficacy at 12 to 16 weeks and 48 to 52 weeks relative to adalimumab and secukinumab. The indirect evidence suggested that bimekizumab may offer an advantage over secukinumab based on HiSCR50, although the magnitude of benefit is uncertain. Further, the results of the indirect evidence had no clear indication of a difference between bimekizumab and adalimumab, and no comparative safety data have been reported for bimekizumab relative to other advanced therapies.

Patient and clinician input described the considerable negative impact living with HS has on a patient’s mental and physical health, as well as social interactions, ability to carry out activities of daily living, intimacy, and work performance. Patient groups identified the following unmet needs in the treatment of patients living with HS: a safe and effective treatment that controls HS through a reduction in lesions, nodules, and/or draining tunnels; a treatment that can lead to disease remission and eliminate flares; a treatment that improves HRQoL; and a treatment that can manage HS symptoms (e.g., reduces pain). CDEC concluded that bimekizumab likely meets the need of offering an additional treatment option that is safe relative to placebo and effectively controls HS for patients living with moderate to severe HS.

Using the sponsor-submitted price for bimekizumab and the publicly listed price for all other drugs, bimekizumab was determined to be more costly than secukinumab and biosimilar adalimumab. Because there is insufficient evidence to suggest bimekizumab is more effective than adalimumab, the total drug cost of bimekizumab should not exceed the total drug cost of the lowest-cost adalimumab.

Table 1: Reimbursement Conditions and Reasons

AN = abscesses and inflammatory nodules; CDA-AMC = Canada’s Drug Agency; CDEC = Canadian Drug Expert Committee; HiSCR50 = Hidradenitis Suppurativa Clinical Response 50; HS = hidradenitis suppurativa.

Discussion Points

• Reconsideration request: The sponsor requested a reconsideration of the initial draft recommendation to not reimburse bimekizumab for the treatment of adult patients with moderate to severe HS with an inadequate response to conventional systemic therapy. CDEC discussed 6 issues outlined by the sponsor in the request for reconsideration. The sponsor requested that CDEC apply a consistent approach when appraising the primary efficacy end point (HiSCR50) for both bimekizumab and secukinumab, and that Hidradenitis Suppurativa Clinical Response 75 (HiSCR75), defined as at least a 75% reduction in AN count with no increase in abscess or draining tunnels count, be recognized as a clinically meaningful and relevant efficacy end point. The sponsor also asked for a complete and standardized evaluation of HRQoL outcomes and for flare events and antibiotic-handling practices to be interpreted appropriately within the clinical context of the disease. In addition, the sponsor requested that the methodological standards applied to the indirect comparison for bimekizumab align with those used in the secukinumab review, and that patient and clinician group input be fully considered in developing the bimekizumab recommendation.

• Indirect evidence: During the initial meeting, CDEC noted that adalimumab and secukinumab are both biologic treatment options for the treatment of HS that are available in Canada. Indirect evidence was submitted by the sponsor to address the lack of direct comparative evidence between bimekizumab and other biologics. The network meta-analysis (NMA) assessed outcomes at week 12 to 16 and the results favoured bimekizumab relative to secukinumab for some efficacy outcomes, such as HiSCR50 in the fixed-effects model. Due to methodological limitations of the NMA and 95% credible intervals (CrIs), the magnitude of benefit for bimekizumab versus secukinumab is uncertain. The clinical experts consulted by CDA-AMC expected that bimekizumab would perform similarly or better when compared to adalimumab based on experience in treating psoriasis. Though the point estimate for HiSCR50 favoured bimekizumab, the results of the indirect comparison of bimekizumab and adalimumab were subject to uncertainty due to imprecision resulting from the 95% CrI that includes the possibility of no difference, as well as the timing of the clinical trials and potential for differences in assessments based on evolving clinical practice. During the reconsideration meeting, noting these uncertainties, CDEC indicated that it was unclear if there was a difference between bimekizumab and adalimumab based on the results of the NMA. The NMA also reported comparisons of patients with flares (versus secukinumab only), reduction in worst skin pain, and HRQoL; however, none of the analyses at week 12 to 16 were supportive of a difference between bimekizumab and secukinumab or adalimumab based on these outcomes. The indirect evidence also did not report an analysis of safety outcomes between bimekizumab and relevant comparators.

• Consistency of assessment: During the reconsideration meeting, CDEC noted that bimekizumab was reviewed independently, consistent with standard process, and considered as a potential third advanced treatment option alongside secukinumab and adalimumab. The committee discussed ongoing uncertainty regarding whether bimekizumab meets an unmet need for a safer therapy with improved symptom relief, given the absence of direct head-to-head evidence and reliance solely on placebo-controlled trials (i.e., the BE HEARD I and II trials). Although HiSCR50 rates favoured bimekizumab over placebo, the wide confidence intervals (CIs) contributed to uncertainty about whether these results reflect consistent, clinically meaningful benefits across patients. The committee also noted limited comparative evidence beyond 16 weeks and uncertainty about whether bimekizumab would address loss of response seen with existing advanced therapies. Although pooled analyses from the BE HEARD I and BE HEARD II trials for achievement of HiSCR50 indicate that bimekizumab provide meaningful benefit relative to placebo, uncertainty remains regarding the magnitude and clinical relevance of benefit, particularly safety, relative to secukinumab.

• HiSCR75 as a clinically meaningful end point: During the reconsideration meeting, CDEC discussed HiSCR75 as a more stringent and clinically meaningful efficacy end point that is increasingly viewed as the new benchmark by clinical experts. Although fewer patients achieved HiSCR75 compared with HiSCR50, there is moderate certainty that bimekizumab increases the proportion of patients achieving this outcome relative to placebo at week 16. However, the absence of a control group during the maintenance period limits the ability to determine whether responses are sustained beyond the initial phase.

• Changes in HRQoL and pain were not clinically meaningful: During the initial meeting, CDEC noted that improvements in HRQoL and pain were identified as key outcomes of importance to patients. The change from baseline in total DLQI score and worst skin pain responder rate (based on the HSSDD) were not considered clinically meaningful. Further, these end points were tested following a prior failure in the statistical testing hierarchy in the BE HEARD II trial. Of note, the assessment of HRQoL based on DLQI score was limited by a minimal important difference (MID) that is not specific to HS and an assessment at 16 weeks that is likely too short to expect a clinically meaningful improvement. Indirect evidence also indicated no difference in HRQoL or pain between bimekizumab and secukinumab or adalimumab. During the reconsideration meeting, CDEC noted that descriptive consideration of the EQ-5D-3L visual analogue scale (VAS) could be included; however, its interpretability remains limited due to the absence of an evidence-based MID and the exploratory nature of the end point, particularly given the lack of adjustment for multiple comparisons and absence of reported between-group differences. The committee noted that DLQI score was the most clinically relevant HRQoL measure in the trials, consistent with its designation as a key ranked secondary end point. Although the DLQI score MID was achieved for bimekizumab but not for placebo at week 16, uncertainty remains regarding whether the between-group difference reflects a clinically meaningful improvement, especially given the lack of controlled comparative data beyond week 16.

• Antibiotic use: During the initial meeting, CDEC discussed the use of concomitant systemic antibiotic rescue medication that was reported in the BE HEARD trials. In the bimekizumab and placebo treatment groups, respectively, 17% and 20.8% of patients in the BE HEARD I trial, and notably, 15.1% and 8.1% of patients in the BE HEARD II trial, reported the use of systemic antibiotic rescue medication at week 16. Rescue antibiotic use increased in both treatment groups through week 48. The committee acknowledged that the antibiotic use reported was not specific to the treatment of HS, though the similar or increased use of antibiotics observed with bimekizumab relative to placebo raised concerns from the committee about the management of HS. As such, there is uncertainty about the impact that antibiotic use might have on HRQoL or long-term outcomes. During the reconsideration meeting, CDEC noted that across trials, concomitant systemic antibiotic use was similar or higher in the bimekizumab group than with placebo. While this pattern was not viewed as directly influencing the efficacy of bimekizumab, the committee noted that antibiotic exposure, regardless of whether it was HS-specific or not, carries inherent risks and it remains unclear whether the higher antibiotic use in the BE HEARD II trial reflects a potential safety signal.

• Patient and clinician group feedback on the draft recommendation: During the reconsideration meeting, CDEC reviewed feedback on the draft recommendation from patient and clinician groups. The clinician group emphasized that achievement of HiSCR50 at week 16 is a meaningful early indicator of reduced inflammation and prevention of tunnelling and drainage, and although HS often improves beyond 16 weeks, early results should not be dismissed. Clinicians highlighted that benefits were demonstrated in the BE HEARD I and II trials, arguing that CI threshold crossing should not imply the absence of a meaningful effect, particularly given that bimekizumab demonstrated efficacy at higher HiSCR thresholds (HiSCR75, HiSCSR90 [at least a 90% reduction in AN count with no increase in abscess or draining tunnels count], and HiSCR100 [a 100% reduction in AN count with no increase in abscess or draining tunnels count]), which they consider more reflective of real disease improvement and aligned with patient priorities. The clinician group also raised concerns with relying solely on DLQI score, which is not specific to HS and may underestimate quality of life impacts, and emphasized that quality of life improvements typically lag behind clinical response, making week 16 HRQoL assessment premature. Finally, the clinician group explained that antibiotic use in the trials reflects real-world HS management, as antibiotics are required during washout and for flares, and should not be interpreted as diminishing treatment effects. The patient groups in their feedback on the recommendation noted that current outcome tools (e.g., HiSCR50, DLQI) do not fully capture HS burden, particularly for patients with longstanding disease, scarring, or draining tunnels, and argued that the evidence was not interpreted consistently compared to other biologics. They stressed the need for multiple treatment options due to variability in response and raised concerns that the do not reimburse recommendation could worsen access and equity issues for patients relying on public coverage. Overall, the patient groups called for a more patient-centred interpretation of evidence that better accounts for meaningful outcomes, the complexity of HS, and the real-world burden of flares, drainage, and reliance on antibiotics, surgery, and wound care.

• Lack of long-term evidence: During the initial and reconsideration meetings, the committee discussed the lack of evidence to support whether bimekizumab would address varying response and loss of response as there is limited comparative data. More specifically, evidence beyond week 16 included both every 2 weeks and every 4 weeks administration in the maintenance treatment phase for the bimekizumab group, and included patients transitioning from placebo to bimekizumab every 2 weeks. In the absence of a comparator group for the 48-week follow-up time point, it is not possible to draw definitive conclusions about the long-term efficacy or harms of bimekizumab versus any comparator, including placebo. Moreover, there is no evidence to suggest that treatment with bimekizumab leads to disease remission, and given the chronic nature of this condition, the limited evidence beyond 48 weeks does not sufficiently assess whether bimekizumab supports long-term control of symptoms.

• Additional treatments for HS: During the initial and reconsideration meetings, CDEC discussed that clinical expert input received by CDA-AMC, as well as guidelines for practice in Canada, which indicate that additional biologics (i.e., infliximab, ustekinumab, brodalumab, risankizumab, guselkumab, and certolizumab) may be used in the treatment of moderate to severe HS. Experts noted, however, that the frequency of use of such off-label treatments varies widely by jurisdiction. The efficacy and safety, as well as the cost-effectiveness, of bimekizumab versus biologics other than secukinumab and adalimumab is unknown because of a lack of comparative clinical data.

• Budget impact: CDEC discussed the uncertainty in the estimated budget impact of reimbursing bimekizumab, owing to uncertainty in the prevalence of HS, the anticipated market uptake of bimekizumab, and the presence of confidential negotiated prices for bimekizumab, secukinumab, and adalimumab. Adalimumab and adalimumab biosimilars are listed on most public formularies and are reimbursed for HS, and secukinumab completed negotiations with the pan-Canadian Pharmaceutical Alliance in 2025 for the treatment of HS. It is therefore likely that bimekizumab, secukinumab, and adalimumab are reimbursed by jurisdictional drug plans at confidential prices that are less than the publicly available list prices.

Background

HS is a chronic, systemic, and debilitating inflammatory skin disease resulting from hair follicle occlusion, which results in a cycle of chronic inflammation, abscess formation, and inflamed nodules with draining tunnels and scarring. Symptoms of HS include pain, itch, skin damage, infection, odorous secretions, and physical and/or movement limitations, which can interfere with physical functioning, activities of daily living, and work and productivity. HS substantially impacts HRQoL, such as mental well-being and sexual dysfunction, and is also associated with comorbidities such as psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, inflammatory bowel disease, polyendocrine metabolic ovarian syndrome (previously known as polycystic ovarian syndrome), diabetes mellitus, thyroid disease, obesity, metabolic syndrome, acne, and pyoderma gangrenosum. The prevalence of HS in Canada is estimated to be up to 3.8% of the general population, based on a 2016 survey. Of patients newly diagnosed with HS, a single-centre chart review in Canada reported that 55% of patients had mild HS and 45% of patients had moderate to severe HS upon diagnosis. HS is diagnosed based on clinical presentation, without the need for any biological or pathological tests for diagnosis. The Dessau Criteria is used to diagnose HS by characterizing recurrent, painful, or suppurating nodules that are present on 2 or more occasions within 6 months.

In Canada, HS treatment guidelines recommend personalizing treatments based on patient needs and disease stage (i.e., mild [stage I], moderate [stage II], or severe [stage III] according to the Hurley system). Topical therapies (e.g., skin cleansers, resorcinol, and antibiotics) used as adjuncts may be effective in managing mild HS cases; however, conventional systemic treatments (e.g., oral antibiotics, oral retinoids, oral contraceptives, or spironolactone) should be considered for patients with mild HS that is considered refractory to topical therapies. For cases with suboptimal or inadequate response to conventional systemic treatments, patients with moderate to severe HS (Hurley stage II or III) may receive biologic therapy; for severe HS, early initiation of biologic therapy is recommended. Adalimumab and secukinumab are currently approved for HS in Canada. Other second-line biologics without approval for use in HS discussed in the Canadian guidelines for moderate to severe HS include infliximab, anakinra, and ustekinumab.

Bimekizumab has been approved by Health Canada “for the treatment of adult patients with moderate to severe hidradenitis suppurativa with an inadequate response to conventional systemic therapy.” Bimekizumab is a humanized immunoglobulin G1, kappa monoclonal antibody with 2 identical antigen binding regions that target IL-17A, IL-17F, and IL-17AF cytokines, blocking their interaction with the IL-17RA and IL-17RC receptor complex to suppress expression of inflammation-related genes. Bimzelx is available as a solution for injection and the recommended dose of for adult patients with HS is 320 mg (given as 2 subcutaneous injections of 160 mg or 1 subcutaneous injection of 320 mg) every 2 weeks up to week 16 and every 4 weeks thereafter.

Sources of Information Used by the Committee

To make its recommendation, the committee considered the following information:

• a review of 2 phase III, multicentre, randomized, double-blinded, placebo-controlled studies in adult patients (≥ 18 years) with moderate to severe HS; and 2 indirect treatment comparisons

• patients’ perspectives gathered by patient groups, the Canadian Skin Patient Alliance (CSPA) and the Hidradenitis & Me Support Group (HS & Me)

• input from the public drug plans that participate in the reimbursement review process

• input from 2 clinical specialists with expertise diagnosing and treating patients with HS

• input from 1 clinician group, the Atlantic Dermatology Specialist Group

• a review of the pharmacoeconomic model and report submitted by the sponsor

• information submitted as part of the sponsor’s request for reconsideration (described subsequently)

• feedback on the draft recommendation.

Perspectives of Patients, Clinicians, and Drug Programs

The information in this section is a summary of input provided by the patient and clinician groups that responded to the CDA-AMC call for input and from the clinical experts consulted for the purpose of this review.

Patient Input

CSPA and the HS & Me collaboratively provided input for this review. CSPA is a national charity organization aiming to improve the health and well-being of people in Canada who are affected by skin, hair, and nail conditions through collaboration, advocacy, and education. HS & Me provides a safe space for individuals with HS to connect, share experiences, and learn about the condition. Information was gathered for this input submission through patient responses from 3 surveys: The 2020 national report of patients’ experiences living with HS, The Health Policy Partnership’s 2024 Call to action: improving the lives of people with hidradenitis suppurativa (HS) in Canada, and a patient survey hosted by the patient groups from March 28 to May 23, 2023. The 2020 survey gathered responses from 537 individuals with HS, of which 14% were from Canada, 50% were from the US, and 12% were from the UK. There was representation from across Canada, with the majority of respondents from Ontario (41%) and Alberta (18%). In total, 15 responses were received from the 2023 survey, where all respondents were from Canada, and the majority were from Ontario (47%) and Alberta (27%). In addition, HS & Me gathered information through posting in a Facebook group of people in Canada with HS, requesting experiences from individuals who had received bimekizumab; 4 patients with relevant experience submitted responses.

Overall, the survey respondents indicated that HS has a profoundly negative impact on their mental and physical health, social interactions, ability to carry out activities of daily living, intimacy, and work performance. In addition to these effects, patients highlighted specific concerns, such as body odour, clothing stains, and the unpredictable nature of disease flares. All respondents to the 2023 survey noted that their HS lesions are chronic, with most constantly experiencing active lesions that persist for months. Nearly all patients reported moderate daily pain, which remains poorly controlled with existing treatments for 46% of respondents; however, the input did not provide details on which treatments respondents were receiving or referring to. Most patients (61%) expressed dissatisfaction with currently available treatment options, primarily due to side effects and long wait times, and challenging recovery processes for surgical treatment options. On average, respondents to the 2020 survey had tried 15 different medications, surgical procedures, home treatments, or lifestyle modifications to help manage symptoms, yet only a small proportion experienced considerable improvement. Although prescription treatments exist that may benefit certain patients, fewer than 35% of respondents had accessed them and many emphasized the high personal cost of wound care and treatment, which the input noted suggests access and affordability challenges.

Improved access to affordable, safe, and effective treatments with better pain management and symptom relief were identified as a top priority for patients. Primary treatment goals highlighted by patients in the 2020 national report survey included symptom control (90%), curing disease completely (71%), and the ability to enjoy personal relationships (69%). Diagnostic delays were also an important issue for respondents, noting this often results in worsened symptoms and more advanced disease progression by the time an accurate diagnosis is received.

The patient group input included experiences from 4 patients who had used bimekizumab for HS treatment. At least 2 began treatment through a clinical trial, while 1 accessed it through private insurance. Three of the 4 patients reported symptom improvement while receiving bimekizumab; however, 2 discontinued treatment due to side effects, particularly fatigue. One patient remains on the therapy, noting that they are “doing quite well on it.” The respondent who accessed bimekizumab through private insurance was on treatment for 1.5 years and reported a reduction in flare-up intensity, particularly with fewer abscesses in affected areas.

Clinician Input

Input From Clinical Experts Consulted for This Review

The clinical experts noted that current management options, adalimumab and secukinumab, can reduce pain and flares, and slow or halt disease progression. However, they noted patients experience varying responses to these treatments and many eventually plateau or lose response to treatment. While experts indicated that secukinumab was a useful addition to the treatment landscape, they noted it is often underdosed and insufficient to achieve full disease control. Conversely, experts noted that adalimumab, even when dose-escalated, demonstrates waning effectiveness over time, or may induce antidrug antibodies. The clinical experts indicated that some off-label therapies, including infliximab, show some efficacy in managing HS but are challenging to access as coverage requests are rarely, if ever, approved through special access programs. Experts also noted that off-label treatment options are also typically insufficient to fully control disease.

The clinical experts suggested that bimekizumab could be used as a first-line advanced therapeutic after trialling and failing a 3-month course of anti-inflammatory antibiotics, and eligibility should align with the criteria for adalimumab and secukinumab. One expert suggested allowing patients to initiate bimekizumab as long as they are currently undergoing a 3-month course of antibiotics, explaining that for many moderate to severe cases, it is evident early in this period that biologic therapy will be necessary afterward. Experts noted that early intervention is a key factor in managing HS and saving tissue, through stopping tunnelling and scarring. They also reported that some patients whose HS does not respond adequately to 1 biologic will have response with a different biologic, and thus noted that prior biologic treatment should not impact the ability to access another option. The clinical experts indicated that patients with moderate to severe HS or Hurley stage II to III disease would be best suited for bimekizumab treatment, especially if they also have psoriasis. Experts indicated there is not currently a method of assessing whether a patient’s HS will respond better to anti-TNF or anti–IL-17 therapy; however, some patients who are not suitable for anti-TNF therapy (e.g., they have also be diagnosed with lupus, severe cardiovascular disease, recent malignancy, or demyelinating disease) would be more suited to bimekizumab. Patients least suited to bimekizumab are those with known inflammatory bowel disease, recurrent and severe candidiasis, and hypersensitivity to the drug. The clinical experts noted that HS is most often diagnosed clinically, using Hurley staging, and is rarely misdiagnosed by dermatologists. While bedside imaging has been used by some providers, experts noted that this method is not validated or accessible to all patients.

The experts noted that measures of assessing treatment response in clinical practice largely align with that of the clinical trials. For objective outcomes, nodules and abscesses are compared before and after starting therapy, including number of lesions, ideally at least 3 to 6 months after initiation. Pain score reductions are sometimes recorded, though this is less often measured in practice. Key patient-reported outcomes indicating a positive treatment response are decreased pain and drainage, as well as a reduction in flare frequency and intensity. One clinical expert indicated that patient-reported outcomes are often more representative of treatment response as chronic scarring from lesions can preclude the ability to see lesion clearance. The clinical experts considered a clinically meaningful treatment response to be at least a 25% reduction in AN count after 3 months and/or a 50% reduction by 6 months. Experts anticipate that disease improvement will be slow for most patients, as heavily inflammatory lesions subside slowly and lifestyle factors, such as stress and dietary triggers, may cause flares. The clinical experts indicated that bimekizumab discontinuation should be considered in the event of adverse reactions, minimal to no reduction in abscesses and nodules, and no decrease in pain within the first 3 to 6 months of treatment. The clinical experts agreed that bimekizumab treatment should be initiated and managed by dermatologists with a thorough understanding of HS to ensure proper use and monitoring of biologics and effective management of potential AEs; however, there was no consensus as to whether other specialties, including general practitioners with dermatology expertise, could prescribe and monitor bimekizumab treatment.

Clinician Group Input

One clinician group, the Atlantic Dermatology Specialist Group, submitted input for this review based on contributions from 4 clinicians. The Atlantic Dermatology Specialist Group comprises dermatology-certified physicians practising general dermatology who have extensive experience in managing various skin conditions, including HS. Information was gathered for this input submission through relevant published literature and clinical disease experience.

Overall, the clinician group input was consistent with the input provided by the consulted clinical experts, though some of the feedback received varied slightly and are described herein. The clinician group noted that adalimumab and secukinumab achieve modest symptom improvement in HS but often fail to improve permanent lesion scarring, and many patients continue to experience draining, painful, scarring lesions or intolerable side effects. They also emphasized additional treatment goals, including reducing the need for surgical intervention, preventing comorbidities, and enabling patients to return to the workforce. According to the clinician group, an “ideal” HS treatment would result in 90% to 100% of patients achieving HiSCR50, with a large proportion achieving 90% to 100% reductions. Consistent with input provided by the experts consulted for this review, the clinician group anticipated that bimekizumab will be used in the first line, adding that it could be used as monotherapy or in combination with other therapies for maintenance and/or flares. The clinician group anticipates that bimekizumab will cause a shift in the current treatment paradigm, noting they have found it to be more efficacious than current treatments in clinical practice. The group also noted that bimekizumab is the first to assess and meet higher efficacy end points, such as HiSCR90 and HiSCR100. Both the clinical experts and clinician group emphasized the importance of aligning bimekizumab initiation criteria with that of other biologic treatments and not requiring patients to first try other biologic options. They advised against the use of bimekizumab in individuals under 18, those who are pregnant or breastfeeding, or in combination with other biologics due to a lack of research. For patients whose HS responds to therapy, the clinician group recommended reassessment every 12 months or as needed in the event of AEs or loss of response. They also noted that treatment discontinuation should be considered if no response is observed after 4 to 6 months or if intolerable AEs or pregnancy occur. While the experts and the clinician group agreed that bimekizumab should be initiated by practitioners with expertise in HS and biologic therapies, the clinician group added that prescription renewal could be performed by any practitioner able to assess disease severity and monitor treatment efficacy and AEs.

Drug Program Input

The clinical experts consulted for the review provided advice on the potential implementation issues raised by the drug programs.

Table 2: Responses to Questions From the Drug Programs

CDEC = Canadian Drug Expert Committee; HS = hidradenitis suppurativa.

Clinical Evidence

Two double-blinded, placebo-controlled RCTs, BE HEARD I (N = 505) and BE HEARD II (N = 509), evaluated the efficacy and safety of bimekizumab versus placebo in adults (18 and older) with moderate to severe HS for at least 6 months before the baseline visit. All patients had a history of inadequate response to systemic antibiotics for HS. The primary objective was the same in both trials: to evaluate the efficacy of bimekizumab in patients with moderate to severe HS based on an HS clinical response score reduction of 50% or more (HiSCR50) at week 16. The secondary objectives were also identical: to evaluate the efficacy of bimekizumab on other measures of disease activity, and the safety of bimekizumab, in patients with moderate to severe HS. Secondary efficacy end points were also assessed at week 16 and the measures of disease activity included the HiSCR75, absolute change from baseline in DLQI total score, absolute change in skin pain score per the HSSDD, and skin pain response based on a clinically meaningful change from baseline in the HSSDD. The BE HEARD II trial included 1 additional measure of disease activity as a secondary efficacy end point, which was the occurrence of a flare by week 16.

Both trials were completed in 3 study periods. An initial screening period, a 48-week treatment period, and a 20-week safety period for post-treatment follow-up. The treatment period comprised a double-blinded, placebo-controlled initial treatment period (week 0 to 16), followed by a double-blinded 32-week maintenance treatment period (weeks 16 to 48), during which all patients received bimekizumab. In both studies, patients were randomized (2:2:2:1) to receive either bimekizumab 320 mg every 2 weeks from weeks 0 to 48; bimekizumab 320 mg every 4 weeks from weeks 0 to 48; bimekizumab 320 mg every 2 weeks from weeks 0 to 16, continuing on bimekizumab 320 mg every 4 weeks from weeks 16 to 48; or placebo until week 16, continuing on bimekizumab 320 mg every 2 weeks from weeks 16 to 48.

The Health Canada–approved dosing is bimekizumab 320 mg every 2 weeks for the first 16 weeks, followed by bimekizumab 320 mg every 4 weeks thereafter. Within each study, data were pooled for the 2 groups that received bimekizumab 320 mg every 2 weeks during the initial treatment period, which was formally compared to the placebo group at week 16. In addition, data from the 2 groups that switched regimens for the maintenance treatment period are presented as supporting evidence from weeks 16 to 48, which includes the group that switched from placebo in the initial treatment period to bimekizumab every 2 weeks for the maintenance treatment period, and the group that switched from bimekizumab every 2 weeks in the initial treatment period to every 4 weeks for the maintenance treatment period.

Across both trials, the mean age of patients ranged from 36.4 years (standard deviation [SD] = 12.4) in the placebo group in the BE HEARD I trial to 38.1 years (SD = 13.2) in the placebo group in the BE HEARD II trial. At baseline, most patients were diagnosed with Hurley stage II (derived) disease severity, ranging from 47.2% in the placebo group (34 of 72 total patients) of the BE HEARD I trial to 60.8% in both the bimekizumab (177 of 291 patients) and placebo (45 of 74 patients) groups of the BE HEARD II trial. Mean disease duration ranged from 7.4 years in the bimekizumab group of the BE HEARD II trial to 11.5 years in the placebo group of the BE HEARD I trial. In the BE HEARD I trial, most patients across both groups were female (60.9% in the bimekizumab group and 61.1% in the placebo group), whereas in the BE HEARD II trial, 51.5% of the bimekizumab group was female versus 41.9% in the placebo group.

Efficacy Results

Input from patient groups, clinician groups, and clinical experts emphasized the need for new HS treatments that are safe, effective (i.e., reduce lesions or flares and pain), and lead to disease remission. Some key goals highlighted by the experts consulted during the review for HS management in current practice included pain reduction, minimizing drainage, prevention of new lesions or flares, and slowing or halting disease progression. In consultation with the experts, the following study outcomes assessed were determined to best represent these treatment goals and considered the most realistic based on clinical practice; therefore, they were the focus of this review.

HiSCR50 Responder Rate

The primary efficacy end point in both trials was the proportion of patients who achieved HiSCR50 at week 16 (primary end point), defined as a greater than or equal to 50% reduction from baseline in total AN count, with no increase from baseline in abscess or draining tunnel count.

BE HEARD I — The HiSCR50 responder rate (adjusted for intercurrent events and missing information imputed) at week 16 was 44.8% (95% CI, 35.8% to 53.8%) in the pooled bimekizumab 320 mg every 2 week group versus 26.7% (95% CI, 15.0% to 38.4%) in the placebo group (odds ratio [OR] = 2.23; 97.5% CI, 1.16 to 4.31; P = 0.006 [tested at alpha = 0.025]). The between-group difference was 18.15% (95% CI, 6.31% to 29.98%) in favour of bimekizumab.

BE HEARD II — The HiSCR50 responder rate (adjusted for intercurrent events and missing information imputed) at week 16 was 50.3% (95% CI, 41.5% to 59.0%) in the pooled bimekizumab 320 mg every 2 week group versus 30.7% (95% CI, 18.6% to 42.7%) in the placebo group (OR = 2.29; 97.5% CI, 1.22 to 4.29; P = 0.003 [tested at alpha = 0.025]). The between-group difference was 19.61% (95% CI, 7.5% to 31.72%) in favour of bimekizumab.

HiSCR50 responder rates at week 48 was an exploratory outcome in both studies. In the BE HEARD I trial, in the bimekizumab 320 mg every 2 weeks then every 4 weeks group, the responder rates were 40.2% (95% CI, 31.7% to 48.7%). The responder rates at week 48 in the BE HEARD II trial in the bimekizumab 320 mg every 2 weeks then every 4 weeks group were 44.5% (95% CI, 36.0% to 53.0%).

HiSCR75 Responder Rate

HiSCR75 at week 16 was assessed as a ranked secondary outcome in the BE HEARD I and II trials.

BE HEARD I — The HiSCR75 responder rate (adjusted for intercurrent events and missing information imputed) at week 16 was 35.7% (95% CI, 27.0% to 44.4%) in the pooled bimekizumab 320 mg every 2 weeks group versus 20.3% (95% CI, 9.4% to 31.2%) in the placebo group (OR = 2.18; 97.5% CI, 1.02 to 4.64; P = 0.021 [tested at alpha = 0.025]). The between-group difference was 15.35% (95% CI, 3.71% to 27.00%) in favour of bimekizumab.

BE HEARD II — The HiSCR75 responder rate (adjusted for intercurrent events and missing information imputed) at week 16 was 36.8% (95% CI, 28.4% to 45.2%) in the pooled bimekizumab 320 mg every 2 weeks group versus 16.3% (95% CI, 6.8% to 25.7%) in the placebo group (OR = 3.01; 97.5% CI, 1.37 to 6.58; P = 0.002 [tested at alpha = 0.025]). The between-group difference was 20.57% (95% CI, 9.90% to 31.26%) in favour of bimekizumab.

Responder rates for HiSCR75 up to week 48 were reported in both trials as exploratory end points.

BE HEARD I — Responder rates at week 48 were 28.1% (95% CI, 20.2% to 35.9%) in the bimekizumab 320 mg every 2 weeks then every 4 weeks group and 26.6% (95% CI, 15.9% to 37.3%) in the placebo then bimekizumab 320 mg every 2 weeks group.

BE HEARD II — Responder rates at week 48 were 32.8% (95% CI, 24.8% to 40.8%) in the bimekizumab 320 mg every 2 weeks then every 4 weeks group and 48.5% (95% CI, 36.7% to 60.4%) in the placebo then bimekizumab 320 mg every 2 weeks group.

Flare

A flare was defined as a minimum 25% increase in AN count, with an absolute increase greater than or equal to 2 ANs relative to baseline. In the BE HEARD I trial, flare rate by week 16 was analyzed descriptively as a nonranked secondary end point; in the BE HEARD II trial, flare by week 16 was tested as a ranked secondary end point but was not found to be statistically significantly different, terminating hierarchal testing. In both trials, flare by week 48 was an exploratory outcome and only presented descriptively. The clinical experts noted that because the goal in real-world practice is to reduce flares over a longer time period, flare by week 48 was considered more clinically relevant.

BE HEARD I — By week 16, 28.5% (95% CI, 23.2% to 33.9%) of patients in the pooled bimekizumab 320 mg every 2 weeks group reported a flare. By week 48, 55.9% (95% CI, 47.6% to 64.3%) of patients in the bimekizumab 320 mg every 2 weeks then every 4 weeks group reported a flare.

BE HEARD II — By week 16, 28.8% (95% CI, 23.5% to 34.1%) of patients in the pooled bimekizumab 320 mg every 2 weeks group reported a flare compared with 28.0% (95% CI, 17.6% to 38.4%) of patients in the placebo group (OR = 1.050; 97.5% CI, 0.541 to 2.041; P = 0.868 [tested at alpha = 0.025]). By week 48, 51.2% (95% CI, 42.9% to 59.4%) in the bimekizumab 320 mg every 2 weeks then every 4 weeks group reported a flare.

Change From Baseline in DLQI Total Score

Change from baseline in DLQI total score at week 16 was included as a ranked secondary outcome in both trials. An MID of 4 points was adopted by the sponsor as a clinically meaningful threshold, based on evidence from prior studies in other skin conditions (not HS).

BE HEARD I — the least squares mean change from baseline to week 16 was –5.21 (95% CI, –6.14 to –4.29) in the pooled bimekizumab 320 mg every 2 weeks group and –2.53 (95% CI, –4.07 to –0.996) in the placebo group. The between-group treatment difference was –2.68 (97.5% CI, –4.39 to –0.97; P < 0.001 [tested at alpha = 0.025]) in favour of bimekizumab.

BE HEARD II — The least squares mean change from baseline was –4.69 (95% CI, –5.49 to –3.897) in the pooled bimekizumab 320 mg every 2 weeks group versus –2.38 (95% CI, –3.64 to –1.13) in the placebo group. The between-group difference was –2.31 (97.5% CI, –3.71 to –0.91). Statistical significance could not be interpreted due to a non–statistically significant result in a prior step in the statistical testing procedure.

Change from baseline in DLQI total score was reported up to week 48 in both trials. In the bimekizumab every 2 weeks then every 4 weeks group, mean change from baseline at week 48 was –5.0 (SE = 0.6) in the BE HEARD I trial and –5.4 (SE = 0.6) in the BE HEARD II trials. In the placebo then bimekizumab every 2 weeks group, mean change from baseline was –6.1 (SE = 1.2) in the BE HEARD I trial and –6.7 (SE = 0.8) in the BE HEARD II trial.

Change From Baseline in Hidradenitis Suppurativa Quality of Life Total Score

Change from baseline in Hidradenitis Suppurativa Quality of Life (HiSQOL) total score up to week 48 was assessed as an exploratory outcome in both trials. A clinically meaningful change in HiSQOL total score was defined as a minimum 20-point reduction from baseline score.

BE HEARD I — By week 16, the mean change from baseline in HiSQOL total score was −11.1 (SE = 1.1) in the pooled bimekizumab 320 mg every 2 weeks group and −5.2 (SE = 1.6) in the placebo group. By week 48, the mean change from baseline was −12.3 (SE = 1.3) in the bimekizumab 320 mg every 2 weeks then every 4 weeks group and −13.0 (SE = 2.2) in the placebo then bimekizumab 320 mg every 2 weeks group.

BE HEARD II — By week 16, the mean change from baseline in HiSQOL total score was −10.3 (SE = 1.0) in the pooled bimekizumab 320 mg every 2 weeks group and −5.8 (SE = 1.3) in the placebo group. By week 48, the mean change from baseline was −13.4 (SE = 1.2) in the bimekizumab 320 mg every 2 weeks then every 4 weeks group and −15.6 (SE = 1.6) in the placebo then bimekizumab 320 mg every 2 weeks group.

Worst Skin Pain Responder Rate

The HSSDD is a patient-reported outcome that evaluates patient perception of the main HS symptoms over a 24-hour recall period. At week 16, HSSDD worst skin pain responder rate was assessed as a ranked secondary outcome, based on a clinically meaningful change in the worst skin pain item among study participants who had a score of 3 or more at baseline. A clinically meaningful change for the HSSDD worst skin pain was defined as a minimum 3-point reduction from baseline score, based on weekly averages.

BE HEARD I — The adjusted responder rate was 35.4% (95% CI, 24.1% to 46.6%) in the pooled bimekizumab 320 mg every 2 weeks group versus 16.7% (95% CI, 3.6% to 29.8%) in the placebo group (OR = 2.76; 97.5% CI, 0.91 to 8.36; P = 0.041 [tested at alpha = 0.025]). The between-group difference was 18.66% (95% CI, 3.32% to 33.99%) in favour of bimekizumab 320 mg every 2 weeks.

BE HEARD II — The adjusted responder rate was 29.8% (95% CI, 18.9% to 40.7%) in the pooled bimekizumab 320 mg every 2 weeks group versus 10.2% (95% CI, 0.7% to 19.7%) in the placebo group (OR = 3.76; 97.5% CI, 1.189 to 11.867). The between-group difference was 19.57% (95% CI, 7.5% to 31.64%). Statistical significance could not be interpreted due to a prior nonsignificant result in the statistical testing hierarchy.

The HSSDD worst skin pain score response based on clinically meaningful change at week 48 was not assessed in either of the trials.

Harms Results

Harms data for the initial treatment period and overall treatment period are present for both trials.

Initial Treatment Period

In the initial study period, 67.1% of patients in the bimekizumab 320 mg every 2 weeks group and 66.6% in the placebo group reported at least 1 AE in the BE HEARD I trial compared to 64.5% of patients in the bimekizumab 320 mg every 2 weeks group and 56.8% in the placebo group in the BE HEARD II trial. The most frequently reported AEs (5% or more of study patients) in the BE HEARD I trial in the bimekizumab 320 mg every 2 weeks group versus the placebo group were hidradenitis (6.6% versus 13.9%, respectively), back pain (2.4% versus 8.3%, respectively), and headache (7.7% versus 4.2%, respectively), and in the BE HEARD II trial, diarrhea (6.2% versus 8.1%, respectively), headache (6.2% versus 9.5%, respectively), and hidradenitis (8.6% versus 6.8%, respectively).

The proportion of serious AEs reported in the pooled bimekizumab 320 mg every 2 weeks group was 2.8% in the BE HEARD I trial and 3.1% in the BE HEARD II trial. No serious AEs were reported in the placebo group in either study. In the BE HEARD I trial, 3.5% of patients in the pooled bimekizumab 320 mg every 2 weeks group and 1.4% of patients in the placebo group discontinued the study due to AEs. No patient in the placebo group and 4.1% of patients in the bimekizumab 320 mg every 2 weeks group discontinued the study due to AEs in the BE HEARD II trial. There were no deaths reported in either study.

Oral candidiasis was a notable harm identified by the experts consulted during the review. In the initial treatment period (safety set) of the BE HEARD I and II trials, oral candidiasis was reported in 5.9% and 8.3% of patients in the pooled bimekizumab 320 mg every 2 weeks groups, respectively. No oral candidiasis was reported in the placebo groups of either trial.

Overall Study Period

The approved Health Canada–recommended dose is bimekizumab 320 mg every 2 weeks for the first 16 weeks of treatment, followed by bimekizumab 320 mg every 4 weeks thereafter. Therefore, the most relevant treatment arm in the maintenance period (and overall period) is the bimekizumab 320 mg every 2 weeks then every 4 weeks group, and this group will be the focus of this harms summary.

In the overall treatment period (initial and maintenance treatment period), 85.5% of patients in the BE HEARD I trial versus 87.7% of patients in the BE HEARD II trial reported at least 1 AE in the bimekizumab 320 mg every 2 weeks then every 4 weeks group. The AEs (5% or more of study patients) most frequently reported by this group in the BE HEARD I trial included diarrhea (8.3%), oral candidiasis (11.0%), folliculitis (7.6%), and nasopharyngitis (8.3%). In the BE HEARD II trial, the most frequently reported AEs in this group included hidradenitis (21.2%), headache (9.6%), COVID-19 infection (10.3%), and oral candidiasis (17.1%). The proportion of serious AEs reported in the bimekizumab 320 mg every 2 weeks then every 4 weeks group was 5.5% in the BE HEARD I trial and 2.9% in the BE HEARD II trial. The incidence of AEs leading to study discontinuation for this group was 6.9% in 6.8% in the BE HEARD II trial. There were no deaths reported in either study.

All groups who received bimekizumab reported candida infections, most of which were oral candidiasis. In the BE HEARD I trial, 11.0% of the bimekizumab 320 mg every 2 weeks then every 4 weeks group reported oral candidiasis, while 17.1% of the bimekizumab 320 mg every 2 weeks then every 4 weeks group report oral candidiasis in the BE HEARD II trial. Additional AEs of special interest included fungal infections, hypersensitivity reactions, opportunistic infections, and injection-site reactions.

Critical Appraisal

Internal Validity

Two RCTs included in the systematic review were conducted using similar study and statistical methods. There were a few imbalances observed between the randomized treatment groups’ baseline characteristics, but these were not expected to affect efficacy findings. The proportion of patients who discontinued the study was similar across groups in the initial treatment period, and low overall as fewer than 10% of patients discontinued the study in any treatment group. Across all groups, the proportion of discontinuations in the maintenance treatment phase was higher than that of the initial treatment period. However, the rate of study discontinuations in both treatment periods of the BE HEARD I and II trials were not considered to have a substantial impact on the overall study findings. While there were many protocol deviations reported in both trials, most notably prohibited concomitant medication use, these deviations had minimal impact on the primary efficacy outcome.

The primary outcome (achievement of HiSCR50, tested at week 16) and key secondary outcomes in both trials and time points were generally consistent with the outcomes assessed in prior studies in HS populations. The statistical methods for the primary and secondary outcome analyses at week 16 in both trials were considered appropriate. After week 16, there was limited evidence of comparative efficacy of bimekizumab versus placebo for the key efficacy outcomes (achievement of HiSCR50, flares, HSSDD responder rates, and DLQI score). Due to the lack of control for multiplicity for other secondary ranked outcomes and outcomes investigated at week 48, the results for other secondary end points and outcomes at week 48 were considered exploratory. There were also concerns for substantial missing data for the patient-reported outcome questionnaires (DLQI and HSSDD) at week 16 and 48.

Although patients and investigators were blinded to study treatments, the observed imbalance in reported AEs for patients receiving bimekizumab, notably oral candidiasis, may have increased the likelihood that patients and investigators were aware of treatment assignments. There is also a potential risk of assessment bias for the evaluation of subjective outcomes such as HiSCR and flares, which are physician-assessed and prone to interobserver variation in the assessment of lesion counts. Similarly, it is possible that response bias could have influenced patient-reported outcomes, such as skin pain response and HRQoL (assessed using the DLQI), as these required subjective reporting by patients.

External Validity

The patient populations included in the trials were generally in line with patients seen in clinical practice in Canada with respect to age, sex, Hurley stage disease, duration of disease, and prior antibiotic use. The experts noted that, in their experience, the duration of HS and time to diagnosis was consistent with patients in current practice. There were no major generalizability concerns regarding the baseline and demographic characteristics of the patients enrolled in the trials. Both studies were multinational studies with multiple sites and many patients were enrolled from Canada.

While the choice of placebo as a comparator in both studies was sufficient for assessing the efficacy and safety of bimekizumab in patients with HS, adalimumab would have been an ideal active comparator to evaluate relative effectiveness. The concomitant medications and procedures that were allowed during the trials aligned with clinical practice. There were no concerns with the rescue medications administered during the trials as they align with drugs available in current practice.

The bimekizumab dosing and treatment schedule used in both trials aligns with the approved Health Canada–recommended dose, which is bimekizumab 320 mg every 2 weeks for the first 16 weeks of treatment, followed by bimekizumab 320 mg every 4 weeks thereafter. While both studies included a group that received bimekizumab 320 mg every 4 weeks for the initial treatment period (first 16 weeks), the efficacy and safety results from this group were not summarized for the purposes of this review, as the dosing schedule was outside of the approved indication. Although the 16-week duration of the initial treatment period was adequate to assess the clinical benefit of bimekizumab versus placebo in a clinical trial setting, the consulted clinical experts noted that a 6-month assessment is more applicable to clinical practice as HS is often slow to respond to treatment. The experts noted that if after 16 weeks of treatment a patient’s HS does not show any response to treatment and/or show disease worsening, they would consider discontinuing the treatment. During the maintenance treatment period, patients received bimekizumab either biweekly or monthly from week 16 to week 48. According to the consulted clinical experts, both dosage schedules (biweekly and monthly) are applicable to clinical practice, as patients will likely require different dosage frequencies depending on disease stability. However, it is worth noting that the approved Health Canada dosing recommendations for bimekizumab follow a fixed schedule and do not suggest adjusting dosage frequency based on treatment response.

The 48-week duration of treatment limits the generalizability of the findings from both trials as it does not provide sufficient long-term evidence of the safety and efficacy of bimekizumab treatment. Given that HS is a chronic, lifelong condition with no cure, there is a need for comprehensive long-term evaluation. Extended follow-up with an appropriate active comparator is necessary to understand the long-term efficacy and safety of bimekizumab in patients with moderate to severe HS.

GRADE Summary of Findings and Certainty of the Evidence

Methods for Assessing the Certainty of the Evidence

For the pivotal studies and RCTs identified in the sponsor’s systematic review, Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of the evidence for outcomes considered most relevant to inform CDA-AMC expert committee deliberations, and a final certainty rating was determined as outlined by the GRADE Working Group.

Following the GRADE approach, evidence from RCTs started as high-certainty evidence and could be rated down for concerns related to study limitations (which refers to internal validity or risk of bias), inconsistency across studies, indirectness, imprecision of effects, and publication bias.

When possible, certainty was rated in the context of the presence of an important (nontrivial) treatment effect; if this was not possible, certainty was rated in the context of the presence of any treatment effect (i.e., the clinical importance is unclear). In all cases, the target of the certainty of evidence assessment was based on the point estimate and where it was located relative to the threshold for a clinically important effect (when a threshold was available) or to the null.

The reference points for the certainty of evidence assessment for HiSCR50, flares, notable harms, and HSSDD worst skin pain was set according to the presence or absence of an important effect based on thresholds informed by the clinical experts consulted for this review. The reference point for the certainty of evidence assessment for DLQI total score was set according to the presence or absence of an important effect based on the threshold identified by the sponsor and clinical experts.

For the GRADE assessments, the findings from the BE HEARD I and BE HEARD II trials were considered together and summarized narratively per outcome because these trials were similar in population, interventions, design, and outcome measures.

The selection of outcomes for GRADE assessment was based on the sponsor’s Summary of Clinical Evidence, consultation with clinical experts, and input received from patient and clinician groups and public drug plans. The following list of outcomes was finalized in consultation with expert committee members:

• proportion of patients who achieved HiSCR50 by week 16

• proportion of patients who experienced a flare by week 48

• proportion of patients who reported at least a 3-point reduction in HSSDD worst skin pain score by week 16

• change from baseline in the DLQI total score by week 16

• proportion of patients with 1 or more serious AEs by week 16

• proportion of patients who experienced oral candidiasis by week 16.

Results of GRADE Assessments

Table 3 presents the GRADE summary of findings for bimekizumab 320 mg every 2 weeks versus placebo.

Table 3: Summary of Findings for Bimekizumab vs. Placebo for Patients With Hidradenitis Suppurativa

AN = abscesses and nodules; CI = confidence interval; DLQI = Dermatology Life Quality Index; HiSCR50 = Hidradenitis Suppurativa Clinical Response 50; HSSDD = Hidradenitis Suppurativa Symptom Daily Diary; HRQoL = health-related quality of life; LS = least squares; MID = minimal important difference; q.2.w. = every 2 weeks; q.4.w. = every 4 weeks; NR = not reported; RCT = randomized controlled trial; SAE = serious adverse event; vs. = versus.

Notes: Study limitations (which refers to internal validity or risk of bias), inconsistency across studies, indirectness, imprecision of effects, and publication bias were considered when assessing the certainty of the evidence. All serious concerns in these domains that led to the rating down of the level of certainty are documented in the table footnotes.

^aBased on clinical expert input, a threshold for a clinically important between-group difference was 100 per 1,000 for the proportion of patients with HiSCR50. Rated down 1 level for imprecision. The 95% CI interval for difference between groups includes the possibility of no difference.

^bAll patients received bimekizumab from week 16 to week 48; therefore, there is no longer a comparative analysis with a relevant comparator (or placebo) beyond 16 weeks (i.e., for the assessment at week 48). In the absence of a comparator group, conclusions about efficacy relative to any comparator cannot be drawn and the certainty of evidence started at very low and could not be rated up.

^cRated down 1 level for serious imprecision. The MID of 4 points for the DLQI score was selected as the threshold for a clinically important between-group difference based on the literature and clinical expert input. The 97.5% CI for between-group difference in the BE HEARD I trial included the potential for important benefit.

^dRated down 1 level for serious imprecision. An MID of 250 per 1,000 (i.e., 25%) was selected as a threshold for a clinically meaningful important between-group difference based on clinical expert input. Rated down 1 level for serious study limitations (i.e., risk of bias due to missing data).

^eIn the absence of a threshold for clinical importance, the null was used. Rated down 1 level for indirectness. The follow-up duration was limited to 16 weeks, which may be insufficient to detect uncommon SAEs or those that may develop over time.

Sources: BE HEARD I Clinical Study Report; BE HEARD II Clinical Study Report.

Long-Term Extension Studies

Patients who had completed the maintenance treatment period of the BE HEARD I and II trials were eligible to enroll in a separate open-label, noncontrolled extension trial, BE HEARD EXT (NCT04901195). The objective of the extension trial is to evaluate 2 bimekizumab dosing regimens (320 mg every 2 weeks and 320 mg every 4 weeks). This study remains ongoing at the time of submission and was not submitted for this review.

Indirect Comparisons

Description of Studies

The sponsor submitted indirect evidence in the form of an NMA and a MAIC.

For outcomes reported between weeks 12 to 16, NMAs were conducted by the sponsor. Two NMA networks were analyzed that compared bimekizumab to secukinumab and adalimumab. One network included a mixed population of patients with biologic experience plus patients without biologic experience (9 trials; N = 3,129; approximately 20% of patients had biologic experience). The sponsor also analyzed a network consisting of exclusively patients with biologic experience (4 trials; N = not reported).

An unanchored MAIC was used to assess the relative efficacy of bimekizumab with secukinumab and adalimumab after 48 to 52 weeks of treatment because it was not possible to form a connected network within the NMA for these time points.

Efficacy Results

Network Meta-Analysis

Mixed Biologic-Experienced and Biologic-Naive Population

For the binary outcomes, the results of the HiSCR50 analysis favoured bimekizumab every 2 weeks over secukinumab every 2 weeks (OR = 1.70; 95% CrI, 1.16 to 2.45) and over secukinumab every 4 weeks (OR = 1.69; 95% CrI, 1.14 to 2.43) for the fixed-effects models. The results observed in the random-effects model had 95% CrIs that crossed the null for the comparison of bimekizumab every 2 weeks versus secukinumab every 2 weeks (██ ██████ ███ ████ ████ ██ ████) and versus secukinumab every 4 weeks (██ █ █████ ███ ███ ████ ██ ████).

The results of the HiSCR50 analysis for the comparison of bimekizumab every 2 weeks versus adalimumab every week did not favour either treatment, with a 95% CrI that crossed the null for the fixed-effects model (OR = 1.30; 95% CrI, 0.85 to 1.92) and the random-effects model ███ █ █████ ███ ████ ████ ██ ████).

The results of the HiSCR75 analysis favoured bimekizumab every 2 weeks over secukinumab every 2 weeks (OR = 2.02; 95% CrI, 1.38 to 3.20) and over secukinumab every 4 weeks (OR = 1.85; 95% CrI, 1.26 to 2.90) for the fixed-effects models. The results of the HiSCR75 analysis favoured bimekizumab every 2 weeks over secukinumab every 2 weeks (██ █ █████ ███ ████ ████ ██ ████) and over secukinumab every 4 weeks (██ █ █████ ███ ████ ████ ██ ████) for the random-effects models.

The results of the HiSCR75 analysis favoured bimekizumab every 2 weeks over adalimumab every week (OR = 1.60; 95% CrI, 1.10 to 2.60) for the fixed-effects model. In the random-effects model, the results of the HiSCR75 analysis for the comparison of bimekizumab every 2 weeks versus adalimumab every week did not favour either treatment, with 95% CrIs that crossed the null (██ █ █████ ███ ████ ████ ██ ████).

The results for the random-effects models show greater imprecision and some of the results that favoured bimekizumab in the fixed-effects models do not show the same degree of benefit in the random-effects models (the CrI cross the null). The sponsor did not provide adequate justification for relying solely on the results of the fixed-effects models; therefore, the random-effects models need to be considered in the evaluation of the relative efficacy of bimekizumab.

For the continuous outcome of mean change from baseline in DLQI score, the 95% CrI crossed the null for the comparison of bimekizumab every 2 weeks versus adalimumab every week (███ █ █████ ███ ████ █████ ██ ████).

No analyses of AEs were reported.

Subgroup With Biologic Experience

There was no difference observed for bimekizumab versus secukinumab for achievement of HiSCR50 or any other outcome relevant for this review in this subgroup. There were no comparative data available for bimekizumab versus adalimumab for the subgroup with biologic experience.

Matching-Adjusted Indirect Comparison

Bimekizumab Versus Secukinumab (at Week 52)

The results of the MAIC favour bimekizumab every 2 weeks and every 4 weeks over secukinumab every 2 weeks and over secukinumab every 4 weeks for achievement of HiSCR50, HiSCR75, HiSCR90, and DLQI score minimal clinically important difference 5-point reduction. The 95% CIs do not cross the null for any of these comparisons.

Bimekizumab Versus Adalimumab (at Week 48)

The results of the MAIC favour bimekizumab every 2 weeks over adalimumab for HiSCR50 but not for HiSCR75 and HiSCR90. The 95% CIs do not cross the null for the HiSCR50 results, but the 95% CIs cross the null for the HiSCR75 and the HiSCR90 results.

Critical Appraisal

Network Meta-Analysis

The sponsor conducted an NMA using a Bayesian approach. This was a reasonable method to apply given the common comparator of placebo. The outcomes selected by the sponsor were relevant, though the sponsor did not present results for all outcomes originally included in their literature search. The time point of 12 to 16 weeks was a relevant point at which to assess efficacy given the limitation of the trial data, but later time points would have been preferable to generate estimates of long-term efficacy in an NMA.

The presentation of 2 networks was reasonable. One network contained a mixed population of patients with and without biologic experience (9 trials; N = 3,129). From the BE HEARD trials, across all 3 treatment arms, 191 of 1,014 patients (18.8%) had biologic experience. Across the treatment arms in the SUNRISE and SUNSHINE trials, 255 of 1,084 patients (23.5%) had biologic experience. The lack of a network with 100% patients who were biologic naive is a weakness of the analyses as there are no relative efficacy estimates for this population. The other network contained populations with biologic experience.

In the mixed population of patients with and without biologic experience, several results demonstrated differences favouring bimekizumab over secukinumab and adalimumab, but these findings were not consistent across all outcomes. There were no differences observed for bimekizumab versus comparators for dermatology-related quality of life. The reason for the incongruity in the dermatology-related quality of life results compared to the HiSCR results is not clear. The results in the biologic-experienced network had wide CrIs and only presented data from 2 outcomes; therefore, there was no clearly demonstrated advantage of bimekizumab over secukinumab in this subgroup.

There were fewer results in which bimekizumab was favoured over adalimumab compared to the results in which bimekizumab was favoured over secukinumab.

Matching-Adjusted Indirect Comparison

The sponsor performed an unanchored MAIC because of the lack of a connected treatment network for the 48 to 52 week time points. This was an adequate justification for performing a MAIC. The selection of comparators was reasonable, according to the clinical experts consulted for this review. The MAIC analyses suggested that there were differences in outcomes favouring bimekizumab over secukinumab, and these were seen across several outcomes. However, the results versus adalimumab across the outcomes were not as consistent for the comparisons with secukinumab.

The sponsor’s list of 16 matching variables was reasonable, but there may have been important differences between the studies included in the MAIC that were not accounted for. In addition, some of the matching variable data were not available for all studies and all outcomes; therefore, not all analyses applied all matching variables. Study design differences cannot be adjusted for in the MAIC weighting procedures.

The sponsor did attempt to use prior biologic exposure as a matching variable, but there were no analyses in the MAIC for a population that was exclusively biologic naive or a population that was exclusively biologic experienced.

In the MAIC analyses, the estimated sample size for the bimekizumab group was reduced to 70% to 77% for the comparison to secukinumab, and 46% to 47% for the comparison to adalimumab.

Studies Addressing Gaps in the Evidence From the Systematic Review

No studies addressing gaps were submitted by the sponsor.

Economic Evidence

Cost and Cost-Effectiveness

Table 4: Summary of Economic Evaluation

AE = adverse event; BSC = best supportive care; CDA-AMC = Canada’s Drug Agency; HiSCR = Hidradenitis Suppurativa Clinical Response; HRQoL = health-related quality of life; HS = hidradenitis suppurativa; ICER = incremental cost-effectiveness ratio; ITC = indirect treatment comparison; LY = life-year; QALY = quality-adjusted life-year; vs. = versus.

^aThe sponsor assumed that all patients would receive adalimumab biosimilars.

Budget Impact

CDA-AMC identified the following key limitations with the sponsor’s analysis: the number of eligible patients is likely underestimated, treatment costs are likely underestimated, the uptake of bimekizumab is uncertain, and confidential prices for bimekizumab and comparators were used. CDA-AMC revised the sponsor’s submitted analysis by aligning the estimates for the prevalence of HS and the proportion of patients eligible for public drug coverage with published literature from Canada. In the CDA-AMC base case, the budget impact of reimbursing bimekizumab for adult patients with moderate to severe HS with an inadequate response to conventional systemic therapy is expected to be $137,492,877 (year 1 = $4,457,321; year 2 = $44,640,920; year 3 = $88,394,636). The estimated budget impact is highly sensitive to the prevalence of HS.

Request for Reconsideration

The sponsor filed a request for reconsideration of the draft recommendation for bimekizumab for the treatment of adult patients with moderate to severe HS with an inadequate response to conventional systemic therapy. In their request, the sponsor identified the following issues:

• The sponsor cited inconsistency in the appraisal of the primary outcome, HiSCR50 for the bimekizumab review and the secukinumab review, and is requesting that CDA-AMC and CDEC apply the same standards used in the secukinumab review when evaluating HiSCR50 for the bimekizumab review.

• The sponsor requested that HiSCR75 be incorporated as a clinically meaningful and relevant efficacy end point and that it is assessed using the GRADE approach.

• The sponsor requested that HRQoL outcomes be evaluated using a consistent and comprehensive approach. The sponsor is of the view that including EQ-5D would better capture patient perceived improvements and ensure HRQoL is fully reflected in the clinical value assessment.

• The sponsor requested that CDA-AMC and CDEC interpret flares and antibiotic-handling approaches in the BE HEARD trials in the context of the disease. The sponsor noted that the statistical analysis section of both trials treated any rescue antibiotic use (even unrelated to HS) as a flare and a nonresponse on HiSCR and all other binary end points. According to the sponsor, this reflects a methodological artifact, not an accurate representation of bimekizumab’s efficiency.

• The sponsor requested that CDA-AMC and CDEC reconsider the indirect evidence and apply the same standards used in the secukinumab review when evaluating the ITC submitted for bimekizumab. According to the sponsor, the ITC findings demonstrate that bimekizumab performs at least comparably to adalimumab and secukinumab.

• The sponsor is requesting that CDEC fully consider patient and clinician group inputs in the bimekizumab recommendation as they are of the view that robust patient and clinician input were not incorporated consistently or equitably during the appraisal of bimekizumab.

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

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

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

• feedback on the draft recommendation from 2 patient groups (the CSPA and HS & Me)

• feedback on the draft recommendation from 6 clinician groups (the Dermatology Association of Ontario, Greater Vancouver Medical Dermatologists and Associates, the Atlantic Dermatology Group, the Saskatchewan Dermatology Association, the Canadian Dermatology Association’s Pharmacy and Therapeutics Advisory Board, and the Canadian Hidradenitis Suppurativa Foundation)

• feedback on the draft recommendation from the public drug plans that participate in the reimbursement review process.

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

Additional Evidence Considered as Part of the Reconsideration

Additional evidence that was included in the original submission was considered in further detail as part of the reconsideration.

Assessment of HiSCR50 Based on Pooled Data

Efficacy data from the BE HEARD I and BE HEARD II trials were combined in a pool E1 efficacy analysis to yield estimates of the treatment effect of bimekizumab versus placebo with greater precision based on this combined population. The identically designed phase III studies had the same eligibility criteria, doses, dosage forms, and dosing schedules from baseline to week 16. The CDA-AMC review team noted that the use of pooled data and the statistical methods for pooling the studies was considered appropriate, was preplanned, and was also accepted by Health Canada.

HiSCR50 rates at week 16 for pooled data:

• Bimekizumab: 477 per 1,000 (95% CI, 414 to 540 per 1,000)

• Placebo: 288 per 1,000 (95% CI, 204 to 373 per 1,000)

• Risk difference: 189 per 1,000 (104 to 270 per 1,000)

Using the threshold of 10% (100 per 1,000 patients), the evidence for the pooled data for both trials would have been rated as high certainty. There were no concerns with imprecision given that the upper and lower bounds of the 95% CI exceeded the threshold suggested by the clinical experts consulted by CDA-AMC (10%). There were no concerns with the statistical analysis techniques implemented to pool the data as the analyses aligned with the techniques highlighted in the statistical analysis plan.

It was concluded that bimekizumab results in a clinically important increase in the proportion of patients achieving a greater than or equal to 50% reduction from baseline in total AN count, with no increase from baseline in abscess or draining tunnel count (HiSCR50) when compared to placebo.

Supplemental GRADE Assessment for HiSCR75

The review team performed a GRADE assessment of the HiSCR75 results for the committee’s awareness. In the absence of a published MID, the same 10% threshold suggested by the clinical experts consulted by CDA-AMC for HiSCR50 was applied to the HiSCR75 outcome.

BE HEARD I:

• Bimekizumab: 357 per 1,000 (270 to 444 per 1,000)

• Placebo: 203 per 1,000 (94 to 312 per 1,000)

• Difference: 154 per 1,000 (37 to 270 per 1,000)

BE HEARD II:

• Bimekizumab: 368 per 1,000 (284 to 452 per 1,000)

• Placebo: 163 per 1,000 (68 to 257 per 1,000)

• Difference: 206 per 1,000 (99 to 313 per 1,000)

The evidence was rated as moderate certainty because it was rated down 1 level for imprecision. The 95% CI interval for the difference between groups includes the possibility of no difference (i.e., the lower bound is less than 100 per 1,000 [10%]); therefore bimekizumab 320 mg every 2 weeks likely results in an increase in the proportion of patients with HiSCR75 when compared with placebo.

EQ-5D-3L VAS Results

While both trials included several patient-reported HRQoL evaluations (DLQI, HiSQOL, EQ-5D-3L VAS), only change from baseline in DLQI total score was assessed as a key ranked secondary end point at week 16 in the BE HEARD I and II trials. According to the sponsor’s input, the mean change from baseline (standard error [SE]) in EQ-5D-3L VAS scores at week 16 were higher in the bimekizumab 320 mg every 2 weeks group than in the placebo groups in both studies:

• BE HEARD I: bimekizumab 320 mg every 2 weeks mean change from baseline = 7.1 (SE = 1.1); placebo mean change from baseline = 0.7 (SE = 2.7)

• BE HEARD II: bimekizumab 320 mg every 2 weeks mean change from baseline = 5.3 (SE = 1.0); placebo mean change from baseline = 0.9 (SE = 2.2)

The results of the change from baseline in EQ-5D-3L VAS score were greater in the bimekizumab groups than in the placebo groups, but there is no evidence of an MID included in the submission to inform the clinical relevance of this change. Further, the between-group difference was not reported.

CDEC Information

Initial Meeting Date: March 27, 2025

Members of the committee: Dr. Peter Jamieson (Chair), Dr. Sally Bean, Daryl Bell, Dan Dunsky, Dr. Trudy Huyghebaert, Morris Joseph, Dr. Dennis Ko, Dr. Christine Leong, Dr. Kerry Mansell, Alicia McCallum, Dr. Srinivas Murthy, Dr. Nicholas Myers, Dr. Krishnan Ramanathan, Dr. Marco Solmi, Dr. Edward Xie, and Dr. Peter Zed.

Regrets: Three expert committee members did not attend.

Conflicts of interest: None

Reconsideration Meeting Date: March 25, 2026

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.

Regrets: Five expert committee members did not attend.

Conflicts of interest: None