Bimekizumab

1 INDICATIONS AND USAGE BIMZELX is a humanized interleukin-17A and F antagonist indicated for the treatment of: Moderate to severe plaque psoriasis (PSO) in adults who are candidates for systemic therapy or phototherapy. ( 1.1 ) Adults with active psoriatic arthritis (PsA) . ( 1.2 ) Adults with active non-radiographic axial spondyloarthritis ( nr-axSpA ) with objective signs of inflammation. ( 1.3 ) Adults with active ankylosing spondylitis ( AS ). ( 1.4 ) Adults with moderate to severe hidradenitis suppurativa (HS) . ( 1.5 ) 1.1 Plaque Psoriasis BIMZELX is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. 1.2 Psoriatic Arthritis BIMZELX is indicated for the treatment of adults with active psoriatic arthritis. 1.3 Non-Radiographic Axial Spondyloarthritis BIMZELX is indicated for the treatment of adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation. 1.4 Ankylosing Spondylitis BIMZELX is indicated for the treatment of adults with active ankylosing spondylitis. 1.5 Hidradenitis Suppurativa BIMZELX is indicated for the treatment of adults with moderate to severe hidradenitis suppurativa.

2 DOSAGE AND ADMINISTRATION Prior to treatment: ( 2.1 ) Evaluate patients for tuberculosis infection. Test liver enzymes, alkaline phosphatase, and bilirubin. Complete all age-appropriate vaccinations as recommended by current immunization guidelines. Plaque Psoriasis Administer 320 mg by subcutaneous injection at Weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing 120 kg or more, consider a dose of 320 mg every 4 weeks after Week 16. ( 2.2 ) Psoriatic Arthritis Administer 160 mg by subcutaneous injection every 4 weeks. ( 2.3 ) For patients with coexisting moderate to severe plaque psoriasis, use the dosage and administration for plaque psoriasis. ( 2.2 ) Non-Radiographic Axial Spondyloarthritis Administer 160 mg by subcutaneous injection every 4 weeks. ( 2.4 ) Ankylosing Spondylitis Administer 160 mg by subcutaneous injection every 4 weeks. ( 2.5 ) Hidradenitis Suppurativa Administer 320 mg by subcutaneous injection at Week 0, 2, 4, 6, 8, 10, 12, 14 and 16, then every 4 weeks thereafter. ( 2.6 ) See full prescribing information for recommendations regarding missed doses, preparation and administration instructions. ( 2.7 , 2.8 , 2.9 ) 2.1 Recommended Evaluations and Immunization Prior to Treatment Initiation Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with BIMZELX [see Warnings and Precautions (5.3) ] . Test liver enzymes, alkaline phosphatase and bilirubin prior to initiating treatment with BIMZELX [see Warnings and Precautions (5.4) ] . Complete all age-appropriate vaccinations as recommended by current immunization guidelines [see Warning and Precautions (5.6) ] . 2.2 Recommended Dosage for Plaque Psoriasis The recommended dosage is 320 mg by subcutaneous injection at Weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter . For patients weighing 120 kg or more, consider a dosage of 320 mg every 4 weeks after Week 16 [see Clinical Pharmacology (12.3) ] . 2.3 Recommended Dosage for Psoriatic Arthritis The recommended dosage is 160 mg by subcutaneous injection every 4 weeks. For psoriatic arthritis patients with coexistent moderate to severe plaque psoriasis, use the dosing regimen for adult patients with plaque psoriasis [see Dosage and Administration (2.2) ] . 2.4 Recommended Dosage for Non-Radiographic Axial Spondyloarthritis The recommended dosage is 160 mg by subcutaneous injection every 4 weeks. 2.5 Recommended Dosage for Ankylosing Spondylitis The recommended dosage is 160 mg by subcutaneous injection every 4 weeks. 2.6 Recommended Dosage for Hidradenitis Suppurativa The recommended dosage is 320 mg by subcutaneous injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, and 16, then every 4 weeks thereafter. 2.7 Missed Doses If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regularly scheduled interval. 2.8 Preparation Instructions Before injecting, remove the carton with BIMZELX from the refrigerator and allow BIMZELX to reach room temperature (30 to 45 minutes) without removing the prefilled syringes or autoinjectors from the carton to protect from light. Inspect visually for particulate matter and discoloration prior to administration, whenever solution and container permit. BIMZELX injection is clear to slightly opalescent, and colorless to pale brownish- yellow. Do not use if the solution contains visible particles, is discolored or cloudy. 2.9 Administration Instructions BIMZELX is intended for use under the guidance and supervision of a healthcare professional. Patients may self-inject after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of BIMZELX according to the "Instructions for Use" [see Instructions for Use]. If two separate 160 mg injections are used to achieve the recommended dose, administer each injection subcutaneously at a different anatomic location (such as thighs, abdomen or back of upper arm). Discard the syringes or autoinjectors after use. Do not reuse. Do not inject BIMZELX within 2 inches (5 cm) of the navel or into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis. Administration of BIMZELX in the upper, outer arm may only be performed by a healthcare professional or caregiver. Rotate the injection site with each injection.

6 ADVERSE REACTIONS The following adverse reactions have been observed with BIMZELX and are discussed in greater detail in other sections of the labeling: Suicidal Ideation and Behavior [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Liver Biochemical Abnormalities [see Warnings and Precautions (5.4) ] Inflammatory Bowel Disease [see Warnings and Precautions (5.5) ] Most common adverse reactions are: Psoriasis and Hidradenitis Suppurativa (incidence ≥ 1%): upper respiratory tract infections, oral candidiasis, headache, injection site reactions, tinea infections, gastroenteritis, Herpes simplex infections, acne, folliculitis, other candida infections, and fatigue. ( 6.1 ) Psoriatic Arthritis (incidence ≥ 2%): upper respiratory tract infections, oral candidiasis, headache, diarrhea, and urinary tract infection. ( 6.1 ) Non-Radiographic Axial Spondyloarthritis (incidence ≥ 2%): upper respiratory tract infections, oral candidiasis, headache, diarrhea, cough, fatigue, musculoskeletal pain, myalgia, tonsilitis, transaminase increase, and urinary tract infection. ( 6.1 ) Ankylosing Spondylitis (incidence ≥ 2%): upper respiratory tract infections, oral candidiasis, headache, diarrhea, injection site pain, rash and vulvovaginal mycotic infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc. at 844-599-2273 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Plaque Psoriasis Clinical Trials In clinical trials, a total of 1,789 subjects with plaque psoriasis were treated with BIMZELX. Of these, 1,073 subjects were exposed to BIMZELX for at least one year. The safety of BIMZELX was evaluated in two placebo-controlled trials (Ps-1 and Ps-2), an active-controlled trial (Ps-3), and an open-label extension trial. Data from Trials Ps-1 and Ps-2 in 839 subjects (mean age 45 years, 72% male, 84% White) were pooled to evaluate the safety of BIMZELX in comparison to placebo up to 16 weeks after treatment initiation. A total of 670 subjects were treated during this initial period with BIMZELX 320 mg at Weeks 0, 4, 8, 12, and 16. Table 1 summarizes the adverse reactions that occurred at a rate of 1% or greater and at a higher rate in the BIMZELX group than the placebo group. Table 1: Adverse Reactions Occurring in ≥1% of Subjects with Plaque Psoriasis in the BIMZELX Group and More Frequently than in the Placebo Group in Trials Ps-1 and Ps-2 BIMZELX N=670 n (%) Placebo N=169 n (%) URI Upper Respiratory Infections include nasopharyngitis, upper respiratory tract infection, pharyngitis, rhinitis, viral upper respiratory tract infection, tonsillitis, sinusitis, pharyngitis streptococcal, pharyngitis bacterial, peritonsillar abscess, viral rhinitis, and influenza 102 (15) 24 (14) Oral Candidiasis Oral Candidiasis includes oral candidiasis, oropharyngeal candidiasis, oral fungal infection, fungal pharyngitis, and oropharyngitis fungal 61 (9) 0 (0) Headache 22 (3) 0 (0) Injection Site Reactions Injection Site Reactions include injection site reaction, injection site erythema, injection site pain, injection site edema, injection site bruising, and injection site swelling 19 (3) 2 (1) Tinea Infections Tinea Infections include tinea pedis, fungal skin infection, tinea versicolor, tinea cruris, tinea infection, body tinea, and onychomycosis 18 (3) 1 (1) Gastroenteritis Gastroenteritis includes Enterovirus infection, gastroenteritis, gastroenteritis bacterial, and gastroenteritis viral 12 (2) 0 (0) Herpes Simplex Infections Herpes Simplex Infections include herpes simplex and oral herpes 9 (1) 0 (0) Acne 8 (1) 0 (0) Folliculitis 8 (1) 0 (0) Other Candida Infections Other Candida Infections include vulvovaginal candidiasis, vulvovaginal mycotic infection, skin candida, and genital candidiasis. 7 (1) 1 (1) Fatigue 7 (1) 0 (0) Adverse reactions that occurred in < 1% but > 0.1% of subjects in the BIMZELX group and at a higher rate than in the placebo group through Week 16 were neutropenia, eczema, otitis externa, otitis media, and pyrexia. The safety of BIMZELX was evaluated in another active-controlled trial (Ps-4) in 743 adult subjects who received BIMZELX 320 mg every 4 weeks or every 8 weeks through Week 48. Specific Adverse Reactions Suicidal Ideation and Behavior : The study populations of Trial Ps-1, Trial Ps-2, Trial Ps-3 and Trial Ps-4 excluded subjects with active suicidal ideation, suicidal ideation within the month prior to screening, a history of suicide attempt within the past 5 years prior to screening, or moderately severe to severe major depression (i.e., score of ≥15 on the screening Patient Health Questionnaire-9 (PHQ-9)). Analysis of pooled C-SSRS data from the first 16 weeks of placebo-controlled clinical trials indicated that 12/670 (1.8%) BIMZELX-treated subjects and 1/169 (0.6%) subjects receiving placebo reported passive suicidal ideation with an estimated relative risk of 3.0 (95% confidence interval: 0.39, 22.74). Subjects without a prior history of SI/B treated with BIMZELX also reported a higher rate of new onset suicidal ideation on the C-SSRS than subjects receiving placebo (1.3% vs 0.6%). During the course of the clinical trials for plaque psoriasis, there was 1 completed suicide in the open label extension trial after 718 days of treatment (1/2,480; 0.01/100 patient-years). The completed suicide was reported in a subject without a past reported psychiatric history. There were also 3 suicide attempts (3/2,480; 0.04/100 patient-years); 2 of these subjects had a history of prior suicide attempts. Infections : During the placebo-controlled period of Trials Ps-1 and Ps-2, infections were reported in 36% of subjects (141.7 per 100 patient-years) treated with BIMZELX compared with 23% of subjects (84.6 per 100 patient-years) receiving placebo. Serious infections occurred in 0.3% of subjects (1.0 per 100 patient-years) treated with BIMZELX and 0% subjects receiving placebo . The most common infections were upper respiratory tract infections and Candida infections, including oral candidiasis (oral candidiasis, oropharyngeal candidiasis, oral fungal infection, fungal pharyngitis, and oropharyngitis fungal) occurring in 9% (30.6 per 100 patient-years) of subjects treated with BIMZELX and other Candida infections (vulvovaginal candidiasis, vulvovaginal mycotic infection, skin candida, and genital candidiasis) in 1% (3.4 per 100 patient-years) of subjects treated with BIMZELX compared to 0% and 1%, respectively, of subjects receiving placebo. During the combined initial, maintenance, and open-label extension treatment periods of trials Ps-1, Ps-2, Ps-3, and the open-label extension trial, infections were reported in 63% of subjects treated with BIMZELX (120.4 per 100 patient-years). Serious infections were reported in 1.5% of subjects treated with BIMZELX (1.6 per 100 patient-years). Inflammatory Bowel Disease : In clinical trials in subjects with plaque psoriasis, subjects with active inflammatory bowel disease were excluded. In these trials, which included 2,480 subjects exposed to BIMZELX accounting for 5,830 patient-years, adjudicated cases of new onset of inflammatory bowel disease (including ulcerative colitis (UC), Crohn's disease (CD) and IBD-undetermined) occurred in seven subjects (0.12 per 100 patient-years); the majority of these cases were serious and resulted in discontinuation of therapy. Liver Biochemical Abnormalities : During the placebo-controlled period of Trials Ps-1 and Ps-2, liver serum transaminase elevations (> 3 times the upper limit of normal [ULN]) occurred in 1.0% of subjects treated with BIMZELX versus 0.6% of subjects receiving placebo. The time to onset of these adverse reactions varied between 28 and 198 days after starting BIMZELX treatment. Elevated liver serum transaminases resolved during continued treatment or after discontinuation of BIMZELX. Safety through Week 56 During the maintenance period (Week 16 through Week 52 of Trial Ps-1 and Week 56 of Trial Ps-2), adverse reactions were consistent with those observed during the initial 16 weeks of treatment with BIMZELX. During the maintenance treatment periods of Trial Ps-2 and Trial Ps-3, the rates of adverse reactions were similar between subjects treated with BIMZELX 320 mg every four week and every eight weeks, after the initial 16 weeks of treatment. Safety through Week 128 During the open-label extension trial, including data from Week 56 through Week 128, new adverse reactions of suicide attempt and a completed suicide occurred [described above in Suicidal Ideation and Behavior ]. Additional Safety Data In an active-controlled clinical trial (Trial Ps-4), 691 subjects with plaque psoriasis were treated with BIMZELX for up to 144 weeks. Adverse reactions were consistent with those observed during the initial 16 weeks of treatment and with the overall safety profile of BIMZELX. Psoriatic Arthritis Clinical Trials The safety of BIMZELX was evaluated in two placebo-controlled trials (PsA-1 and PsA-2). Data from Trials PsA-1 and PsA-2 in 1,111 subjects (mean age 49 years, 47% male, 96% White) were pooled to evaluate the safety of BIMZELX in comparison to placebo up to 16 weeks after treatment initiation. A total of 698 subjects were treated during this initial period with BIMZELX 160 mg at Weeks 0, 4, 8, 12, and 16. Table 2 summarizes the adverse reactions that occurred at a rate of 2% or greater and at a higher rate in the BIMZELX group than the placebo group. Table 2: Adverse Reactions Occurring in ≥2% of Subjects with Psoriatic Arthritis in the BIMZELX Group and More Frequently than in the Placebo Group in Trials PsA-1 and PsA-2 BIMZELX N=698 n (%) Placebo N=413 n (%) URI Upper Respiratory Tract Infections (URI) includes: nasopharyngitis, upper respiratory tract infection, pharyngitis, sinusitis, and rhinitis. 99 (14) 41 (10) Headache 25 (4) 7 (2) Diarrhea 19 (3) 8 (2) Urinary Tract Infection 14 (2) 7 (2) Oral Candidiasis 16 (2) 0 Adverse reactions that occurred in < 2% but > 1% of subjects in the BIMZELX group and at a higher rate than in the placebo group through Week 16 included neutropenia (placebo: n=0; BIMZELX: n=8 (1.1%)), stomatitis (placebo: n=0; BIMZELX: n=8 (1.1%)), bronchitis (placebo: n=1 (0.2%); BIMZELX: n=11 (1.6%)), and oropharyngeal pain (placebo: n=0; BIMZELX: n=9 (1.3%)). Specific Adverse Reactions Suicidal Ideation and Behavior: The neuropsychiatric inclusion/exclusion criteria in PsA trials were the same as in PSO. Based on a pooled analysis of the first 16 weeks of the placebo controlled clinical trials, 2 of the 698 subjects in the BIMZELX group (0.3%) reported passive suicidal ideation on the C-SSRS compared to 3 of 413 subjects in the placebo group (0.7%). During the entire clinical trial program for PsA (2,664 patient-years), there were 2 cases of suicidal ideation (2/1413; 0.08/100 patient-years) and 1 suicide attempt (1/1413; 0.04/100 patient-years); all reported in BIMZELX-treated subjects with pre-existing psychiatric conditions. Infections: During the placebo-controlled period of Trials PsA-1 and PsA-2, infections were reported in 27% of subjects (100.7 per 100 patient-years) treated with BIMZELX compared with 18% of subjects (62.8 per 100 patient-years) treated with placebo. Serious infections occurred in 0.4% of subjects (1.4 per 100 patient-years) treated with BIMZELX and 0% treated with placebo . The most common infections were upper respiratory tract infections, nasopharyngitis, urinary tract infection and Candida infections, including oral candidiasis (oral candidiasis, oral fungal infection, and tongue fungal infection), occurring in 3.2% (10.2 per 100 patient-years) of subjects treated with BIMZELX and other Candida infections (skin candida, vulvovaginal candidiasis, and vulvovaginal mycotic infection) in 0.6% (1.8 per 100 patient-years) of subjects treated with BIMZELX compared to 0% and 1%, respectively, of subjects treated with placebo. During the combined placebo-controlled, maintenance and open-label extension treatment periods of Trials PsA-1 and PsA-2, infections were reported in 58% of subjects treated with BIMZELX (58.5 per 100 patients-years). Serious infections were reported in 2% of subjects treated with BIMZELX (1.3 per 100 patient-years). Inflammatory Bowel Disease: In clinical trials in subjects with psoriatic arthritis, subjects with active inflammatory bowel disease were excluded. In these trials, which included 1,413 subjects exposed to BIMZELX accounting for 2,664 patient-years, adjudicated cases of new onset of inflammatory bowel disease (including ulcerative colitis (UC) and IBD) occurred in 2 subjects (0.08 per 100 patient-years); one of these cases was serious and none resulted in discontinuation of therapy. Liver Biochemical Abnormalities: During the placebo-controlled period of Trials PsA-1 and PsA-2, liver serum transaminase elevations (> 3 times the upper limit of normal [ULN]) occurred in 1.3% of subjects treated with BIMZELX versus 0% of subjects receiving placebo. Elevated liver serum transaminases resolved during continued treatment or after discontinuation of BIMZELX. Safety through Week 52 During the maintenance period (Week 16 through Week 52 of Trial PsA-1), adverse reactions were consistent with those observed during the initial 16 weeks of treatment and with the overall safety profile of BIMZELX. Non-Radiographic Axial Spondyloarthritis Clinical Trials BIMZELX was evaluated in a placebo-controlled trial (Trial nr-axSpA-1) in subjects with non-radiographic axial spondyloarthritis (128 subjects on BIMZELX and 126 subjects on placebo). The safety profile observed in subjects with non-radiographic axial spondyloarthritis treated with BIMZELX was overall similar to the safety profile seen in subjects with psoriatic arthritis, except for cough, musculoskeletal pain, myalgia, tonsilitis, transaminase increase (placebo: n=0; BIMZELX: n=3 (2.3%) for each), and fatigue (placebo: n=1 (0.8%); BIMZELX: n=3 (2.3%)). Specific Adverse Reactions Suicidal Ideation and Behavior: The neuropsychiatric inclusion/exclusion criteria were the same in non-radiographic axial spondyloarthritis trials as in PSO. During the first 16 weeks of the placebo controlled clinical trial (Trial nr-axSpA-1), no subjects in the BIMZELX or placebo group reported suicidal ideation on the C-SSRS. During the entire clinical trial program for nr-axSpA (398 patient-years), there were no cases of suicidal ideations. One suicide attempt (1/244; 0.25/100 patient-years) was reported in a BIMZELX-treated patient with pre-existing psychiatric conditions and recent life stressors. Infections: During the placebo-controlled period of Trial nr-axSpA-1, infections were reported in 36% of subjects (144.8 per 100 patient-years) treated with BIMZELX compared with 25% of subjects (94.4 per 100 patient-years) receiving placebo. There were no reports of serious infections reported during the placebo-controlled period of the trial. During the combined 52 week treatment period of Trial nr-axSpA-1, and subsequent open-label treatment, infections were reported in 68% of subjects treated with BIMZELX (78.0 per 100 patient-years). Serious infections were reported in 1.6% of subjects treated with BIMZELX (1.0 per 100 patient-years). Inflammatory Bowel Disease: In the clinical trial in subjects with non-radiographic axial spondyloarthritis, subjects with active inflammatory bowel disease were excluded. In placebo-controlled, maintenance, and open label treatment periods of this trial, which included 244 subjects exposed to BIMZELX accounting for 397 patient-years, adjudicated cases of new onset of inflammatory bowel disease occurred in 1 subject (Ulcerative Colitis; 0.26 per 100 patient-years); this case of ulcerative colitis was nonserious and did not result in discontinuation of therapy. Liver Biochemical Abnormalities: During the placebo-controlled period of Trials nr-axSpA-1, liver serum transaminase elevations (> 3 times the upper limit of normal [ULN]) occurred in 1.6% of subjects treated with BIMZELX versus 0.8% of subjects receiving placebo. Elevated liver serum transaminases resolved during continued treatment or after discontinuation of BIMZELX. Safety through Week 52 During the maintenance period (Week 16 through Week 52 of Trial nr-axSpA-1), adverse reactions were consistent with those observed during the initial 16 weeks of treatment and with the overall safety profile of BIMZELX. Ankylosing Spondylitis Clinical Trials BIMZELX was evaluated in a placebo-controlled trial (Trial AS-1) in subjects with ankylosing spondylitis (221 subjects on BIMZELX and 111 subjects on placebo). The safety profile observed in subjects with ankylosing spondylitis treated with BIMZELX was overall similar to the safety profile seen in subjects with psoriatic arthritis, except for injection site pain, rash (placebo: n=1 (0.9%); BIMZELX: n=6 (2.7%), for each) and vulvovaginal mycotic infection (placebo: n=0; BIMZELX: n=5 (2.3%)). Specific Adverse Reactions Suicidal Ideation and Behavior: The neuropsychiatric inclusion/exclusion criteria were the same in AS trials as in PSO. During the first 16 weeks of the placebo controlled clinical Trial AS-1, no subjects in the BIMZELX or placebo group reported suicidal ideation on the C-SSRS. During the entire clinical trial program for AS (1,844 patient-years), there was 1 case of suicidal ideation (1/684; 0.05/100 patient-years) reported in a subject with pre-existing psychiatric conditions. Infections: During the placebo-controlled period of Trial AS-1, infections were reported in 28% of subjects (110.3 per 100 patient-years) treated with BIMZELX compared with 23% of subjects (83.7 per 100 patient-years) receiving placebo. Serious infections occurred in 1 (0.5%) subject (1.5 per 100 patient-years) treated with BIMZELX and 1 (0.9%) subject (2.9 per 100 patient-years) receiving placebo . During the combined 52 week treatment period of Trial AS-1, and subsequent open-label treatment, infections were reported in 62% of subjects treated with BIMZELX (58.8 per 100 patient-years). Serious infections were reported in 2.7% of subjects treated with BIMZELX (1.5 per 100 patient-years). Inflammatory Bowel Disease: In clinical trials in subjects with AS, subjects with active inflammatory bowel disease were excluded. In these phase 2/3 trials, which included 593 subjects exposed to BIMZELX accounting for 1,599 patient-years, adjudicated cases of new onset of inflammatory bowel disease (including ulcerative colitis (UC), Crohn's disease (CD) and IBD-undetermined) occurred in 6 subjects (0.38 per 100 patient-years); 4 cases were serious, and 3 cases resulted in discontinuation of therapy. Liver Biochemical Abnormalities: During the placebo-controlled period of Trial AS-1, liver serum transaminase elevations (> 3 times the upper limit of normal [ULN]) occurred in 1.4% of subjects treated with BIMZELX versus 1.8% of subjects receiving placebo. Elevated liver serum transaminases resolved during continued treatment or after discontinuation of BIMZELX. Safety through Week 52 During the maintenance period (Week 16 through Week 52 of Trial AS-1), adverse reactions were consistent with those observed during the initial 16 weeks of treatment and with the overall safety profile of BIMZELX. Hidradenitis Suppurativa Clinical Trials BIMZELX was evaluated in two placebo-controlled trials (Trial HS-1 and Trial HS-2) in 1,007 adult subjects with moderate to severe hidradenitis suppurativa (861 BIMZELX-treated subjects and 146 subjects receiving placebo) [see Clinical Studies (14.5) ] . The safety profile observed in subjects with hidradenitis suppurativa treated with BIMZELX was overall similar to the safety profile seen in subjects with PSO treated with BIMZELX. Upon completion of both trials, a total of 657 subjects enrolled in a long-term extension treatment period for up to an additional 188 weeks. Specific Adverse Reactions Suicidal Ideation and Behavior : The neuropsychiatric inclusion/exclusion criteria were the same in HS trials as in PSO. Analysis of pooled C-SSRS data from the first 16 weeks of the placebo-controlled clinical trials indicated that 16/861 (1.9%) BIMZELX-treated subjects and 1/146 (0.7%) subjects receiving placebo reported suicidal ideation with an estimated relative risk of 2.70 (95% confidence interval: 0.36, 20.12). Subjects without a prior history of SI/B treated with BIMZELX also reported a higher rate of new-onset suicidal ideation on the C-SSRS than subjects treated with placebo (0.9% vs. 0%). There were 2 reported cases of suicidal ideation that were adjudicated as suicide attempts (2/1,041; 0.15/100 patient-years). Both subjects had a history of neuropsychiatric disorders. Infections: During the placebo-controlled period of Trials HS-1 and HS-2, infections were reported in 33% of subjects (132.2 per 100 patient-years) treated with BIMZELX compared with 21% of subjects (76.4 per 100 patient-years) receiving placebo. Serious infections occurred in 0.1% of subjects (0.4 per 100 patient-years) treated with BIMZELX and 0% of subjects receiving placebo . The most commonly reported infections were comparable to those reported in subjects with PSO. Oral candidiasis occurred in 7.8% of subjects (26.7 per 100 patient years) treated with BIMZELX 320 mg Q2W, 3.9% of subjects (12.9 per 100 patient-years) treated with BIMZELX 320 mg Q4W, and 0 subjects receiving placebo. Other candida infections occurred in 3.6% of subjects (12.2 per 100 patient-years) treated with BIMZELX 320 mg Q2W, 6.7% of subjects (22.6 per 100 patient-years) treated with BIMZELX 320 mg Q4W, and 0 subjects receiving placebo. Tinea infections occurred in 3.1% of subjects (10.4 per 100 patient-years) treated with BIMZELX 320 mg Q2W, 2.5% of subjects (8.1 per 100 patient-years) treated with BIMZELX 320 mg Q4W, and 0.7% (2.3 per 100 patient-years) receiving placebo. During the combined placebo-controlled, maintenance treatment periods and open-label extension treatment periods of Trials HS-1 and HS-2, infections were reported in 68% of subjects treated with BIMZELX (104.7 per 100 patient-years). Serious infections were reported in 2.1% of subjects treated with BIMZELX (1.7 per 100 patient-years). Inflammatory Bowel Disease: In clinical trials in subjects with hidradenitis suppurativa, subjects with active inflammatory bowel disease were excluded. During the combined placebo-controlled, maintenance, and open-label extension treatment periods of Trials HS-1 and HS-2, which included 995 subjects exposed to BIMZELX accounting for 1,272 patient-years, adjudicated cases of new onset of inflammatory bowel disease (including ulcerative colitis (UC), Crohn's disease (CD) and undetermined) occurred in 5 subjects (0.39 per 100 patient-years); 3 of these cases were serious, all of which resulted in discontinuation of therapy. Additionally, flares of pre-existing IBD occurred in 2 subjects, which resulted in discontinuation of BIMZELX in both. Liver Biochemical Abnormalities: During the placebo-controlled period of Trials HS-1 and HS-2, liver serum transaminase elevations (> 3 times the upper limit of normal [ULN]) occurred in 1.2% of subjects treated with BIMZELX versus 0% of subjects receiving placebo. Elevated liver serum transaminases resolved during continued treatment or after discontinuation of BIMZELX. Safety through Week 48 During the maintenance period (Week 16 through Week 48 of Trials HS-1 and HS-2), adverse reactions were consistent with those observed during the initial 16 weeks of treatment and with the overall safety profile of BIMZELX. 6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval use of BIMZELX. Because they are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Infections: conjunctivitis, esophageal candidiasis

12.3 Pharmacokinetics Bimekizumab-bkzx pharmacokinetics are comparable in adult patients with moderate to severe plaque psoriasis, psoriatic arthritis, non-radiographic axial spondyloarthritis, and ankylosing spondylitis. The median peak plasma concentration of bimekizumab-bkzx was 25 (range: 12-50) μg/mL and was reached in 3-4 days. Bimekizumab-bkzx exhibited dose-proportional pharmacokinetics in patients with plaque psoriasis over a dose range of 64 mg to 480 mg (0.2 to 1.5 times the approved recommended dosage) following subcutaneous administration. The median steady-state trough concentration of bimekizumab-bkzx was approximately 40% lower in HS subjects than that of PSO subjects. Absorption The absolute bioavailability of bimekizumab-bkzx was 70% in healthy subjects. Distribution The median volume of distribution at steady state was 11.2 L in subjects with moderate to severe plaque psoriasis. The volume of distribution in subjects with moderate to severe hidradenitis suppurativa was estimated to be approximately 18% higher than in subjects with moderate to severe plaque psoriasis. Elimination The median (coefficient of variation %) clearance (CL/F) of bimekizumab-bkzx was 0.337 L/day (32.7%). The mean terminal elimination half-life was 23 days, with clearance independent of dose. The apparent clearance in subjects with moderate to severe hidradenitis suppurativa was estimated to be approximately 31% higher than in subjects with moderate to severe plaque psoriasis. Metabolism: Bimekizumab-bkzx is expected to be degraded into small peptides by catabolic pathways. Specific Populations No significant differences in the pharmacokinetics of bimekizumab-bkzx were observed based on age (≥18 years). Body Weight: The average plasma concentration in adult subjects weighing ≥120 kg was predicted to be at least 30% lower than those weighing < 120 kg (median of 87 kg) [see Dosage and Administration (2.2) ].