Bimzelx Drug Information

Plaque Psoriasis BIMZELX is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

Psoriatic Arthritis BIMZELX is indicated for the treatment of adults with active psoriatic arthritis.

Non-Radiographic Axial Spondyloarthritis BIMZELX is indicated for the treatment of adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation.

Ankylosing Spondylitis BIMZELX is indicated for the treatment of adults with active ankylosing spondylitis.

Hidradenitis Suppurativa BIMZELX is indicated for the treatment of adults with moderate to severe hidradenitis suppurativa.

Recommended Evaluations and Immunization Prior to Treatment Initiation Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with BIMZELX. Test liver enzymes, alkaline phosphatase and bilirubin prior to initiating treatment with BIMZELX. Complete all age-appropriate vaccinations as recommended by current immunization guidelines.

Recommended Dosage for Plaque Psoriasis

The recommended dosage is 320 mg by subcutaneous injection at Weeks then every 8 weeks thereafter. For psoriatic arthritis patients with coexistent moderate to severe plaque psoriasis, use the dosing regimen for adult patients with plaque psoriasis.

Recommended Dosage for Non-Radiographic Axial Spondyloarthritis The recommended dosage is 160 mg by subcutaneous injection every 4 weeks.

Missed Doses If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regularly scheduled interval.

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.

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".

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.

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. A total of 670 subjects were treated during this initial period with BIMZELX 320 mg at Weeks 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 7 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.

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)). 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%). The completed suicide was reported in a subject without a past reported psychiatric history.

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 ) 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. 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. 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). Specific Adverse Reactions Suicidal Ideation and Behavior: The neuropsychiatric inclusion/exclusion criteria in PsA trials were the same as in PSO. 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). 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.

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%)). 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. There were no reports of serious infections reported during the placebo-controlled period of the trial.

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. 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%)). Liver Biochemical Abnormalities: During the placebo-controlled period of Trial AS-1, liver serum transaminase elevations (> 3 times the upper limit of normal ) occurred in 1.4% of subjects treated with BIMZELX versus 1.8% of subjects receiving placebo. 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).

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. 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. The most commonly reported infections were comparable to those reported in subjects with PSO. 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).

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.

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

CYP450 Substrates The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation. Treatment with BIMZELX may modulate serum levels of some cytokines. Therefore, upon initiation or discontinuation of BIMZELX in patients who are receiving concomitant drugs which are CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for effect (e.g., for warfarin) or drug concentration (e.g., for cyclosporine) and consider dosage modification of the CYP450 substrate.

Population pharmacokinetic (PK) data analyses indicated that the clearance of BIMZELX was not impacted by concomitant administration of cDMARDs including methotrexate, or by prior exposure to biologics.

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to BIMZELX during pregnancy. For more information, healthcare providers or patients can contact the Organization of Teratology Information Specialists (OTIS) AutoImmune Diseases Study at 1-877-311-8972 or visit http://mothertobaby.org/pregnancy-studies/. Risk Summary Available data from case reports on BIMZELX use in pregnant women are insufficient to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Transport of human IgG antibody across the placenta increases as pregnancy progresses and peaks during the third trimester; therefore, BIMZELX may be transmitted from the mother to the developing fetus (see Clinical Considerations ). In an enhanced pre- and postnatal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of bimekizumab-bkzx during the period of organogenesis through parturition at doses up to 38 times the maximum recommended human dose (MRHD) (see Data ). All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions: Because bimekizumab-bkzx may interfere with immune response to infections, risks and benefits should be considered prior to administering live vaccines to infants exposed to BIMZELX in utero.

There are no data regarding infant serum levels of bimekizumab-bkzx at birth and the duration of persistence of bimekizumab-bkzx in infant serum after birth. Although a specific timeframe to delay live virus immunizations in infants exposed in utero is unknown, a minimum of 4 months after birth may be considered because of the half-life of the product. Data Animal Data: An enhanced pre- and postnatal developmental toxicity study was conducted in cynomolgus monkeys.

Pregnant cynomolgus monkeys were administered subcutaneous doses of bimekizumab-bkzx of 20 or 50 mg/kg/week from gestation day 20 to parturition and the cynomolgus monkeys (mother and infants) were monitored for 6 months after delivery. No maternal toxicity was noted in this study. There were no treatment-related effects on growth and development, malformations, developmental immunotoxicology or neurobehavioral development.

Pediatric Use The safety and effectiveness of BIMZELX in pediatric patients have not been established.