DRUG INTERACTIONS-                                                                                                 

  CYP450 Substrates The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL6, IL-10, TNFa, 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.

BRIEF SUMMARY

BIMEKIZUMAB- (Oct 2023)

Indn-    to treat moderate to stherapyevere plaque psoriasis in adults who are candidates for systemic therapy or phototherapy  

Comp-   Injection: 160 mg/mL in a single-dose prefilled syringe or single-dose prefilled autoinjector.   • Administer 320 mg (two 160 mg injections) by subcutaneous injection at Weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing = 120 kg, consider a dose of 320 mg every 4 weeks after Week 16.

ADR-   Most common adverse reactions (= 1%) are upper respiratory tract infections, oral candidiasis, headache, injection site reactions, tinea infections, gastroenteritis, Herpes simplex infections, acne, folliculitis, other candida infections, and fatigue.

CI-   • Suicidal Ideation and Behavior (SI/B): May increase risk of SI/B. Advise patients, their caregivers, and families to monitor for the emergence or worsening of depression, suicidal ideation, or other mood changes.

If such changes occur, advise them to promptly seek medical attention or call theNational Suicide and Crisis Lifeline at 988. Carefully weigh risks and benefits of treatment with BIMZELX in patients with a history of severe depression and/or suicidal ideation or behavior.

 Pat Inform-

 Instruct patients or caregivers to perform the first self-injection under the supervision and guidance of a qualified healthcare professional for proper training in subcutaneous injection technique

 Instructions for Use]. Instruct patients or caregivers to administer two 160 mg single-dose syringes or two 160 mg single-dose autoinjectors to achieve the 320 mg dose of BIMZELX 

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U.S.  APPROVED DRUGS DURING 2023                                        

Serial No 43

Name-          BIMZELX

Active ingedient-        Bimekizumab                      

Indication              to treat moderate to stherapyevere plaque psoriasis in adults who are candidates for systemic therapy or phototherapy                                                                                 

Date  of approval       10/17/2023 

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use BIMZELX safely and effectively.

See full prescribing information for BIMZELX. BIMZELX® (bimekizumab-bkzx) injection, for subcutaneous use

Initial U.S. Approval: 2023

INDICATIONS AND USAGE-

 BIMZELX is a humanized interleukin-17A and F antagonist indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

ADVERSE REACTIONS-

 Most common adverse reactions (= 1%) are upper respiratory tract infections, oral candidiasis, headache, injection site reactions, tinea infections, gastroenteritis, Herpes simplex infections, acne, folliculitis, other candida infections, and fatigue.

CONTRAINDICATIONS-

 None.

WARNINGS AND PRECAUTIONS-

 • Suicidal Ideation and Behavior (SI/B): May increase risk of SI/B. Advise patients, their caregivers, and families to monitor for the emergence or worsening of depression, suicidal ideation, or other mood changes.

 • Infections: May increase risk of infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If such an infection develops, do not administer BIMZELX until the infection resolves.

 • Tuberculosis (TB): Avoid use in patients with active TB. Initiate treatment of latent TB prior to BIMZELX treatment

 • Liver Biochemical Abnormalities: Elevated serum transaminases were reported in clinical trials. Test liver enzymes, alkaline phosphatase, and bilirubin at baseline and according to routine patient management. Permanently discontinue use of BIMZELX in patients with causally - associated combined elevations of transaminases and bilirubin.

 • Inflammatory Bowel Disease (IBD): Cases of IBD were reported in clinical trials with IL-17 inhibitors, including BIMZELX. Avoid use of BIMZELX in patients with active IBD. Monitor patients for signs and symptoms of IBD and discontinue treatment if new onset or worsening of signs and symptoms occurs.

DOSAGE AND ADMINISTRATION-

 • Prior to treatment:

 o Evaluate patients for tuberculosis infection. o Test liver enzymes, alkaline phosphatase, and bilirubin. o Complete all age-appropriate vaccinations as recommended by current immunization guidelines.

• Administer 320 mg (two 160 mg injections) by subcutaneous injection at Weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing = 120 kg, consider a dose of 320 mg every 4 weeks after Week 16.

DOSAGE FORMS AND STRENGTHS-

 Injection: 160 mg/mL in a single-dose prefilled syringe or single-dose prefilled autoinjector. 

 PATIENT COUNSELING INFORMATION-

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Administration Instructions-                                                                                     Instruct patients or caregivers to perform the first self-injection under the supervision and guidance of a qualified healthcare professional for proper training in subcutaneous injection technique

 Instructions for Use]. Instruct patients or caregivers to administer two 160 mg single-dose syringes or two 160 mg single-dose autoinjectors to achieve the 320 mg dose of BIMZELX 

Instruct patients or caregivers in the technique of needle and syringe disposal 

Advise patients if they forget to take their dose of BIMZELX to inject their dose as soon as they remember. Instruct patients to then take their next dose at the appropriate scheduled time 

Suicidal Ideation and Behavior-                                                                                 Instruct patients and their caregivers to monitor for the emergence of suicidal ideation and behavior and promptly seek medical attention if the patient experiences suicidal ideation or behavior; or new onset or worsening depression, anxiety, or other mood changes.

Instruct patients to call the National Suicide and Crisis Lifeline at 988 if they experience suicidal ideation or behavior. 

Infections-  Inform patients that BIMZELX may lower the ability of their immune system to fight infections.

Instruct patients of the importance of communicating any history of infections to the healthcare provider and contacting their healthcare provider if they develop any symptoms of an infection 

Liver Biochemical Abnormalities-                                                                                  Inform patients that BIMZELX may increase the risk of elevated liver enzymes. Acute liver disease or cirrhosis may increase this risk.

Advise patients that laboratory evaluation is needed prior to and periodically during treatment.

Advise patients to hold the next dose of BIMZELX and call their healthcare provider right away, if signs or symptoms of liver dysfunction occur. 

Inflammatory Bowel Disease -                                                                                    Instruct patients to seek medical advice if they develop signs and symptoms of Crohn’s disease or ulcerative colitis 

Immunizations- Advise patients that vaccination with live vaccines is not recommended during BIMZELX treatment. Instruct patients to inform their healthcare practitioner that they are taking BIMZELX prior to a potential vaccination.

Pregnancy-  Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to BIMZELX during pregnancy .

Manufactured by: UCB, Inc. 1950 Lake Park Drive Smyrna, GA 30080 US License No. 1736

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                        Bimekizumab-bkzx is a humanized immunoglobulin IgG1/ ? monoclonal antibody with two identical antigen binding regions that selectively bind to human interleukin 17A (IL-17A), interleukin 17F (IL17F), and interleukin 17-AF cytokines, and inhibits their interaction with the IL-17receptor complex.

2 Pharmacodynamics-                                                                                                Elevated levels of IL-17A and IL-17F are found in lesional psoriatic skin. Bimekizumab-bkzx exposureresponse relationships to serum biomarkers, including IL-17A and IL-17F, and the time course of such pharmacodynamic responses are unknown.

The effectiveness of inactivated seasonal influenza vaccines and other inactivated and non-live vaccines has not been evaluated in patients treated with BIMZELX.

3. Pharmacokinetics-                                                                                                        The following pharmacokinetic parameters are reported for adult patients with moderate to severe plaque psoriasis, unless otherwise specified.

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.

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.

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.

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) 

Immunogenicity-                                                                                                           The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay.

Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of BIMZELX or of other bimekizumab products.

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Pregnancy -                                                                                             Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to BIMZELX during pregnancy.

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

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 2% to 4% and 15% to 20%, respectively.

2. Lactation Risk Summary-                                                                                               There are no data on the presence of bimekizumab-bkzx in human or animal milk, the effects on the breastfed infant, or the effects on milk production..

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for BIMZELX and any potential adverse effects on the breastfed infant from BIMZELX or from the underlying maternal condition.

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

4. Geriatric Use Of the 1789 subjects with plaque psoriasis that were exposed to BIMZELX, a total of 153 subjects were 65 years of age or older, and 18 subjects were 75 years of age or older.

Although no differences in safety or effectiveness were observed between subjects 65 years of age or older and younger adult subjects, the number of subjects aged 65 years and over is not sufficient to determine whether they respond differently from younger adult subjects.