NEMLUVIO- nemolizumab-ilto_injection, powder, lyophilized, for solution

Nemolizumab-ilto is a humanized IgG2 monoclonal antibody that inhibits IL-31 signaling by binding selectively to IL-31 RA. IL-31 is a naturally occurring cytokine that is involved in pruritus, inflammation, epidermal dysregulation, and fibrosis. Nemolizumab-ilto inhibited IL-31-induced responses including the release of proinflammatory cytokines and chemokines After a single dose, nemolizumab-ilto exposure increased dose proportionally over a dose range of 0. 03 and 3 mg/kg following subcutaneous administration. After multiple doses, nemolizumab-ilto systemic exposure increased in an approximately dose-proportional manner across the subcutaneous dose range up to 30 mg. There was a decrease in bioavailability by 9% with the 60 mg subcutaneous dose and by 15% with the 90 mg subcutaneous dose. Following multiple doses of NEMLUVIO in subjects with prurigo nodularis, the estimated mean (SD) steady-state trough concentrations of nemolizumab-ilto were 3. 23) µg/mL in subjects with bodyweight less than 90 kg; and 3. 63) µg/mL in subjects with bodyweight of 90 kg or more. Steady state nemolizumab-ilto concentrations were achieved by week 4 in subjects weighting less than 90 kg and by week 12 in subjects weighing 90 kg or more. Absorption max Distribution Elimination Metabolism Specific Populations Geriatric Populations Renal or Hepatic Impairment Body Weight ss maxss trough Drug Interaction Studies The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of nemolizumab-ilto or other nemolizumab products. In the Phase 3 trials (OLYMPIA 1, OLYMPIA 2) up to 24 weeks, the incidence of treatment-emergent ADAs was 7%; neutralizing antibodies were seen in 3% of subjects. There was no identified clinically significant effect of anti-drug antibodies on the pharmacokinetics, safety or efficacy of nemolizumab-ilto over the treatment duration of 24 weeks.

NEMLUVIO is indicated for the treatment of adults with prurigo nodularis. NEMLUVIO is an interleukin-31 receptor alpha antagonist indicated for the treatment of adults with prurigo nodularis.

DOSAGE AND ADMINISTRATION
Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating treatment with NEMLUVIO, ( 2. 1 Adult Patients Weighing Less Than 90kg 2. 2 Adult Patients Weighing 90kg or More: 2. 2 Administer NEMLUVIO by subcutaneous injection. 4 NEMLUVIO must be reconstituted prior to administration. 5 Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to treatment with NEMLUVIO [see Warnings and Precautions ( 5. 2 Adult Patients Weighing Less Than 90 kg: Adult Patients Weighing 90 kg or More: If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time. NEMLUVIO is administered by subcutaneous injection. NEMLUVIO is intended for use under the guidance of a healthcare provider. Prior to the first injection, provide patients and/or caregivers with proper training on the preparation and administration of NEMLUVIO. Patients may self-inject NEMLUVIO after receiving training on subcutaneous injection techniques. For the initial dose, administer each of the two NEMLUVIO injections at different injection sites. Administer subcutaneous injection into the front upper thighs or abdomen except for the 2 inches (5 cm) around the navel. Injection in upper arm should only be performed by a caregiver or healthcare professional. Alternate the injection site with each injection. Do not inject NEMLUVIO into skin that is tender, inflamed, swollen, damaged or has bruises or scars or open wounds. Refer to the Instructions for Use for complete administration instructions with illustrations [see Instructions for Use Before injection, remove NEMLUVIO carton from the refrigerator and allow to reach room temperature (30-45 minutes). Inspect NEMLUVIO visually prior to reconstitution. NEMLUVIO is supplied in a single-dose pre-filled dual-chamber pen with white powder in one chamber and a clear diluent in the other chamber. Do not use if powder is not white, or if diluent is cloudy or contains visible particles. NEMLUVIO must be reconstituted prior to administration. Following reconstitution, each pre-filled pen delivers 30 mg/0. 49 mL as a clear and colorless to slightly yellow solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the reconstituted solution has discoloration or contains particles. Use NEMLUVIO pens within 4 hours after reconstitution. Discard unused reconstituted NEMOLUVIO pens after 4 hours. Discard any unused portions after administration Refer to the Instructions for Use for complete preparation instructions with illustrations [ see Instructions for Use.
INSTRUCTIONS FOR USE SECTION
NEMLUVIOregistered [Nem LOO vee oh] (nemolizumab-ilto) for injection, for subcutaneous use This Instructions for Use contains information on how to inject NEMLUVIO. Read and understand these instructions before using the NEMLUVIO pen. Important Information What you need to know before using the NEMLUVIO pen: Read all the instructions carefully before using the NEMLUVIO pen. Mark your calendar Follow all steps exactly as described. This makes sure that you get the correct dose of medicine. Make sure that the lyophilized powder is completely dissolved before injecting (Step 9). After dissolving, proceed right away with the injection to avoid any contamination or break down of medicine (degradation). Do not In some cases, your healthcare provider may prescribe 2 pens for a full dose. Use 1 NEMLUVIO pen after the other. To reduce the risk of accidental needle stick injury, each NEMLUVIO pen has an orange needle guard. After injecting the medicine, as you lift the pen from your skin, the orange needle guard locks into place to cover the needle (Step 16). When preparing the pen for injection, do not Throw away (dispose of) the used NEMLUVIO pen right away after use in a sharps disposal container. See Section C: Throwing away (Disposing of) NEMLUVIO below. Storage Information: Store the NEMLUVIO pen in the refrigerator between 36°F to 46°F (2°C to 8°C) until the expiration date. Store the NEMLUVIO pen in the original carton to protect it from light. The NEMLUVIO pen can be stored at room temperature up to 77°F (25°C) for a single period up to 90 days. Thow away (dispose of) the NEMLUVIO pen after the expiration date and any NEMLUVIO pen that has been left at room temperature longer than 90 days. After the NEMLUVIO pen lyophilized powder and water for injection are mixed (reconstituted), the NEMLUVIO pen must be used within 4 hours or thrown away (discarded). Do not Do not If the NEMLUVIO pen was heated or frozen, throw away (dispose of it). Keep the NEMLUVIO pen and all medicines out of the reach of children. Traveling Information: Generally you are allowed to carry pens with you on an airplane. Be sure to carry the NEMLUVIO pens with you in your carry-on luggage A. Preparing to inject NEMLUVIO Step 1: Let NEMLUVIO reach room temperature NEMLUVIO . Do not: warm the pen with any heat source (such as microwave or direct sunlight). This might damage NEMLUVIO. directly expose the pen to liquids. Step 2: Wash your hands Step 3: Gather Supplies Pen Alcohol wipes* Sharps disposal container* Gauze pads or cotton balls* *Items not included in the carton. Step 4: Check the NEMLUVIO pen for the following: not not not Do not not call: 1-866-735-4137 Step 5: Activate the NEMLUVIO pen Step 6: Wait until the gray rod stops moving Do not Step 7: Dissolve the medicine Step 8: Wait 5 minutes for bubbles to decrease Note Step 9: Check the medicine in the inspection window is clear and colorless to slightly yellow, does not contain particles (see Figure i). Do not Note B. Injecting NEMLUVIO Step 10: Select one injection site Note: Where not to inject: near your waistline or about 2 inches around the navel. into tender, bruised, red skin, or areas with scars or stretch marks twice into the same site (example, within, 1 inch). Step 11: Clean the injection site air dry. Do not: touch the injection site after cleaning. fan, or blow air on the cleaned injection site. reuse the alcohol wipe. Step 12: Twist the gray cap Do not: pull the gray cap when twisting to avoid damaging the device. touch the orange needle guard. Hold pen Twist the gray cap until the orange needle guard pops up (see Figure L, b). Gently pull the cap off the orange needle guard (see Figure L, c) After cap removal, please throw away (dispose of) the cap in a sharps disposal container (see Step 17). Note Step 5 Step 13: Place the NEMLUVIO pen Read Steps 13-16 before starting Step 13. Note: Note: Step 14: Start injection and hold the NEMLUVIO pen on the skin Do not Step 15: Inject for 15 seconds . Note: Do not call: 1-866-735-4137. . Do not C. Throwing away (disposing of) NEMLUVIO Step 17: Throw away (dispose of) NEMLUVIO in a sharps disposal container Avoid contact with the needle. Do not: recap the pen after use, dispose of the NEMLUVIO pen and cap in your household trash, dispose of your used sharps disposal container in your household trash unless your community guidelines permit this, recycle your used sharps disposal container. If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: made of a heavy-duty plastic, can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant and properly labeled to warn of hazardous waste inside the container. When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: FAQs (Frequently asked questions) Needle Injecting the medicine Where is the needle? Why do I need to hold the pen upright while removing the gray cap? The needle is attached to the NEMLUVIO pen and covered by the gray cap. Step 12 Holding the NEMLUVIO pen with the gray cap upright helps prevent the medicine from leaking. It is normal to see a few drops of medicine inside the gray cap even when you hold the pen upright and remove the gray cap. Dissolving the medicine How do I know I injected myself the full dose of medicine in the pen? How do I know if the medicine is fully dissolved? To be sure you get the full dose of medicine, press and hold the NEMLUVIO pen against your skin. Step 15 To dissolve, shake the NEMLUVIO pen up and down until the white particles are no longer on the bottom, top, or sides. The dissolved medicine should look clear. Please refer to Step 9 . Storage General Information How should I store the NEMLUVIO pen? Is it necessary to receive instructions on how to use the NEMLUVIO pen from a healthcare provider? The NEMLUVIO pen should be stored in the refrigerator in its original carton to protect it from light. Yes. Do not Where do I find the expiration date? Where can I get more information about using NEMLUVIO: You can find the expiration date on the NEMLUVIO pen, it is labeled EXP YYYY-MM. Do not If you have other questions about how to use the NEMLUVIO pen: What should I do if the medicine has been frozen Do not Manufactured by:

The following clinically significant adverse reactions are described in greater details elsewhere in the labeling: [see Warnings and Precautions (5. 1 Most common adverse reactions (incidence >=1%) are headache, dermatitis atopic, eczema, and eczema nummular. 1 To report SUSPECTED ADVERSE REACTIONS, contact Galderma Laboratories, L. at 1-866-735-4137 or FDA at 1-800-FDA-1088 or www. gov/medwatch. 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. A total of 508 adult subjects with prurigo nodularis were treated with NEMLUVIO in two placebo-controlled trials and an open label long-term extension trial. Of these, 375 subjects were exposed for at least 1 year in the development program for prurigo nodularis. Two randomized, double-blind, placebo-controlled, multicenter trials (OLYMPIA 1 and OLYMPIA 2) evaluated the safety of NEMLUVIO in adult subjects with prurigo nodularis. Subjects were treated for up to 24 weeks in OLYMPIA 1 and up to 16 weeks in OLYMPIA 2. In these 2 trials, 370 subjects were treated with subcutaneous injections of NEMLUVIO, and 186 subjects received placebo injections [ see Clinical Studies (14) Subjects weighing less than 90 kg in the NEMLUVIO group received NEMLUVIO 60 mg or placebo at Week 0, followed by 30 mg injections every 4 weeks. Subjects weighing 90 kg or more in the NEMLUVIO group received NEMLUVIO 60 mg or placebo at Week 0 and every 4 weeks. During the treatment period in NEMLUVIO trials (OLYMPIA 1 and OLYMPIA 2), the proportion of subjects who discontinued treatment because of adverse reactions was 4% in NEMLUVIO group versus 3% in the placebo group. Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% in the NEMLUVIO group, and for which the rate exceeds the rate in the placebo group through Week 16. Table 1: Adverse Reactions Occurring in >=1% of Adult Subjects with Prurigo Nodularis in the NEMLUVIO Group and Greater than Placebo in the OLYMPIA 1 and OLYMPIA 2 Trials through Week 16. *includes: headache and tension headache Adverse Reaction NEMLUVIO N= 370 n (%) Placebo (N= 186) n (%) Headache* 23 (6%) 6 (3%) Dermatitis atopic 16 (4%) 1 (0. 5%) Eczema 14 (4%) 3 (2%) Eczema nummular 11 (3%) 0 Specific Adverse Reactions Hypersensitivity reactions [ see Contraindications (4).

NEMLUVIO is contraindicated in patients who have known hypersensitivity to nemolizumab-ilto or to any of the excipients in NEMLUVIO [ see Warnings and Precautions (5. 1) Known hypersensitivity to nemolizumab-ilto or to any of the excipients in NEMLUVIO.

Risk Summary see Clinical Considerations see Data Clinical Considerations Fetal/Neonatal Adverse Reactions Data Animal Data Risk Summary see Data Data The safety and effectiveness of NEMLUVIO have not been established in pediatric patients. Of the 370 subjects with prurigo nodularis exposed to NEMLUVIO in OLYMPIA 1 and OLYMPIA 2, 99 (26. 8%) subjects were 65 years of age or older. The long-term safety of NEMLUVIO was assessed in 508 subjects, among which 133 (26. 2%) were 65 years of age or older. Clinical trials of NEMLUVIO did not include sufficient number of subjects 65 years of age or older to determine whether they respond differently than younger adult subjects [ see Clinical Pharmacology (12.

OVERDOSAGE
There is no specific treatment for NEMLUVIO overdose. In the event of overdosage, contact Poison Control (1-800-222-1222) for the latest recommendations and monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.
NONCLINICAL TOXICOLOGY
Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of NEMLUVIO.
CLINICAL STUDIES
Two randomized, double-blind, placebo-controlled trials (OLYMPIA 1 [NCT04501666 ] Subjects weighing less than 90 kg in the NEMLUVIO group received subcutaneous injections of NEMLUVIO 60 mg at Week 0, followed by 30 mg injections every 4 weeks. Subjects weighing 90 kg or more in the NEMLUVIO group received subcutaneous injections of NEMLUVIO 60 mg at Week 0 and every 4 weeks. In these trials, at baseline, 60% of subjects were female, 81% were White, 9% were Asian, 7% were Black or African American; for ethnicity, 4% of subjects identified as Hispanic or Latino. Twenty five (25)% of subjects were older than 65 years of age. Thirty-two (32)% of subjects had a history of atopy. The baseline weekly average PP-NRS score was a mean of 8.5. Fifty-eight (58)% of subjects had a baseline IGA score of 3 (moderate PN), and 42% of subjects had a baseline IGA of 4 (severe PN). The PP-NRS score is a weekly average of daily PP-NRS scores on an 11-point scale from 0-10 that assesses the maximal intensity of pruritus in the last 24 hours with 0 being no itch and 10 being worst itch imaginable. The IGA is a 5-category scale, including “0 = clear”, “1 = almost clear”, “2 = mild”, “3 = moderate” or “4 = severe” indicating the investigator’s overall assessment of the pruriginous nodules. Efficacy was assessed with the proportion of subjects with an improvement of >=4 from baseline in PP-NRS, the proportion of subjects with an IGA of 0 (Clear) or 1 (Almost Clear) and a >=2-point improvement from baseline, the proportion of subjects who achieved a response in both PP-NRS and IGA per the criteria described above, and the proportion of subjects with PP-NRS <2. The efficacy results for OLYMPIA 1 and OLYMPIA 2 are presented in Table 2 and Figures 1, 2, and 3. Table 2: Efficacy Results at Week 16 in Adult Subjects with PN in OLYMPIA1 and OLYMPIA 2 a b OLYMPIA 1 OLYMPIA2 NEMLUVIO Placebo Difference from Placebo NEMLUVIO Placebo Difference from Placebo Proportion of subjects with both an improvement (reduction) of >=4 from baseline in PP-NRS and IGA 0 or 1 a,b 22% a 2% a 15% a 25% a 4% a 22% a Proportion of subjects with IGA 0 or 1 b 26% 7% 15% 38% 11% 29% Proportion of subjects with an improvement (reduction) of >=4 from baseline in PP-NRS b 56% 16% 38% 49% 16% 34% Proportion of subjects with PP-NRS <2 b 32% 4% 28% 31% 7% 26% Figure 1: Proportion of Adult Subjects with PN with PP-NRS Improvement >=4 from Baseline Over Time in OLYMPIA 1 and OLYMPIA 2 a a Figure 2: Proportion of Adult Subjects with PN with PP-NRS <2 Over Time in OLYMPIA 1 and OLYMPIA 2 a a Figure 3: Proportion of Adult Subjects with PN with IGA Response a b a b Examination of weight, age, gender, race, history of atopy, and prior treatment did not identify meaningful differences in response to NEMLUVIO among these subgroups at Week 16.

Galderma Laboratories, L.P.

NEMLUVIO- nemolizumab-ilto_injection, powder, lyophilized, for solution Product manual source documgent