Nemluvio Prescribing Information

1. Indications and Usage for Nemluvio

NEMLUVIO is indicated for the treatment of adults with prurigo nodularis.

2. Nemluvio Dosage and Administration

3. Dosage Forms and Strengths

For injection: single-dose prefilled dual-chamber pen containing 30 mg of nemolizumab-ilto as a white lyophilized powder in one chamber and diluent, water for injection, in the other chamber.

4. Contraindications

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)].

5. Warnings and Precautions

6. Adverse Reactions/Side Effects

The following clinically significant adverse reactions are described in greater details elsewhere in the labeling:
Hypersensitivity [see Warnings and Precautions (5.1)]

7. Drug Interactions

Cytochrome P450 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 NEMLUVIO may modulate serum levels of some cytokines and influence the formation of CYP450 enzymes.

Therefore, upon initiation or discontinuation of NEMLUVIO 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.

8. Use In Specific Populations

10. 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.

11. Nemluvio Description

Nemolizumab-ilto, an interleukin-31 receptor alpha (IL-31RA) antagonist, is a humanized monoclonal modified immunoglobulin G (IgG) antibody with a molecular weight of approximately 144 kDa. Nemolizumab-ilto is produced by recombinant DNA technology in Chinese Hamster Ovary cells.

NEMLUVIO (nemolizumab-ilto) for injection is a sterile, preservative-free, white lyophilized powder in a dual-chamber single-dose, prefilled pen. One chamber contains 30 mg of nemolizumab-ilto with inactive ingredients arginine hydrochloride (9.5 mg), poloxamer 188 (0.15 mg), sucrose (25.8 mg), trometamol (0.10 mg), and tris hydrochloride for pH adjustment. The diluent, water for injection, is in the other chamber. Following reconstitution, each prefilled pen delivers 30 mg/0.49 mL of nemolizumab-ilto with a pH of 6.7 to 7.3.

12. Nemluvio - Clinical Pharmacology

13. Nonclinical Toxicology

14. Clinical Studies

Two randomized, double-blind, placebo-controlled trials (OLYMPIA 1 [NCT04501666] and OLYMPIA 2 [NCT04501679]) enrolled a total of 560 adult subjects with prurigo nodularis (PN). Disease severity was defined using an Investigator’s Global Assessment (IGA) in the overall assessment of prurigo nodularis nodules on a severity scale of 0 to 4. Subjects enrolled in these two trials had an IGA score ≥ 3, severe pruritus as defined by a weekly average of the peak pruritus numeric rating scale (PP-NRS) score of ≥7 on a scale of 0 to 10, and greater than or equal to 20 nodular lesions. OLYMPIA 1 and OLYMPIA 2 assessed the effect of NEMLUVIO on the signs and symptoms of PN, targeting improvement in skin lesions and pruritus over 16 weeks. In OLYMPIA 1, subjects were extended up to 24 weeks of treatment.

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.

Figure 1: Proportion of Adult Subjects with PN with PP-NRS Improvement ≥4 from Baseline Over Time in OLYMPIA 1 and OLYMPIA 2a

a Subjects who received rescue therapy or had missing data (fewer than 4 PP-NRS daily diary entries in a 7-day period) were considered non-responders.

Figure 2: Proportion of Adult Subjects with PN with PP-NRS <2 Over Time in OLYMPIA 1 and OLYMPIA 2a

a Subjects who received rescue therapy or had missing data (fewer than 4 PP-NRS daily diary entries in a 7-day period) were considered non-responders.

Figure 3: Proportion of Adult Subjects with PN with IGA Responsea Over Time in OLYMPIA 1 and OLYMPA 2b

a Response was defined as an IGA of 0 (Clear) or 1 (Almost Clear) and a ≥2-point improvement from baseline.
bSubjects who received rescue therapy or had missing data were considered non-responders.

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.

16. How is Nemluvio supplied

How Supplied
NEMLUVIO (nemolizumab-ilto) for injection is a sterile, preservative-free, white lyophilized powder available in a single-dose, dual chamber prefilled pen containing 30 mg of nemolizumab-ilto in one chamber and the diluent, water for injection, in the other chamber. Following reconstitution, each prefilled pen delivers 30 mg/0.49 mL of nemolizumab-ilto.

Each carton contains 1 single-dose prefilled pen:

Storage and Handling
Store the NEMLUVIO dual chamber prefilled pen in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light until the expiration date. Do not freeze. Do NOT expose to heat or direct sunlight.

Alternatively, the NEMLUVIO carton containing the unused dual chamber prefilled pen may be stored at room temperature [up to 77°F (25°C)] for up to 90 days. Write the date the NEMLUVIO dual chamber prefilled pen is first removed from the refrigerator in the space provided on the inner partition for the pen. Do not use the NEMLUVIO dual chamber prefilled pen beyond the expiration date or 90 days after the date it was first removed from the refrigerator (whichever is earlier).

17. Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Hypersensitivity
Advise patients to seek immediate medical attention and discontinue NEMLUVIO if they experience any symptoms of hypersensitivity reactions [see Warnings and Precautions (5.1)].

Vaccinations
Instruct patients to inform their healthcare provider that they are taking NEMLUVIO prior to a potential vaccination [see Warnings and Precautions (5.2)].

Administration Instructions:

• Instruct patients and/or caregivers to receive proper training in subcutaneous injection technique prior to self-injection [see Dosage and Administration (2.4)]. Inform patients and/or caregivers that Galderma Customer Support may be called toll-free for assistance at 1-866-735-4137.
• Inform patients that NEMLUVIO must be reconstituted prior to administration. Advise patients and/or caregivers to refer to the Instructions for Use that accompanies the NEMLUVIO pen for complete mixing and administration instructions with illustrations [see Dosage and Administration (2.4, 2.5), Instructions for Use].
• Inform patients and/or caregivers of proper pen disposal and caution against any reuse of needles. Instruct patients and/or caregivers to discard used pens in an appropriate sharps disposal container following safe needle disposal practices [see Instructions for Use].
• Advise patients/caregivers of the importance of complying with dosing schedule. If a dose is missed, instruct patients and/or caregivers to administer the injection as soon as possible, and thereafter, resume dosing at the regular scheduled time. [see Dosage and Administration (2.3)].
  

PATIENT INFORMATION

NEMLUVIO® [Nem LOO vee oh]
(nemolizumab-ilto)
for injection, for subcutaneous use

What is NEMLUVIO?

• NEMLUVIO is a prescription medicine used to treat adults with prurigo nodularis.

It is not known if NEMLUVIO is safe and effective in children under 18 years of age.

Do not take NEMLUVIO if you are allergic to nemolizumab-ilto or to any ingredients in NEMLUVIO. See the end of this Patient Information leaflet for a complete list of ingredients in NEMLUVIO.

Before taking NEMLUVIO, tell your healthcare provider about all of your medical conditions, including if you:

• are scheduled to receive any vaccination. You should not receive a live vaccine right before or during treatment with NEMLUVIO.
• are pregnant or plan to become pregnant. It is not known whether NEMLUVIO will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known whether NEMLUVIO passes into your breast milk and if it can harm your baby.

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I take NEMLUVIO?

• See the detailed Instructions for Use that comes with NEMLUVIO for information on how to prepare and inject NEMLUVIO and how to properly store and throw away (dispose of) used NEMLUVIO prefilled pens.
• Use NEMLUVIO exactly as prescribed by your healthcare provider.
• Your healthcare provider will tell you how much NEMLUVIO to inject and how often to inject it.
• NEMLUVIO comes as a single-dose prefilled pen with a needle guard.
• NEMLUVIO is given as an injection under the skin (subcutaneous injection).
• If your healthcare provider decides that you or a caregiver can give the injections of NEMLUVIO, you or your caregiver should receive training on the right way to prepare and inject NEMLUVIO. Do not try to inject NEMLUVIO until you have been shown the right way by your healthcare provider.
• If you miss a dose, inject the missed dose as soon as possible, then continue with your next dose at your regular scheduled time.
• If you inject too much NEMLUVIO , call your healthcare provider or the Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.
• Your healthcare provider may prescribe other medicines to use with NEMLUVIO. Use the other prescribed medicines exactly as your healthcare provider tells you to.
  

What should I avoid while taking NEMLUVIO?
You should not receive live vaccines while taking NEMLUVIO.

What are the possible side effects of NEMLUVIO?
NEMLUVIO may cause serious side effects, including:

allergic reactions (hypersensitivity). NEMLUVIO can cause allergic reactions that can sometimes be serious. Stop using NEMLUVIO and tell your healthcare provider or get emergency help right away if you get any of the following symptoms:

The most common side effects of NEMLUVIO include:

• headache
• skin rashes: atopic dermatitis (a type of eczema), eczema, and eczema nummular (scattered circular patches)

These are not all of the possible side effects of NEMLUVIO.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store NEMLUVIO?

• Store NEMLUVIO in the refrigerator between 36°F to 46°F (2°C to 8°C) until the expiration date.
• Store NEMLUVIO in the original carton to protect from light.
• NEMLUVIO can be stored at room temperature up to 77°F (25°C) for a single period of up to 90 days.
• Throw away (dispose of) NEMLUVIO after the expiration date and any NEMLUVIO that has been left at room temperature for longer than 90 days.
• After NEMLUVIO lyophilized powder and water for injected are mixed (reconstituted), NEMLUVIO must be used within 4 hours or thrown away (discarded).
• Do not heat or put NEMLUVIO into direct sunlight.
• Do not freeze NEMLUVIO.
• If NEMLUVIO was heated or frozen, throw it away (dispose of it).

Keep NEMLUVIO and all medicines out of the reach of children.

General information about the safe and effective use of NEMLUVIO.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use NEMLUVIO for a condition for which it was not prescribed. Do not give NEMLUVIO to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about NEMLUVIO that is written for healthcare professionals.

What are the ingredients in NEMLUVIO?
Active ingredient: nemolizumab-ilto
Inactive ingredients: arginine hydrochloride, poloxamer 188, sucrose, trometamol, and tris hydrochloride.

Manufactured by: Galderma Laboratories, L.P., Dallas, TX 75201
U.S. License No. 2289
NEMLUVIO® is a trademark of Galderma.
© #### Galderma Laboratories, L.P. All rights reserved.
For more information, go to www.NEMLUVIO.com or call 1-866-735-4137.

This Patient Information has been approved by the U.S. Food and Drug Administration.
Issued: 08/2024

INSTRUCTIONS FOR USE

NEMLUVIO® [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.

Do not inject yourself or someone else until you have been instructed how to inject NEMLUVIO.

Your healthcare provider will instruct you or your caregiver how to prepare and inject a dose of NEMLUVIO before you try to do it yourself the first time. Call your healthcare provider if you have any questions.

NEMLUVIO is supplied as a single-dose pen (called NEMLUVIO pen or pen in these instructions). It contains medicine (30 mg of lyophilized powder) in one chamber and water for dissolving the medicine in the other chamber. Before you can inject it, you must mix the lyophilized powder with the water for dissolving the medicine.

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 ahead of time to remember when to take NEMLUVIO.
• 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 use the NEMLUVIO pen if it has been dropped on a hard surface or is damaged, cracked or broken.
• 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 pull the gray cap. Instead, twist the gray cap until the orange needle guard pops up. Then, gently pull the cap off the orange needle guard (Step 12).
• 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 heat or put the NEMLUVIO pen into direct sunlight.
• Do not freeze the NEMLUVIO pen.
• 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
  
  If you have any other questions refer to the Frequently asked questions (FAQs) on the back of this leaflet.

A. Preparing to inject NEMLUVIO

Step 1: Let NEMLUVIO reach room temperature
Injecting cold medicine might result in pain at the injection site.
Take the NEMLUVIO carton out of the refrigerator and let it come to room temperature for 30 to 45 minutes before starting Step 2 (see Figure A).

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
a. To avoid contamination and infection, wash your hands with soap (see Figure B).
b. Dry them properly.

Step 3: Gather Supplies (see Figure C)
a. Remove the pen from the carton.
b. Gather the following supplies on a clean, flat and well-lit surface:

1. Pen
2. Alcohol wipes*
3. Sharps disposal container*
4. Gauze pads or cotton balls*

*Items not included in the carton.

Note: In some cases, your healthcare provider may prescribe 2 pens. Use 1 pen after the other.

Step 4: Check the NEMLUVIO pen for the following:
a. Expiration date has not passed.
b. The lyophilized powder is white and not dissolved (see Figure D).
c. The pen has not been dropped and is not damaged or cracked.



Do not use the pen, unless all conditions above are met.
If any condition is not met, call: 1-866-735-4137.

Throw away (dispose of) the pen and use a new one (see Section C: Throwing away (Disposing of) NEMLUVIO).

Step 5: Activate the NEMLUVIO pen
Hold the pen upright and turn activation knob to the right until it stops (see Figure E).
This starts the process of transferring water to the powder chamber.

Step 6: Wait until the gray rod stops moving
Watch inspection window until gray rod has stopped moving (see Figure F).


Do not shake the pen. Shaking the pen before the gray rod has completely stopped can affect the medicine dose.

Step 7: Dissolve the medicine
When the gray rod has completely stopped, shake the pen up and down for 30 seconds (see Figure G).

Step 8: Wait 5 minutes for bubbles to decrease
Wait for bubbles to decrease and the lyophilized powder to dissolve completely. This will take about 5 minutes (see Figure H).



Note: If the medicine has not dissolved completely, shake the pen up and down again for 30 seconds and then wait 5 minutes.
Note: It is normal for a small foam layer or a few small air bubbles to remain in the dissolved medicine.

Step 9: Check the medicine in the inspection window
Check to see if the dissolved medicine:

1. is clear and colorless to slightly yellow,
2. does not contain particles (see Figure i).
   
   
   
   

Do not use the pen if the dissolved medicine is cloudy or contains any particles.

Throw away (dispose of) the pen and use a new one (see Section C: Throwing away (Disposing of) NEMLUVIO).

Note: After the medicine has dissolved, it must be used within 4 hours. During this time, it should be kept at room temperature (up to 77°F (25°C)). If you have not used it within 4 hours, throw it away (dispose of it).

B. Injecting NEMLUVIO

Step 10: Select one injection site (see Figure J)

Note: When using a second pen, select a different injection site at least 1 inch away from the first injection site.

Select the injection site using the following chart:

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 (see Figure K)
a. Always use a new alcohol wipe to clean the injection site.
This avoids contamination and infection.
b. Let the skin 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.

1. Hold the pen upright (see Figure L, a)
2. Twist the gray cap until the orange needle guard pops up (see Figure L, b).
3. Gently pull the cap off the orange needle guard (see Figure L, c)
4. After cap removal, please throw away (dispose of) the cap in a sharps disposal container (see Step 17).

Note: If the cap cannot be removed, refer back to Step 5 and make sure the activation knob is turned completely to the right until it stops.

Step 13: Place the NEMLUVIO pen

Read Steps 13-16 before starting Step 13.

Note: Always inject the way your healthcare provider showed you.

Place the pen on the injection site vertically so that the orange needle guard is flat against the skin (see Figure M).

Note: Make sure you can easily see the inspection window during injection.

Step 14: Start injection and hold the NEMLUVIO pen on the skin

Gently push the pen down until the orange needle guard is completely pushed in.

The injection starts right away with a click (see Figure N).

The orange rod will begin to move down the injection window.

Do not lift the pen yet and keep pushing down.

Step 15: Inject for 15 seconds

Hold slowly and count to 15.

Check inspection window to make sure the orange rod and the gray rod have stopped (see Figure O).
This means the injection has been completed.

Note: It is normal that the orange rod does not cover the whole inspection window at the end of injection.



Do not lift the pen until the orange rod and gray rod have stopped moving.

If the orange rod is not visible please call: 1-866-735-4137. Throw away (dispose of) the pen and use a new one (see Section C for disposal details).

Step 16: Lift the NEMLUVIO pen up
a. Lift the pen straight up from your skin.
The orange needle guard locks into place to cover the needle (see Figure P).
b. If there is bleeding, press a cotton ball or gauze over the injection site.



Do not rub the injection site.

C. Throwing away (disposing of) NEMLUVIO

Step 17: Throw away (dispose of) NEMLUVIO in a sharps disposal container

Avoid contact with the needle.

Throw away (dispose of) the used pen and the gray cap in a FDA cleared sharps disposal container right away after use (see Figure Q).



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.
There may be state or local laws about how you should dispose of used pens.

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:
http://www.fda.gov/safesharpsdisposal

FAQs (Frequently asked questions)

Manufactured by:
Galderma Laboratories, L.P.
Dallas, TX 75201
This Instructions for Use has been approved by the U.S. Food and Drug Administration
US License No. 2289
Issued: 08/2024

PRINCIPAL DISPLAY PANEL 30 mg PRE-FILLED DUAL-CHAMBER PEN CARTON

IMPORTANT:
CAREFULLY read and follow Instructions for Use.
This pen requires specific steps before injection.

1 Single-Dose Pre-Filled Dual-Chamber Pen

Keep out of reach of children. Do NOT use after expiration.
Do NOT use if seal is broken or damaged. Dosage: See Prescribing

For Subcutaneous Use
MUST BE RECONSTITUTED BEFORE INJECTION
Single-Dose only

GALDERMA

NDC 0299-6220-15 Rx only

nemluvio™
(nemluvio-ilto) for injection 30 mg