Nemluvio

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

For injection: single-dose pre-filled 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.

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

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.

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, pre-filled 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 pre-filled pen delivers 30 mg/0.49 mL of nemolizumab-ilto with a pH of 6.7 to 7.3.

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.
b Subjects 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.

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

Each carton contains 1 single-dose pre-filled pen:

Storage and Handling
Store the NEMLUVIO dual-chamber pre-filled 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 pre-filled 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 pre-filled 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 pre-filled pen beyond the expiration date or 90 days after the date it was first removed from the refrigerator (whichever is earlier).

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 and slowly 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 an 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
U.S. License No. 2289
Issued: 08/2024

P502292-0

 Mechanism of Action

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