Effective Date

Date of Origin   

04-01-2025           

04-01-2025

Nemluvio®

(nemolizumab-ilto)

Subcutaneous injection

Treatment of adults with prurigo nodularis

1

Prurigo Nodularis (PN)

Prurigo nodularis (PN) is a skin disorder that is defined by the presence of chronic pruritus and multiple elevated, firm, and nodular lesions. PN is more common in older adults but can occur in children. The underlying cause of PN is unknown, but it appears neural and immunologic processes both play a role in its development. The nodules form in a subset of patients that have chronic pruritus, with the nodules forming in areas with continuous scratching over prolonged periods of time. There is significant disease burden associated with PN including sleep disruption, anxiety, and depression. The nodules are typically firm, dome-shaped, and itchy and range in size from millimeters to several centimeters. The nodules can range in color from flesh tones to brown/black and can range in number from a few to hundreds. The pruritis associated with PN can range from sporadic to continuous, and generally the underlying cause is unknown. There are a number of conditions, both dermatologic and other diseases, that are associated with PN, such as atopic dermatitis, kidney disease, diabetes, and HIV.(2)

The diagnosis of PN is generally one of exclusion. The American Academy of Dermatology (AAD) indicates that the diagnostic workup should include a clinical examination with a complete review of systems and assessment of PN severity, which should include both disease burden (e.g., quality of life, sleep disturbances) and pruritis intensity. The AAD notes three core features associated with PN:(2)

• Presence of firm, nodular lesions
• Pruritus that lasts for at least 6 weeks
• History and/or signs of repeated scratching, picking, or rubbing

Management requires a multifaceted approach with a focus on reducing pruritis, interrupting the itch-scratch cycle, and healing lesions.(2) General measures that should be used at baseline include gentle skin care, moisturizers, and antipruritic emollients.(2,3) Treatment may need to address both the neural and immunologic components of pruritis based on patient signs and symptoms, and often involves the use of topical and systemic therapies.(4) Most therapies for PN have not been adequately studied, and their evidence for use is based on small clinical trials, observational studies, and case reports.(2)

Topical therapies are the initial treatment for limited disease. Topical corticosteroids (TCS) target the immunologic component of PN.(2) The International Forum for the Study of Itch (IFSI) 2020 guideline on chronic prurigo including prurigo nodularis strongly recommends moderate to very potent topical corticosteroids on lesional skin.(3) Intralesional corticosteroids may be directly injected into thicker lesions where required, but use should be limited to patients with less than 10 lesions. Topical calcineurin inhibitors and topical calcipotriol have also been used in patients who failed TCS therapy and a prolonged course of a topical immunomodulator is desired. Topical capsaicin, which targets the neural component of PN, has limited clinical evidence and tends to have short term efficacy.(2)

Systemic therapies are used for widespread disease or disease refractory to topical therapy.(2,4) Phototherapy is reasonably tolerated and addresses both the immunologic and neural components of PN.(2) However, phototherapy combined with topical therapy will not be adequate for most patients, and the majority will require supplemental systemic therapy.(4) Oral immunosuppressants, such as methotrexate and cyclosporine, have shown to reduce pruritis and heal lesions per limited data available. Methotrexate is generally preferred due to its more favorable side effect profile in comparison to cyclosporine, and cyclosporine should only be considered in more severe cases.(2,4) Other systemic therapies that have shown to be less efficacious and treat the neural component of PN include thalidomide, gabapentin, pregabalin, antidepressants, aprepitant, and naltrexone.(2) Since PN is a nonhistaminergic condition, antihistamines are unlikely to be effective and are not recommended.(2,4)

Biologic agents are the first therapies to gain approval from the US Food and Drug Administration (FDA) for the treatment of PN. These immunomodulating drugs are believed to target molecules expressed by specific cell types that release a variety of itching mediators that directly or indirectly stimulate receptors on nerve endings in the skin. Biologic agents disrupt this cycle and have been proven to alleviate both pruritus and PN lesions.(4)

Efficacy

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). 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. 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. 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. The peak pruritus numeric rating scale (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.(1)

Subjects enrolled in these two trials had an IGA score greater than or equal to 3, severe pruritus as defined by a weekly average of the PP-NRS score of greater than or equal to 7 on a scale of 0 to 10, and greater than or equal to 20 nodular lesions. 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 baseline weekly average PP-NRS score was a mean of 8.5. Thirty-two (32)% of subjects had a history of atopy.(1) In the OLYMPIA 2 trial, 78.5% of subjects had previously used topical corticosteroids for the treatment of PN.(5) In both trials, patients were prohibited from using other therapies for PN such as topical corticosteroids, topical calcineurin inhibitors, or systemic immunomodulators, unless they were required as a rescue medication at the discretion of the investigator.(5,6)

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.(1)

Efficacy was assessed with the proportion of subjects with an improvement of greater than or equal to 4 from baseline in PP-NRS, the proportion of subjects with an IGA of 0 (Clear) or 1 (Almost Clear) and a greater than or equal to 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 less than 2.(1)

In both OLYMPIA 1 and OLYMPIA 2, statistically significant improvements in itch and PN skin lesions were observed at Week 16, with some subjects achieving this as early as Week 4. 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.(1,5,6)

Safety

Nemluvio is contraindicated in patients who have known hypersensitivity to nemolizumab-ilto or to any of the excipients of the product.(1)

1

Nemluvio prescribing information. Galderma Laboratories. August 2024.

2

Elmariah S, Kim B, Berger T, et al. Practical approaches for diagnosis and management of prurigo nodularis: United States expert panel consensus. J Am Acad Dermatol. 2021; 84:747-760.

3

Ständer S, Pereira MP, Berger TG, et al. IFSI-guideline on chronic prurigo including prurigo nodularis. Itch. 2020;5(4):e42. doi:10.1097/itx.0000000000000042

4

Yook HJ, Lee JH. Prurigo nodularis: Pathogenesis and the horizon of potential therapeutics. International Journal of Molecular Sciences. 2024;25(10):1-26. doi:10.3390/ijms25105164

5

Kwatra S, Yosipovitch G, Legat F, et al. Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis. New England Journal of Medicine. 2023;389(17):1579-1589. doi:10.1056/nejmoa2301333

6

Stander S, Yosipovitch G, Legat F, et al. Nemolizumab monotherapy improves itch and skin lesions in patients with moderate-to-severe prurigo nodularis: Results from a global phase 3 trial (OLYMPIA 1). European Academy of Dermatology and Venereology; 2023. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.eadv/abstracts_congress2023/39434.pdf

Nemluvio

nemolizumab-ilto for subcutaneous auto-injector

30 MG

M ; N ; O ; Y

N

Nemluvio

nemolizumab-ilto for subcutaneous auto-injector

30 MG

2

Pens

28

DAYS

calculation based on CDC 90 percentile for weight in adults and averaged for men and women to 247.5 lbs (112 kg)

9079355510D420

Nemluvio

nemolizumab-ilto for subcutaneous auto-injector

30 MG

calculation based on CDC 90 percentile for weight in adults and averaged for men and women to 247.5 lbs (112 kg)

Nemluvio

nemolizumab-ilto for subcutaneous auto-injector

30 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Nemluvio

nemolizumab-ilto for subcutaneous auto-injector

30 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PA

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. 1. 1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR 
      2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
   2. BOTH of the following:
      1. ONE of the following:
         1. The patient has a diagnosis of prurigo nodularis (PN) and ALL of the following:
            1. The patient has ALL of the following features associated with PN:
               1. Presence of greater than or equal to 20 firm, nodular lesions AND
               2. Pruritus that has lasted for at least 6 weeks AND
               3. History and/or signs of repeated scratching, picking, or rubbing AND
            2. ONE of the following:
               1. The patient has tried and had an inadequate response to at least a medium-potency topical corticosteroid used in the treatment of PN after at least a 2-week duration of therapy OR
               2. The patient has an intolerance or hypersensitivity to therapy with at least a medium-potency topical corticosteroid used in the treatment of PN OR
               3. The patient has an FDA labeled contraindication to ALL medium-, high-, and super-potency topical corticosteroids used in the treatment of PN AND
            3. ONE of the following:
               1. The patient has tried and had an inadequate response to Dupixent for the treatment of PN after at least a 3-month duration of therapy OR
               2. The patient has an intolerance (defined as an intolerance to the drug or its excipients, not to the route of administration) or hypersensitivity to Dupixent OR
               3. The patient has an FDA labeled contraindication to Dupixent OR
         2. The patient has another FDA labeled indication for the requested agent and route of administration AND
      2. If the patient has an FDA labeled indication, then ONE of the following:
         1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
         2. There is support for using the requested agent for the patient’s age for the requested indication OR
   3. The patient has another indication that is supported in compendia for the requested agent and route of administration AND
2. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., allergist, dermatologist, immunologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
3. ONE of the following (please refer to “Agents NOT to be used Concomitantly” table): 
   1. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR
   2. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following:
      1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND
      2. There is support for the use of combination therapy (submitted copy of clinical trials, phase III studies, or guidelines required) AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS, DrugDex 1 or 2a level of evidence, or NCCN 1 or 2a recommended use

Length of Approval: 4 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., allergist, dermatologist, immunologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. ONE of the following (please refer to “Agents NOT to be used Concomitantly” table): 
   1. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR
   2. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following:
      1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND
      2. There is support for use of combination therapy (submitted copy of clinical trials, phase III studies, or guidelines required) AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS, DrugDex 1 or 2a level of evidence, or NCCN 1 or 2a recommended use

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR  
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit

Length of Approval: up to 12 months

Agents NOT to be used Concomitantly

Abrilada (adalimumab-afzb)
Actemra (tocilizumab)
Adalimumab
Adbry (tralokinumab-ldrm)
Amjevita (adalimumab-atto)
Arcalyst (rilonacept)
Avsola (infliximab-axxq)
Benlysta (belimumab)
Bimzelx (bimekizumab-bkzx)
Cibinqo (abrocitinib)
Cimzia (certolizumab)
Cinqair (reslizumab)
Cosentyx (secukinumab)
Cyltezo (adalimumab-adbm)
Dupixent (dupilumab)
Ebglyss (lebrikizumab-lbkz)
Enbrel (etanercept)
Entyvio (vedolizumab)
Fasenra (benralizumab)
Hadlima (adalimumab-bwwd)
Hulio (adalimumab-fkjp)
Humira (adalimumab)
Hyrimoz (adalimumab-adaz)
Idacio (adalimumab-aacf)
Ilaris (canakinumab)
Ilumya (tildrakizumab-asmn)
Imuldosa (ustekinumab-srlf)
Inflectra (infliximab-dyyb)
Infliximab
Kevzara (sarilumab)
Kineret (anakinra)
Leqselvi (deuruxolitinib)
Litfulo (ritlecitinib)
Nemluvio (nemolizumab-ilto)
Nucala (mepolizumab)
Olumiant (baricitinib)
Omvoh (mirikizumab-mrkz)
Opzelura (ruxolitinib)
Orencia (abatacept)
Otezla (apremilast)
Otulfi (ustekinumab-aauz)
Pyzchiva (ustekinumab-ttwe)
Remicade (infliximab)
Renflexis (infliximab-abda)
Riabni (rituximab-arrx)
Rinvoq (upadacitinib)
Rituxan (rituximab)
Rituxan Hycela (rituximab/hyaluronidase human)
Ruxience (rituximab-pvvr)
Saphnelo (anifrolumab-fnia)
Selarsdi (ustekinumab-aekn)
Siliq (brodalumab)
Simlandi (adalimumab-ryvk)
Simponi (golimumab)
Simponi ARIA (golimumab)
Skyrizi (risankizumab-rzaa)
Sotyktu (deucravacitinib) 
Spevigo (spesolimab-sbzo) subcutaneous injection
Stelara (ustekinumab)
Taltz (ixekizumab)
Tezspire (tezepelumab-ekko)
Tofidence (tocilizumab-bavi)
Tremfya (guselkumab)
Truxima (rituximab-abbs)
Tyenne (tocilizumab-aazg)
Tysabri (natalizumab)
Velsipity (etrasimod)
Wezlana (ustekinumab-auub)
Xeljanz (tofacitinib)
Xeljanz XR (tofacitinib extended release)
Xolair (omalizumab)
Yuflyma (adalimumab-aaty)
Yusimry (adalimumab-aqvh)
Zeposia (ozanimod)
Zymfentra (infliximab-dyyb)