Depemokimab-ulaa (Exdensur)

Number: 1098

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Brand Selection for Medically Necessary Indications for Commercial Medical Plans

According to Aetna commercial benefit plans, health care services are considered not medically necessary if they are more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that member’s illness, injury or disease. Aetna commercial plans may require a trial of a lower-cost drug (preferred medication) that is at least as likely to produce equivalent therapeutic results before approving coverage for a higher-cost drug within the same therapeutic class. For a list of preferred drugs, refer to the Aetna Commercial Clinical Program Summary.

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses depemokimab-ulaa (Exdensur) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of depemokimab-ulaa (Exdensur) is required of all Aetna participating providers and members in applicable plan designs. For precertification of depemokimab-ulaa, call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification.

Note: Site of Care Utilization Management Policy applies for commercial plans. For information on site of service for depemokimab-ulaa (Exdensur), see Utilization Management Policy on Site of Care for Specialty Drug Infusions.

1. Prescriber Specialties

   This medication must be prescribed by or in consultation with an allergist/immunologist or pulmonologist.

2. Criteria for Initial Approval

   Aetna considers depemokimab-ulaa (Exdensur) medically necessary for the treatment of asthma when criteria are met:

   1. For members 12 years of age or older who have previously received a biologic drug (e.g., Dupixent, Nucala) indicated for asthma in the past 12 months. Member will continue to use maintenance asthma treatments (e.g., inhaled corticosteroid [ICS] and additional controller) in combination with the requested medication; or
   2. For treatment of severe asthma when all of the following criteria are met:
      
      
      1. Member is 12 years of age or older; and
      2. Member meets either of the following:
         
         
         1. Member has a baseline blood eosinophil count of at least 150 cells per microliter; or
         2. Member is dependent on oral systemic corticosteroids; and

      3. Member has uncontrolled asthma as demonstrated by experiencing at least one of the following within the past 12 months:

         1. Two or more asthma exacerbations requiring oral or injectable corticosteroid treatment; or
         2. One or more asthma exacerbation(s) resulting in hospitalization or emergency medical care visit(s); or
         3. Poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma); and

      4. Member has inadequate asthma control despite current treatment with both of the following medications at optimized doses:

         1. High-dose ICS (see Appendix); and
         2. Additional controller (i.e., long acting beta₂-agonist [LABA], long acting muscarinic antagonist [LAMA], leukotriene modifier, or sustained-release theophylline); and

      5. Member will continue to use maintenance asthma treatments (e.g., ICS and additional controller) in combination with the requested medication.

            Aetna considers all other indications as experimental, investigational, or unproven.

3. Continuation of Therapy

   Aetna considers continuation of depemokimab-ulaa (Exdensur) therapy medically necessary for treatment of severe asthma when all of the following criteria are met:

   1. Member is 12 years of age or older; and
   2. Asthma control has improved on the requested medication as demonstrated by at least one of the following:
      
      
      1. A reduction in the frequency and/or severity of symptoms and exacerbations; or
      2. A reduction or discontinuation in the daily maintenance oral corticosteroid dose; and
         

   3. Member will continue to use maintenance asthma treatments (e.g., ICS and additional controller) in combination with the requested medication.

4. Other

   Member cannot use the requested medication concomitantly with any other biologic drug or targeted synthetic drug for the same indication.

   Note: If the member is a current smoker or vaper, they should be counseled on the harmful effects of smoking and vaping on pulmonary conditions and available smoking and vaping cessation options.

5. Related Policies 

   1. CPB 0670 - Omalizumab
   2. CPB 0897 - Mepolizumab (Nucala)
   3. CPB 0907 - Reslizumab (Cinqair)
   4. CPB 0925 - Benralizumab (Fasenra)
   5. CPB 1003 - Tezepelumab-ekko (Tezspire).

Dosage and Administration

Depemokimab-ulaa is available as Exdensur and supplied for subcutaneous (SC) injection in the following dosage forms and strengths:

• 100 mg/mL solution in a single-dose prefilled pen
• 100 mg/mL solution in a single-dose prefilled syringe

The recommended dosage is 100 mg injected subcutaneously once every 6 months. Exdensur should be administered by a healthcare provider.

Source: GlaxoSmithKline, 2025a

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
96372	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
96401	Chemotherapy administration, subcutaneous or intramuscular; non-hormonal anti-neoplastic
99406	Smoking and tobacco use cessation counseling visit; intermediate, greater than 3 minutes up to 10 minutes
99407	intensive, greater than 10 minutes
HCPCS codes covered if selection criteria are met:
J2361	Injection, depemokimab-ulaa, 1 mg
Other HCPCS codes related to the CPB:
Dupixent, Ciclesonide, Fluticasone furoate, Fluticasone propionate, Mometasone furoate, leukotriene modifier, or sustained-release theophylline)- No specific code
J0702	Injection, betamethasone acetate 3 mg and betamethasone sodium phosphate 3 mg
J1010	Injection, methylprednisolone acetate, 1 m
J1100	Injection, dexamethasone sodium phosphate, 1 m
J1700	Injection, hydrocortisone acetate, up to 25 mg
J1720	Injection, hydrocortisone sodium succinate, up to 100 mg
J2182	Injection, mepolizumab, 1 mg
J2650	Injection, prednisolone acetate, up to 1 ml
J2810	Injection, theophylline, per 40 mg
J2919	Injection, methylprednisolone sodium succinate, 5 mg
J3299-J3304	Injection, triamcinolone
J7402	Mometasone furoate sinus implant, (Sinuva), 10 mcg
J7509	Methylprednisolone oral, per 4 mg
J7510	Prednisolone oral, per 5 mg
J7512	Prednisone, immediate release or delayed release, oral, 1 m
J7605	Arformoterol, inhalation solution, fda approved final product, non-compounded, administered through dme, unit dose form, 15 micrograms
J7606	Formoterol fumarate, inhalation solution, fda approved final product, non-compounded, administered through dme, unit dose form, 20 micrograms
J7607	Levalbuterol, inhalation solution, compounded product, administered through dme, concentrated form, 0.5 mg
J7612	Levalbuterol, inhalation solution, fda-approved final product, non-compounded, administered through dme, concentrated form, 0.5 mg
J7614	Levalbuterol, inhalation solution, fda-approved final product, non-compounded, administered through dme, unit dose, 0.5 mg
J7615	Levalbuterol, inhalation solution, compounded product, administered through dme, unit dose, 0.5 mg
J7620	Albuterol, up to 2.5 mg and ipratropium bromide, up to 0.5 mg, fda-approved final product, non-compounded, administered through dme
J7622	Beclomethasone, inhalation solution, compounded product, administered through dme, unit dose form, per milligram
J7626	Budesonide, inhalation solution, fda-approved final product, non-compounded, administered through dme, unit dose form, up to 0.5 mg
J7627	Budesonide, inhalation solution, compounded product, administered through dme, unit dose form, up to 0.5 mg
J7631-J7632	Cromolyn sodium, inhalation solution
J7633	Budesonide, inhalation solution, fda-approved final product, non-compounded, administered through dme, concentrated form, per 0.25 milligram
J7634	Budesonide, inhalation solution, compounded product, administered through dme, concentrated form, per 0.25 milligram
J7637-J7638	Dexamethasone, inhalation solution
J7640	Formoterol, inhalation solution, compounded product, administered through dme, unit dose form, 12 micrograms
J7641	Flunisolide, inhalation solution, compounded product, administered through dme, unit dose, per milligram
J7644	Ipratropium bromide, inhalation solution, fda-approved final product, non-compounded, administered through dme, unit dose form, per milligram
J7645	Ipratropium bromide, inhalation solution, compounded product, administered through dme, unit dose form, per milligram
J7657-J7660	Isoproterenol hcl, inhalation solution
J7667-J7670	Metaproterenol sulfate, inhalation solution
J7677	Revefenacin inhalation solution, fda-approved final product, non-compounded, administered through DME, 1 microgram
J7683-J7684	Triamcinolone, inhalation solution
J8540	Dexamethasone, oral, 0.25 mg
J8541	Dexamethasone (hemady), oral, 0.25 mg
ICD-10 codes covered if selection criteria are met:
J45.20	Mild intermittent asthma, uncomplicated
J45.21	Mild intermittent asthma with (acute) exacerbation
J45.30	Mild persistent asthma, uncomplicated
J45.31	Mild persistent asthma with (acute) exacerbation
J45.40	Moderate persistent asthma, uncomplicated
J45.41	Moderate persistent asthma with (acute) exacerbation
J45.50	Severe persistent asthma, uncomplicated
J45.51	Severe persistent asthma with (acute) exacerbation
J45.901	Unspecified asthma with (acute) exacerbation

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications

• Exdensur is indicated for the add-on maintenance treatment of severe asthma characterized by an eosinophilic phenotype in adult and pediatric patients aged 12 years and older.

  Limitations of Use:

• • Not for the relief of acute bronchospasm or status asthmaticus.

Depemokimab-ulaa, branded as Exdensur (GlaxoSmithKline), is a IL-5 antagonist (humanized IgG1 kappa monoclonal antibody). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Although the exact mechanism of action of depemokimab-ulaa in asthma not established, by inhibit IL-5-signaling, depemokimab-ulaa reduced the production and survival of eosinophils. Depemokimab-ulaa contains a triple amino acid substitution (YTE) which increases binding to the neonatal Fc receptor and thereby extends the elimination half-life, allowing a long dosing interval of every 6 months.

Exdensur carries labeled warnings and precautions for hypersensitivity reactions, including anaphylaxis, and parasitic (helminth) infection. The Prescribing Information (PI) advises patients to not abruptly discontinue systemic or inhaled corticosteroids upon initiation of Exdensur therapy. Reductions in corticosteroid dosage, if appropriate, should be gradual and performed under the direct supervision of a healthcare provider. Reduction in corticosteroid dosage may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy. Per the PI, eosinophils may be involved in the immunological response to some helminth infections. Patients with pre-existing parasitic infections were excluded from participation in clinical trials. Thus, it is unknown if Exdensur will influence a patient’s response against parasitic infections. Healthcare providers are advised to treat patients with pre-existing helminth infections before initiating therapy with Exdensur. If patients become infected while receiving treatment with Exdensur and do not respond to anti-helminth treatment, Exdensur should be discontinued until infection resolves.

The most common adverse reactions (incidence greater than or equal to 4%) include upper respiratory tract infection, allergic rhinitis, influenza, arthralgia, and pharyngitis. 

Asthma

Asthma is chronic, heterogenous condition that is usually characterized by chronic airway inflammation and associated with airway hyperresponsiveness.  Asthma is defined by the history of respiratory symptoms, such as wheeze, shortness of breath, chest tightness and cough, that vary over time and in intensity, together with variable expiratory airflow. Airflow limitation may later become persistent (GINA, 2025).

According to the Global Initiative for Asthma (GINA) (2025), severe asthma is defined as asthma that is uncontrolled despite optimized treatment with high-dose inhaled corticosteroid (ICS)-long-acting beta₂ agonist (LABA), or that requires high dose ICS-LABA or biologic therapy to remain controlled. Severe asthma impacts an estimated 2 million people in the United States and 50% of patients continue to frequent exacerbations that results in emergency department visit and hospitalizations. (GINA, 2025; GlaxoSmithKline, 2025b)

Eosinophilic asthma is an asthma subtype that accounts for about 70% of all cases of severe asthma. Tissue and sputum eosinophilia, basement membrane thickening, and often response to corticosteroids are characteristics of eosinophilic asthma, as well as peripheral blood eosinophilic counts of at least 150 cells per microliter. Asthma with elevated blood eosinophil count also support the diagnosis of Type 2 asthma (Porpodis, et al., 2022; GINA, 2025).

The GINA guidelines states to consider add-on targeted biologic therapy for patients with exacerbations or poor symptom control on high dose ICS-LABA who have evidence of Type 2 inflammation, characterized by elevated eosinophils or increased fractional exhaled nitric oxide, and it may be accompanied by atopy and elevated IgE. The guidelines recommend an add-on Type 2 targeted biologic for patients with exacerbations and/or poor symptom control despite taking at least high-dose ICS-LABA, and who have allergic or eosinophilic biomarkers or need maintenance oral corticosteroids. 

Maintenance treatment includes medications to be used continuously, even when the person does not have asthma symptoms. Examples include ICS-containing medications (ICS, ICS-LABA, ICS-LABA-LAMA), as well as LTRA (leukotriene receptor antagonist) and biologic therapy. Treatment regimen in which the patient uses an ICS-formoterol inhaler every day (maintenance dose) and also uses the same medication as needed for relief of asthma symptoms (reliever doses), is referred to as maintenance-and-reliever therapy (MART). The GINA guidelines noted that if asthma is confirmed well controlled after initiation of biologic therapy for a minimum of 3 to 6 months, discontinuation or dose reduction of inhaled maintenance treatments can be considered,  The guidance emphasized add-on inhaled agents such as LAMA should be ceased prior to dose tapering ICS-LABA dose and that ICS-containing therapy should not ceased completely (GINA, 2025).

On December 16, 2025, the FDA announced the approval of Exdensur (depemokimab-ulaa) as an add-on maintenance treatment of severe asthma characterized by an eosinophilic type in adult and pediatric patients aged 12 years and older. Approval was based on results obtained from phase 3 clinical trials SWIFT-1 and SWIFT-2 (GlaxoSmithKline, 2025b).

The SWIFT-1 and SWIFT-2 studies were randomized, placebo-controlled, phase 3A trials which included severe asthmatic patients 12 years of age or older, with an eosinophilic phenotype (blood eosinophil count greater than or equal to 300 cells per microliter in the past year or greater than or equal to 150 cells per microliter). Participants were required to have a diagnosis of asthma for at least 2 years with airflow obstruction, receiving medium- or high-dose inhaled corticosteroids in the past year and an additional controller for at least 3 months. Furthermore, subjects are required to have taken systemic glucocorticoids due to experiencing at least two asthma exacerbations in the past year. Patients who received biologic therapy or anti-leukin-5 antibody in the past year were excluded. The primary endpoint is the annualized rate of exacerbations within 52 weeks. Change in total score of the St. George's respiratory Questionnaire (SGRQ) from baseline, change in score on the Asthma Control Questionaire-5, prebronchodilator forced expiratory volume in 1 second (FEV1), scores on asthma nightly and daily symptom diaries, and annualized rate of exacerbations resulted in hospitalization or emergency department visit within 52 weeks are secondary end points. The minimal clinically important difference (MCID) of St. George's respiratory Questionnaire from baseline, change in score on the Asthma Control Questionaire-5, and scores on asthma nightly and daily symptom diaries are -4.0, -0.5,-1.5 (nightly score), and -1.2 (daily score) respectively. A total of 762 patients were included, with similar demographics and patient characteristics, and 90% of patients had blood eosinophil count of greater than or equal to 150 cells per microliter. At 52 weeks, the depemokimab groups in both SWIFT-1 and SWIFT-2 trials demonstrated significantly lower annualized rate of exacerbations than placebo (0.46 vs 1.11, p < 0.001; 0.56 vs 1.08, p < 0.001, respectively). The annualized rate of exacerbations of depemokimab in the pool analysis was 0.51 (95% CI, 0.43 to 0.60) versus 1.1 (95% CI, 0.92 to 1.33) with placebo, for a rate ratio of 0.46 (95% CI, 0.36 to 0.59). The change in the SGRQ score from baseline was not statistically significant in both trials (p = 0.08 and p = 0.20 respectively); thus, no statistical inference was drawn on subsequent secondary end points. The frequency of adverse events in depemokimab group was similar to placebo in both trials. The investigators noted enrolling only patients with severe asthma but without previously tried biologic therapy was a challenge and limits the applicability of the results to patients in this population. Furthermore, adherence to standard care was not monitored and the study was conducted during the coronavirus disease 2019 pandemic are other limitations of the study. Despite the constraints, the authors concluded depemokimab, administered every 6 months reduced the annualized rate of exacerbations in patients with severe asthma with an eosinophilic phenotype (Jackson et al., 2024).

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Appendix

Examples of high-dose ICS (alone or in combination with LABA) for adults and adolescents (12 years and older)

Drug	Dosage Form	Total Daily Dose
Beclomethasone dipropionate	Pressurized metered-dose inhaler (pMDI), standard particle size hydrofluoroalkane propellant (HFA)	> 1000 mcg
Beclomethasone dipropionate	Dry-powder inhaler (DPI) or pMDI, extra-fine particle size HFA	> 400 mcg
Budesonide	DPI or pMDI, standard particle size HFA	> 800 mcg
Ciclesonide	pMDI, extra-fine particle size HFA	> 320 mcg
Fluticasone furoate	DPI	200 mcg
Fluticasone propionate	DPI or pMDI, standard particle size HFA	> 500 mcg
Mometasone furoate	DPI or pMDI, standard particle size HFA	> 400 mcg

Source: Global Initiative for Asthma (GINA), 2025

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References