Tezepelumab-ekko (Tezspire)

Number: 1003

Table Of Contents

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

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses tezepelumab-ekko (Tezspire) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification:

Precertification of tezepelumab-ekko (Tezspire) is required of all Aetna participating providers and members in applicable plan designs. For precertification of tezepelumab-ekko (Tezspire), 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 information on site of service for tezepelumab-ekko (Tezspire), 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 tezepelumab-ekko (Tezspire) medically necessary for treatment of severe 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; 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 has uncontrolled asthma as demonstrated by experiencing at least one of the following within the past year:
         
         
         1. Two or more asthma exacerbations requiring oral or injectable corticosteroid treatment; or
         2. One or more asthma exacerbation resulting in hospitalization or emergency medical care visit; or
         3. Poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma); and

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

         1. High dose inhaled corticosteroid; and
         2. Additional controller (i.e., long acting beta₂-agonist, long acting muscarinic antagonists, leukotriene modifier, or sustained-release theophylline); and
            

      4. Member will continue to use maintenance asthma treatments (e.g., inhaled corticosteroid, additional controller) in combination with the requested medication.

   Aetna considers all other indications as experimental and investigational.

3. Continuation of Therapy

   Aetna considers continuation of tezepelumab-ekko (Tezspire) therapy medically necessary for the 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 in the daily maintenance oral corticosteroid dose; and
         

   3. Member will continue to use maintenance asthma treatments (e.g., inhaled corticosteroid, additional controller) in combination with Tezspirethe 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 0059 - Peak Flow Meters
   2. CPB 0670 - Omalizumab (Xolair)
   3. CPB 0897 - Mepolizumab (Nucala)
   4. CPB 0907 - Reslizumab (Cinqair)
   5. CPB 0925 - Benralizumab (Fasenra)

Dosage and Administration

Tezspire is supplied for injection as 210 mg of tezepelumab-ekko in 1.91 mL (110 mg/mL) solution in a single-dose glass vial, pre-filled syringe, and a pre-filled pen. 

The recommended dosage of Tezspire is 210 mg once every 4 weeks administered subcutaneously.  Tezspire vial and pre-filled syringe are intended for administration by a healthcare
provider. The pre-filled pen can be self-administered or administered by caregivers or healthcare providers.

Source: Amgen, 2023

Experimental and Investigational

Aetna considers tezepelumab experimental and investigational for the following indications (not an all-inclusive list) because the safety and/or effectiveness for these indications has not been established:

1. Allergic broncho-pulmonary aspergillosis
2. Chronic rhinosinusitis with nasal polyps
3. Combined tezepelumab and allergen immunotherapy for the treatment of allergic rhinitis.

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
95115 - 95199	Allergen immunotherapy
96401	Chemotherapy administration, subcutaneous or intramuscular; non-hormonal anti-neoplastic
96372	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
HCPCS codes covered if selection criteria are met:
J2356	Injection, tezepelumab-ekko, 1 mg
Other HCPCS codes related to the CPB:
J0517	Injection, benralizumab, 1 mg
J0702	Injection, betamethasone acetate 3 mg and betamethasone sodium phosphate 3 mg
J1020	Injection, methylprednisolone acetate, 20 mg
J1030	Injection, methylprednisolone acetate, 40 mg
J1040	Injection, methylprednisolone acetate, 80 mg
J1094	Injection, dexamethasone acetate, 1 mg
J1100	Injection, dexamethasone sodium phosphate, 1 mg
J1700	Injection, hydrocortisone acetate, up to 25 mg
J1710	Injection, hydrocortisone sodium phosphate, up to 50 mg
J1720	Injection, hydrocortisone sodium succinate, up to 100 mg
J2182	Injection, mepolizumab, 1 mg
J2357	Injection, omalizumab, 5 mg
J2650	Injection, prednisolone acetate, up to 1 ml
J2786	Injection, reslizumab, 1 mg
J2810	Injection, theophylline, per 40 mg
J2920	Injection, methylprednisolone sodium succinate, up to 40 mg
J2930	Injection, methylprednisolone sodium succinate, up to 125 mg
J7509	Methylprednisolone oral, per 4 mg
J7510	Prednisolone oral, per 5 mg
J7512	Prednisone, immediate release or delayed release, oral, 1 mg
J7606	Formoterol fumarate, inhalation solution, fda approved final product, non-compounded, administered through dme, unit dose form, 20 micrograms
J7609	Albuterol, inhalation solution, compounded product, administered through dme, unit dose, 1 mg
J7610	Albuterol, inhalation solution, compounded product, administered through dme, concentrated form, 1 mg
J7611	Albuterol, inhalation solution, fda-approved final product, non-compounded, administered through dme, concentrated form, 1 mg
J7613	Albuterol, inhalation solution, fda-approved final product, non-compounded, administered through dme, unit dose, 1 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
J7640	Formoterol, inhalation solution, compounded product, administered through dme, unit dose form, 12 micrograms
J8540	Dexamethasone, oral, 0.25 mg
ICD-10 codes covered if selection criteria are met:
J45.50 - J45.52	Severe persistent asthma
ICD-10 codes not covered for indications listed in the CPB:
B44.81	Allergic bronchopulmonary aspergillosis
J30.1 – J30.9	Allergic rhinitis
J32.0 – J32.9	Chronic sinusitis
J33.0 – J33.9	Nasal polyp

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Background

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

• Tezspire is indicated for add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.

  Limitations of use: Not for relief of acute bronchospasm or status asthmaticus.

Tezepelumab-ekko is available as Tezspire (Amgen Inc.). Tezepelumab-ekko is a thymic stromal lymphopoietin (TSLP) blocker, human monoclonal antibody (IgG2λ). TSLP, a molecule involved in airway inflammation, is a cytokine mainly derived from epithelial cells and occupies an upstream position in the asthma inflammatory cascade. Airway inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes, ILC2 cells) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in airway inflammation. Blocking TSLP with tezepelumab-ekko reduces biomarkers and cytokines associated with inflammation including blood eosinophils, airway submucosal eosinophils, IgE, FeNO, IL-5, and IL-13; however, the mechanism of tezepelumab-ekko action in asthma has not been definitively established (Amgen, 2023).

Tezspire carries labeled warnings and precautions for hypersensitivity reactions (e.g., rash and allergic conjunctivitis) and risk for parasitic (helminth) infection. Hypersensitivity reactions can occur within hours of administration, but in some instances have a delayed onset (i.e., days). TSLP may be involved in the immunological response to some helminth infections; however, patients with known helminth infections were excluded from participation in clinical trials. Thus, it is unknown if Tezspire will influence a patient’s response against helminth infections. 

Per the label, Tezspire should not be used to treat acute asthma symptoms or acute exacerbations. Tezspire is not to be used to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with Tezspire. It is recommended that patients do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with Tezspire. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy. 

The concomitant use of Tezspire and live attenuated vaccines has not been evaluated. Therefore, the use of live attenuated vaccines should be avoided in patients receiving Tezspire.

The most common adverse reactions (incidence of 3% or more) include pharyngitis, arthralgia, and back pain. 

Asthma

Asthma is chronic, heterogenous condition that is usually associated with airway inflammation and bronchial hyperresponsiveness which results in narrowing of the airways, leading to less airflow to the lungs. Airway swelling or inflammation can be triggered by several factors, including allergens or irritant exposure and viral infections. Respiratory symptoms, "asthma attack" exacerbation, may include wheeze, chest tightness, shortness of breath, and/or cough, which can vary in frequency and intensity over time. Airflow limitation may later become persistent and severe (GINA, 2021; FDA, 2021).

According to the Global Initiative for Asthma (GINA) (2021), severe asthma is defined as asthma that is uncontrolled despite high dose inhaled corticosteroid (ICS)-long-acting beta₂ agonist (LABA), or that requires high dose ICS-LABA to remain controlled. "Severe asthma attacks can be intense, last for long periods of time, and impact daily activities. Severe asthma symptoms usually do not get better with use of short-term treatments. Approximately 5-10 percent of Americans with asthma have severe asthma" (FDA, 2021).

On December 20, 2021, the FDA announced the approval of the first asthma treatment targeting thymic stromal lymphopoietin (TSLP). Tezspire (tezepelumab-ekko), a TSLP blocker, human monoclonal antibody (IgG2λ), was approved as an add-on maintenance treatment used to improve severe asthma symptoms when used with a patient’s current asthma medicine. Tezspire is approved for adults and children aged 12 years and older with severe asthma not controlled by their current asthma medicine. Tezspire is also the first treatment for severe asthma that is not limited to a specific type of severe asthma. Tezspire is administered once every four weeks as a subcutaneous injection by a health care professional.

FDA approval as based on the safety and efficacy in two randomized, double-blind, parallel group, placebo-controlled clinical trials (PATHFINDER, NCT02054130; NAVIGATOR, NCT03347279) in which patients receiving Tezspire had significant reductions in the annualized rate of asthma attacks compared to placebo. Additionally, there were fewer asthma attacks requiring emergency room visits and/or hospitalization among patients treated with Tezspire compared to placebo. The benefits of Tezspire seen in patients weren’t limited by specific severe asthma type (FDA, 2021).

Corren et al (2021) state that in the phase 2b PATHWAY study, tezepelumab reduced exacerbations by up to 71% and improved lung function, asthma control, and health-related quality of life vs placebo. Adults with severe, uncontrolled asthma were randomized to subcutaneous tezepelumab (70 mg every 4 weeks, 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. Inclusion criteria required documented physician-diagnosed asthma. Patients must have received a physician-prescribed asthma controller regimen with medium- or high-dose inhaled corticosteroids (ICS) plus long acting β2 agonist (LABA). If on asthma controller medications in addition to ICS plus LABA, the dose of the other asthma controller medications (leukotriene receptor inhibitors, theophylline, secondary ICS, long-acting anti-muscarinics (LAMA), cromones, or maintenance oral prednisone or equivalent up to a maximum of 10 mg daily or 20 mg every other day for the maintenance treatment of asthma) must be stable. Patients must have a documented history of at least 2 asthma exacerbation events or at least 1 severe asthma exacerbation resulting in hospitalization within the 12 months prior to first study visit. Patient-reported outcomes (PROs) were assessed using the asthma control questionnaire-6 (ACQ-6) and the asthma quality of life questionnaire (standardized) for patients aged 12 years or older (AQLQ[S]+12). The proportions of responders (defined by improvements of ≥0.5 in ACQ-6 or AQLQ(S)+12 scores) and patients whose asthma was well-controlled, partially-controlled, or uncontrolled in the tezepelumab and placebo groups were identified. The Asthma Daily Diary questionnaire was used to assess changes in overall symptom severity. Overall, 550 patients were randomized. The authors found that up to 82% and 77% of tezepelumab-treated patients were ACQ-6 and AQLQ(S)+12 responders, respectively, compared with 70% and 64% of placebo-treated patients, respectively. The proportions of patients with well-controlled or partially-controlled asthma were higher in the tezepelumab-treated group than in the placebo group. In addition, tezepelumab improved the overall symptom severity. The authors concluded that tezepelumab treatment improved PROs vs placebo, as indicated by the higher proportion of ACQ-6 and AQLQ(S)+12 responders and improvements in symptom severity in the tezepelumab dose groups. These data further support the benefits of tezepelumab in patients with severe, uncontrolled asthma.

Menzies-Gow et al (2021) conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial (NAVIGATOR). Patients (12 to 80 years of age; n=1061) were randomly assigned to receive tezepelumab (210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. Inclusion criteria required patients, aged 12 to 80 years, to have documented physician-diagnosed asthma for at least 12 months, have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 12 months, documented treatment with a total daily dose of either medium or high dose ICS (≥ 500 µg fluticasone propionate dry powder formulation equivalent total daily dose) for at least 3 months, have at least one additional maintenance asthma controller medication according to standard practice of care for at least 3 months, morning pre-BD FEV1 <80% predicted normal (<90% for subjects 12-17 years), evidence of asthma as documented by either: documented historical reversibility of FEV1 ≥12% and ≥200 mL in the previous 12 months or post-BD (albuterol/salbutamol) reversibility of FEV1 ≥12% and ≥200 mL during screening, documented history of at least 2 asthma exacerbation events within 12 months, and have an ACQ-6 score ≥1.5 at screening and on day of randomization. The primary end point was the annualized rate of asthma exacerbations over a period of 52 weeks. This end point was also assessed in patients with baseline blood eosinophil counts of less than 300 cells per microliter. Secondary end points included the forced expiratory volume in 1 second (FEV1) and scores on the Asthma Control Questionnaire-6 (ACQ-6; range, 0 [no impairment] to 6 [maximum impairment]), Asthma Quality of Life Questionnaire (AQLQ; range, 1 [maximum impairment] to 7 [no impairment]), and Asthma Symptom Diary (ASD; range, 0 [no symptoms] to 4 [worst possible symptoms]). Overall, 1061 patients underwent randomization (529 were assigned to receive tezepelumab and 532 to receive placebo). The annualized rate of asthma exacerbations was 0.93 (95% confidence interval [CI], 0.80 to 1.07) with tezepelumab and 2.10 (95% CI, 1.84 to 2.39) with placebo (rate ratio, 0.44; 95% CI, 0.37 to 0.53; p<0.001). In patients with a blood eosinophil count of less than 300 cells per microliter, the annualized rate was 1.02 (95% CI, 0.84 to 1.23) with tezepelumab and 1.73 (95% CI, 1.46 to 2.05) with placebo (p<0.001). At week 52, improvements were greater with tezepelumab than with placebo with respect to the prebronchodilator FEV1 (p<0.001) and scores on the ACQ-6 (p<0.001), AQLQ (p<0.001), and ASD (p = 0.002). The frequencies and types of adverse events did not differ meaningfully between the two groups. The authors concluded that patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo. 

Allergic Broncho-Pulmonary Aspergillosis

Ogata et al (2023) reported on the case of an 82-year-old man who had been diagnosed with asthma.  He experienced repeated exacerbations requiring treatment with a systemic corticosteroid despite being treated with medications including high-dose fluticasone furoate/umeclidinium/vilanterol, montelukast sodium, and theophylline; treatment with mepolizumab was then initiated.  The patient had been free from exacerbations for 15 months; however, he suffered from post-obstructive pneumonia and atelectasis secondary to mucoid impaction in the right middle lobe of the lung, accompanied by a productive cough, wheezing, dyspnea, and right chest pain . In addition to the development of mucus plugs, the levels of serum IgE specific to Aspergillus spp. became positive; a definite diagnosis of allergic broncho-pulmonary aspergillosis (ABPA) was established.  The patient underwent treatment with tezepelumab.  Over 3 months, the mucus plugs and pulmonary opacities diminished gradually in parallel with the improvement in the control of asthmatic symptoms.  The authors concluded that tezepelumab might provide a novel steroid-sparing strategy for the management of ABPA, although further studies are needed to validate these findings.

Chronic Rhinosinusitis with Nasal Polyps

Chiang and Lee (2023) stated that epithelial barrier disturbances in patients with chronic rhinosinusitis with nasal polyps play an important role in both the innate and adaptive immune responses, contributing to chronic inflammation, olfactory dysfunction, and impairments in quality of life (QOL).  These researchers examined the role of the sinonasal epithelium in disease and health, reviewed the pathophysiology of epithelial barrier dysfunction in CRSwNP, and the immunologic targets for treatment.  Blockade of cytokines such as thymic stromal lymphopoietin (TSLP), IL-4, and IL-13 have shown promise in barrier restoration and IL-13, specifically may be central to olfactory dysfunction.  The authors concluded that the sinonasal epithelium plays a crucial role in the health and function of the mucosa and immune response.  Increased understanding of the local immunologic dysfunction has led to several therapeutics that can potentially restore epithelial barrier function and olfaction.  Real world and comparative effectiveness studies are needed.  Tezepelumab is one of the key words in this literature review.

Combined Tezepelumab and Allergen Immunotherapy for the Treatment of Allergic Rhinits

Corren et al (2023) stated that TSLP has been shown to play a central role in the initiation and persistence of allergic responses.  In a double-blind, parallel design study, these researchers examined if Tezepelumab would improve the effectiveness of subcutaneous allergen immunotherapy (SCIT) and promote the development of tolerance in patients with allergic rhinitis.  A total of 121 patients were randomized to receive either intravenous tezepelumab plus subcutaneous cat SCIT, cat SCIT alone, tezepelumab alone, or placebo for 52 weeks, followed by 52 weeks of observation.  Nasal allergen challenge (NAC), skin testing, and blood and nasal samples were obtained throughout the study.  At week 52, the NAC-induced total nasal symptom scores (TNSS) (calculated as area under the curve [AUC0-1h] and as peak score [Peak0-1h] during the 1st hour following NAC) were significantly reduced in patients receiving tezepelumab/SCIT compared to SCIT alone.  At week 104, 1 year after stopping treatment, the primary endpoint TNSS AUC0-1h was not significantly different in the tezepelumab/SCIT group compared to SCIT alone, while TNSS Peak0-1h was significantly lower in those receiving combination treatment versus SCIT.  Transcriptomic analysis of nasal epithelial samples showed that treatment with the combination of SCIT/tezepelumab, but neither monotherapy, caused persistent down-regulation of a gene network related to type 2 inflammation that was associated with improvement in NAC responses.  The authors concluded that inhibition of TSLP augmented the effectiveness of SCIT during therapy and may promote tolerance after a 1-year course of treatment.

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References