ASTHMA IMMUNOMODULATORS

PRICING INFO


References:
MEPOLIZUMAB STUDIES


OMALIZUMAB STUDIES



RESLIZUMAB STUDIES


BENRALIZUMAB STUDIES



Drug Dosage form Dosage Generic/Price Mechanism / FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Benralizumab

Fasenra®
Prefilled syringe
  • 30 mg
  • Syringe should be refrigerated
Severe asthma with eosinophilic phenotype (≥ 12 years old)
  • Dosing: 30 mg subcutaneously once every 4 weeks for the first 3 doses, and then once every 8 weeks thereafter
  • Give in upper arm, thigh, or abdomen
  • Fasenra should be administered by a healthcare professional
  • Prior to administration, warm Fasenra by leaving carton at room temperature for about 30 minutes. Administer Fasenra within 24 hours or discard into sharps container.
NO/$$$$ Mechanism
  • IL-5 is the major cytokine responsible for the growth, differentiation, recruitment, activation, and survival of eosinophils
  • Benralizumab is a humanized IL-5 monoclonal antibody that directly binds to the alpha subunit of the human interleukin-5 receptor (IL-5Rα) that is expressed on the surface of eosinophils and basophils.
  • Benralizumab facilitates binding of immune effector cells, such as natural killer (NK) cells, leading to apoptosis of eosinophils and basophils through antibody-dependent cell-mediated cytotoxicity
  • Reduction in eosinophils is thought to decrease inflammation and improve asthma

FDA-approved indications
  • Asthma - add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. In trials eosinophilic phenotype was typically defined as blood eosinophils ≥ 300 cells/mcL
NOTE: P = % of patients on placebo who reported side effect. Only side effects that occurred at an incidence of ≥ 3% overall, and ≥ 1% more than placebo are listed

  • Headache - 8%, P - 6%
  • Pyrexia - 3%, P - 2%
  • Pharyngitis - 5%, P - 3%
  • No clinically relevant drug interactions have been identified
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis, angioedema, urticaria, and rash have been reported. Reactions typically occur within hours of administration, but may be delayed by days.
  • Acute asthma exacerbation - do not use to treat acute asthma exacerbations
  • Parasitic (Helminth) infections - benralizumab may suppress the immune response to helminth infections. Treat known helminth infections before starting benralizumab. If infection occurs during treatment and the patient does not respond to anti-helminth therapy, discontinue benralizumab.
  • Anti-benralizumab antibodies - in trials, 13% of patients developed anti-benralizumab antibodies during 48 - 56 weeks of treatment. Anti-benralizumab antibodies were associated with increased clearance of benralizumab and increased blood eosinophil levels. No evidence of an association of anti-benralizumab antibodies with efficacy or safety was observed.
  • Liver disease - has not been studied. Unlikely to affect elimination.
  • Kidney disease - has not been studied. Benralizumab is not cleared renally.
Drug Dosage form Dosage Generic/Price Mechanism / FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Mepolizumab

Nucala®
Single-dose vial
  • 100 mg
  • Must be reconstituted
  • Store below 25°C (77°F). Do not freeze.
Severe asthma with eosinophilic phenotype (≥ 12 years old)
  • Dosing: 100 mg subcutaneously every 4 weeks
  • Give in upper arm, thigh, or abdomen
  • Nucala should be administered by a healthcare professional

Eosinophilic granulomatosis with polyangiitis
(Churg-Strauss syndrome)
  • Dosing: 300 mg subcutaneously every 4 weeks
  • Give 3 separate 100 mg injections in upper arm, thigh, or abdomen
  • Administer at least 5 cm (approximately 2 inches) apart if more than 1 injection is administered at the same site
  • Nucala should be administered by a healthcare professional
NO/$$$$ Mechanism
  • IL-5 is the major cytokine responsible for the growth, differentiation, recruitment, activation, and survival of eosinophils
  • Mepolizumab is a humanized IL-5 antagonist monoclonal antibody
  • Mepolizumab binds IL-5 and prevents it from binding to its receptor on the surface of eosinophils. This decreases the inflammatory response seen in asthma.

FDA-approved indications
  • Asthma - add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype (typically defined in trials as blood eosinophils ≥ 150 cells/mcL within 6 weeks of dosing or ≥ 300 cells/mcL within 12 months of enrollment)
  • Eosinophilic granulomatosis with polyangiitis in adults - formerly known as Churg-Strauss syndrome
NOTE: P = % of patients on placebo who reported side effect. Only side effects that occurred at an incidence of ≥ 3% overall, and ≥ 1% more than placebo are listed

  • Headache - 19%, P - 18%
  • Injection site reactions - 8% of patients; reactions included pain, erythema, swelling, itching, and burning sensation
  • Back pain - 5%, P - 4%
  • Fatigue - 5%, P - 4%
  • Influenza - 3%, P - 2%
  • Urinary tract infection - 3%, P - 2%
  • Upper abdominal pain - 3%, P - 2%
  • Itching - 3%, P - 2%
  • Eczema - 3%, P - < 1%
  • Muscle spasms - 3%, P - < 1%

  • No clinically relevant drug interactions have been documented
  • Hypersensitivity reactions - hypersensitivity reactions including angioedema, bronchospasm, hypotension, urticaria, and rash have occurred. Reactions were typically seen within hours of administration, but may be delayed by days.
  • Acute asthma exacerbation - do not use to treat acute asthma exacerbations
  • Herpes zoster - rare cases of herpes zoster have occurred in patients receiving Nucala
  • Parasitic (Helminth) infections - mepolizumab may suppress the immune response to helminth infections. Treat known helminth infections before starting mepolizumab. If infection occurs during treatment and the patient does not respond to anti-helminth therapy, discontinue mepolizumab.
  • Anti-mepolizumab antibodies - in trials, 6% of patients developed anti-mepolizumab antibodies. It's unclear if antibody development is associated with reduced efficacy and/or an increased risk for hypersensitivity reactions.
  • Liver disease - has not been studied. Unlikely to affect elimination.
  • Kidney disease - has not been studied. Mepolizumab is not cleared renally.
Drug Dosage form Dosage Generic/Price Mechanism / FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Omalizumab

Xolair®
Single-use vial
  • 150 mg
  • Must be reconstituted
  • Store vials in refrigerator
Asthma (≥ 6 years old)
  • Omalizumab is given via subcutaneous injection every 2 - 4 weeks
  • Omalizumab dosing is based on pre-treatment IgE levels and body weight
  • Doses are adjusted for significant changes in body weight, but not IgE levels
  • A dosing table is available in the omalizumab PI under section 2 - omalizumab dosing tables
  • Omalizumab should be administered in a healthcare setting

Chronic idiopathic urticaria (≥ 12 years old)
  • Omalizumab 150 - 300 mg sub-Q every 4 weeks
  • Dosing in chronic idiopathic urticaria is not dependent on serum IgE or body weight
  • The appropriate duration of therapy has not been determined
NO/$$$$ Mechanism
  • Omalizumab is a recombinant DNA-derived humanized IgG1κ monoclonal antibody that selectively binds to human immunoglobulin E (IgE)
  • Omalizumab inhibits the binding of IgE to the high-affinity IgE receptor (FcεRI) on the surface of mast cells and basophils
  • Reduction in surface-bound IgE on FcεRI-bearing cells limits the degree of release of mediators of the allergic response

FDA-approved indications
  • Asthma - Omalizumab is indicated for patients 6 years of age and older with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids
  • Chronic idiopathic urticaria - in adults and adolescents (≥ 12 years) who remain symptomatic despite H₁ antihistamine treatment
NOTE: P = % of patients on placebo who reported side effect. Only side effects that occurred at an incidence of ≥ 3% overall, and more than placebo are listed. Data below is from asthma studies.

  • Injection site reactions - up to 45% of patients; reactions include bruising, redness, warmth, burning, stinging, itching, hive formation, pain, indurations, mass, and inflammation
  • Joint ache - 8%, P - 6%
  • Pain (general) - 7%, P - 5%
  • Leg pain - 4%, P - 2%
  • Fatigue - 3%, P - 2%
  • Dizziness - 3%, P - 2%

  • No clinically relevant drug interactions have been documented
  • Anaphylaxis - anaphylactic reactions have occurred in up to 0.2% of patients. Reactions may occur at any time during treatment. Patients with a history of anaphylaxis to foods, medications, and other causes may be at increased risk. Omalizumab should be administered in a healthcare setting.
  • Acute asthma exacerbation - do not use to treat acute asthma exacerbations
  • Cancers - malignant neoplasms were observed in 20 of 4127 (0.5%) omalizumab-treated patients compared with 5 of 2236 (0.2%) control patients in clinical studies. Cancers were of various types. A 5-year observational study found no increased risk of cancer (see FDA communication).
  • Syndrome of fever, joint pain, lymphadenopathy, and rash - has been seen in some patients 1 - 5 days after injection
  • Parasitic (Helminth) infections - omalizumab may increase the risk of geohelminthic infections (roundworm, hookworm, whipworm, threadworm) in patients at high-risk for these infections
  • Increased vascular events - omalizumab may increase the risk of cardio- and cerebrovascular events (see FDA communication). The increased risk, if any, is small. Causality has not been proven.
  • Serum IgE levels - serum IgE levels increase with omalizumab therapy and may remain elevated up to one year after stopping
  • Anti-omalizumab antibodies - anti-omalizumab antibodies were detected in approximately 1/1723 (< 0.1%) of patients. It's unclear if antibody development is associated with decreased efficacy and/or an increased risk of hypersensitivity reactions.
  • Liver disease - has not been studied
  • Kidney disease - has not been studied
Drug Dosage form Dosage Generic/Price Mechanism / FDA-approved indication Side Effects Drug Interactions Precautions / Contraindications
Reslizumab

Cinqair®
Single-use vial
  • 100 mg/10 ml (10 mg/ml)
  • Store vials in refrigerator
Severe asthma with eosinophilic phenotype (≥ 18 years old)
  • 3 mg/kg once every 4 weeks
  • Given as IV infusion over 20 - 50 minutes
NO/$$$$ Mechanism
  • Reslizumab is an interleukin-5 (IL-5) antagonist (IgG4, kappa)
  • IL-5 is the major cytokine responsible for the growth, differentiation, recruitment, activation, and survival of eosinophils. Eosinophils play an important role in the inflammatory component of asthma.
  • Reslizumab binds to IL-5 and blocks its binding to IL-5 receptors on eosinophils
  • By inhibiting IL-5 signaling, reslizumab reduces the production and survival of eosinophils

FDA-approved indications
  • Asthma - reslizumab is indicated for the add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophilic phenotype. In trials, eosinophilic phenotype was defined as blood eosinophil level ≥ 400 cells/μl.
NOTE: P = % of patients on placebo who reported side effect. Only side effects that occurred at a greater incidence than placebo are listed.

  • CPK elevations - 20%, P - 18%
  • Myalgia - 1%, P - 0.5%
  • Malignancy - 0.6%, P - 0.3%
  • Anaphylaxis - 0.3%, P - 0%
  • No clinically relevant drug interactions have been documented
  • Anaphylaxis - in trials, anaphylactic reactions occurred in 0.3% of reslizumab-treated patients. Reactions occurred during or within 20 minutes of an infusion and were reported as early as the second dose. Reslizumab should be administered in a healthcare setting.
  • Acute asthma exacerbation - do not use to treat acute asthma exacerbations
  • CPK elevations - in trials, transient CPK elevations occurred in 20% of reslizumab-treated patients compared to 18% of placebo-treated patients. Elevations > 10 X the upper limit of normal occurred in 0.8% of reslizumab-treated patients and 0.4% of placebo-treated patients.
  • Malignancies - malignancies were observed in 0.6% (6/1028) of reslizumab-treated patients compared with 0.3% (2/730) of placebo-treated patients. Malignancies were diverse in nature and a majority were diagnosed within 6 months of starting reslizumab.
  • Reduction of corticosteroids - no studies have been conducted to assess the reduction of corticosteroids after initiating reslizumab therapy. Use caution when reducing oral or inhaled steroids after starting reslizumab.
  • Parasitic (Helminth) infections - reslizumab may increase the risk of geohelminthic infections (roundworm, hookworm, whipworm, threadworm). Known helminth infections should be treated before initiating therapy. If patients become infected while on reslizumab and they do not respond to anti-helminth therapy, reslizumab should be stopped.
  • Anti-reslizumab antibodies - in trials, anti-reslizumab antibodies developed in up to 5.4% of reslizumab-treated patients. It's unknown if antibody development is associated with reduced efficacy and/or hypersensitivity reactions.
  • Liver disease - has not been studied
  • Kidney disease - has not been studied