Efficacy and Safety Profiles

CINQAIR has demonstrated improvements in 3 important clinical measures, with the flexibility of home infusion by an HCP.1-5

CINQAIR offers 3 options for HCP-controlled administration1-5:

HCP=healthcare professional; IL-5=interleukin-5.

Exacerbations (Studies I-II)

CINQAIR consistently helped prevent exacerbations vs placebo in multiple clinical trials over 52 weeks1,2

Reduction in
overall exacerbations

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  • Study I: 50% exacerbation reduction over 52 weeks (n=245, P<0.0001)

OCSs=oral (systemic) corticosteroids.

Reduction in exacerbations
requiring OCSs

  • Study I: 55% reduction in exacerbations requiring OCSs
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Study Design: Studies I-II1,2

Design: 52-week studies comparing treatment with CINQAIR or placebo along with background asthma therapy in 953 patients with severe asthma who were required to have a blood eosinophil count ≥400/mcL (within 3-4 weeks of dosing) and ≥1 asthma exacerbation requiring systemic corticosteroid use over the past 12 months. The majority of patients were on medium-high dose inhaled corticosteroids (ICSs) plus a long-acting beta agonist (LABA) at baseline. Maintenance OCSs were allowed. Primary Endpoint: Frequency of asthma exacerbations. Secondary Endpoints: Change from baseline in forced expiratory volume in one second (FEV1), blood eosinophil count, Asthma Control Questionnaire-7 (ACQ-7) score, and Asthma Quality of Life Questionnaire (AQLQ) total score. Exacerbation Definition: A worsening of asthma that required at least 1 of the following medical interventions: 1) Either the use of a systemic corticosteroid (if not already taking), or a ≥2-fold increase in the use of ICSs for 3 or more days, and/or 2) Asthma-related emergency treatment including at least 1 of the following: an unscheduled visit to their healthcare professional for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms; a visit to the emergency room for asthma-related treatment; or an asthma-related hospitalization.

Lung Function (Studies I-IV)

CINQAIR consistently improved lung function (FEV1) vs placebo across multiple studies1,4,6-8

Change from baseline over 16 weeks in Studies I-IV1,4,6-8
Consistent improvements in Studies I-III
IMPROVEMENT OVER 16 WEEKS

EOS=eosinophils; FEV1=forced expiratory volume in one second.

*Patients in Studies I-III were required to have a blood EOS ≥400/mcL within 3-4 weeks of dosing.

†Patients in Study IV were not selected for blood EOS levels. Approximately 20% of patients had a screening blood EOS ≥400 mcL within 3-4 weeks of dosing.

In a post hoc subgroup analysis of Study IV:

Lung function in patients with blood EOS ≥400/mcL1,5

Change in FEV1 by blood eosinophil threshold was prespecified in Study IV. The study was not adequately powered to test the efficacy of CINQAIR across multiple eosinophil subgroups. The magnitude of the treatment difference in the ≥400 cells/mcL subgroup appears to have been primarily influenced by a near complete lack of response in the small number of patients treated with placebo.1,5 Result was nonsignificant.

Statistical significance cannot be inferred and conclusions cannot be drawn from post hoc subgroup analyses

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Study Design: Studies I-II1,2

Design: 52-week studies comparing treatment with CINQAIR or placebo along with background asthma therapy in 953 patients with severe asthma who were required to have a blood eosinophil count ≥400/mcL (within 3-4 weeks of dosing) and ≥1 asthma exacerbation requiring systemic corticosteroid use over the past 12 months. The majority of patients were on medium-high dose inhaled corticosteroids (ICSs) plus a long-acting beta agonist (LABA) at baseline. Maintenance OCSs were allowed. Primary Endpoint: Frequency of asthma exacerbations. Secondary Endpoints: Change from baseline in forced expiratory volume in one second (FEV1), blood eosinophil count, Asthma Control Questionnaire-7 (ACQ-7) score, and Asthma Quality of Life Questionnaire (AQLQ) total score. Exacerbation Definition: A worsening of asthma that required at least 1 of the following medical interventions: 1) Either the use of a systemic corticosteroid (if not already taking), or a ≥2-fold increase in the use of ICSs for 3 or more days, and/or 2) Asthma-related emergency treatment including at least 1 of the following: an unscheduled visit to their healthcare professional for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms; a visit to the emergency room for asthma-related treatment; or an asthma-related hospitalization.

Study Design: Study III1,3

Design: 16-week study comparing treatment with CINQAIR or placebo in 315 patients with severe asthma with an eosinophilic phenotype (identified by blood eosinophil count ≥400/mcL within 3-4 weeks of dosing). The majority of patients were on regular treatment with medium-high dose ICSs plus a LABA. Maintenance OCSs were not allowed. Primary Endpoint: FEV1.

Study Design: Study IV1,4,5

Design: 16-week study comparing treatment with CINQAIR or placebo in 496 patients with severe asthma unselected for baseline blood eosinophil levels (~80% of patients had a screening blood eosinophil count <400/mcL within 3-4 weeks of dosing). The majority of patients were on regular treatment with medium-high dose ICSs plus a LABA. Maintenance OCSs were not allowed. Primary Endpoint: FEV1.

Quality of Life (Studies I-II)

CINQAIR improved quality of life in Studies I-II1,2

Based on the AQLQ (CINQAIR vs placebo):

  • Study I: 66% vs 58% (245 vs 244), respectively
  • Study II: 67% vs 55% (232 vs 232), respectively

Responder rate was defined as an improvement in score of 0.5 or more as threshold over 16 weeks.1,2

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Study Design: Studies I-II1,2

Design: 52-week studies comparing treatment with CINQAIR or placebo along with background asthma therapy in 953 patients with severe asthma who were required to have a blood eosinophil count ≥400/mcL (within 3-4 weeks of dosing) and ≥1 asthma exacerbation requiring systemic corticosteroid use over the past 12 months. The majority of patients were on medium-high dose inhaled corticosteroids (ICSs) plus a long-acting beta agonist (LABA) at baseline. Maintenance OCSs were allowed. Primary Endpoint: Frequency of asthma exacerbations. Secondary Endpoints: Change from baseline in forced expiratory volume in one second (FEV1), blood eosinophil count, Asthma Control Questionnaire-7 (ACQ-7) score, and Asthma Quality of Life Questionnaire (AQLQ) total score. Exacerbation Definition: A worsening of asthma that required at least 1 of the following medical interventions:

Peak Expiratory Flow

In an analysis of a post hoc exploratory endpoint in Study II:

CINQAIR effect on morning peak expiratory flow (PEF) after first dose and over 52 weeks9

Change from baseline in daily morning PEF in Study II9

Results were similar in Study I.9

Statistical significance cannot be inferred and conclusions cannot be drawn from a post hoc analysis of an exploratory endpoint

Post hoc subanalysis

This analysis assessed changes from baseline in PEF to evaluate Weeks 1-4, 7, and 52. Patients used a PEF meter and recorded their pre-dose (prior to use of long-acting beta agonists and inhaled corticosteroids) PEF daily throughout Studies I-II. PEF technique was reviewed at scheduled clinic visits. Weekly averages of daily morning PEF measurements are reported.9

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Study Design: Studies I-II1,2

Design: 52-week studies comparing treatment with CINQAIR or placebo along with background asthma therapy in 953 patients with severe asthma who were required to have a blood eosinophil count ≥400/mcL (within 3-4 weeks of dosing) and ≥1 asthma exacerbation requiring systemic corticosteroid use over the past 12 months. The majority of patients were on medium-high dose inhaled corticosteroids (ICSs) plus a long-acting beta agonist (LABA) at baseline. Maintenance OCSs were allowed. Primary Endpoint: Frequency of asthma exacerbations. Secondary Endpoints: Change from baseline in forced expiratory volume in one second (FEV1), blood eosinophil count, Asthma Control Questionnaire-7 (ACQ-7) score, and Asthma Quality of Life Questionnaire (AQLQ) total score. Exacerbation Definition: A worsening of asthma that required at least 1 of the following medical interventions: 1) Either the use of a systemic corticosteroid (if not already taking), or a ≥2-fold increase in the use of ICSs for 3 or more days, and/or 2) Asthma-related emergency treatment including at least 1 of the following: an unscheduled visit to their healthcare professional for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms; a visit to the emergency room for asthma-related treatment; or an asthma-related hospitalization.

Adverse Reactions

Adverse Reactions1

  • Severe adverse reactions that occurred more frequently in patients receiving CINQAIR than placebo included anaphylaxis (3 [0.3%] vs 0 [0.0%], respectively) and malignancy (6 [0.6%] vs 2 [0.3%], respectively)1
  • Oropharyngeal pain was the only side effect that occurred in ≥2% of patients receiving CINQAIR (reslizumab) Injection and more commonly than in patients receiving placebo (2.6% vs 2.2%, respectively)1
  • Elevated baseline creatine phosphokinase (CPK) was more frequent in patients randomized to CINQAIR (14%) versus placebo (9%). Transient CPK elevations in patients with normal baseline CPK values were observed more frequently with CINQAIR (20%) versus placebo (18%) during routine laboratory assessments
  • Myalgia was reported in 1% (10/1028) of patients in the CINQAIR 3 mg/kg group compared to 0.5% (4/730) of patients in the placebo group
  • Immunogenicity: In placebo-controlled studies, a treatment-emergent anti-reslizumab antibody response developed in 53/983 (5.4%) of CINQAIR-treated patients (3 mg/kg). The antibody responses were of low titer and often transient. There was no detectable impact of the antibodies on the clinical pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of CINQAIR
  • No adverse event exceeded placebo by more than 1% among those patients receiving CINQAIR10

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Responder Data

In a post hoc subgroup analysis of pooled data from Studies I-II:

Assessment of FEV1 in patients categorized as “super” and “early” responders with CINQAIR11

  • “Super” response = ≥300 mL or ≥500 mL increase from baseline in FEV1 at any post-baseline time point during the 52 weeks of treatment with CINQAIR
  • “Early” response = ≥100 mL increase from baseline in FEV1 at 4 weeks after the first dose of CINQAIR
Proportion of patients who achieved “super”
response at each 4-week time point11

≥300 mL increase from baseline

Within the first 4 weeks of the first dose, 45.7% of CINQAIR patients saw a “super”
response (150 of 328 patients) vs ~34% of placebo patients (~95 of 281 patients)

  • Of the patients who saw a ≥500 mL increase during the duration of the study, 37.6% of CINQAIR patients saw this “super” response within 4 weeks of the first dose (83 of 221 patients) vs ~26% of placebo patients (~49 of 189 patients)11
  • At 4 weeks, 54% of CINQAIR patients were FEV1> early responders vs 39% of placebo patients in the overall study population11

Statistical significance cannot be inferred and conclusions cannot be drawn from a post hoc analysis of an exploratory endpoint

FEV1=forced expiratory volume in one second.

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Study Design: Studies I-II1,2

Design: 52-week studies comparing treatment with CINQAIR or placebo along with background asthma therapy in 953 patients with severe asthma who were required to have a blood eosinophil count ≥400/mcL (within 3-4 weeks of dosing) and ≥1 asthma exacerbation requiring systemic corticosteroid use over the past 12 months. The majority of patients were on medium-high dose inhaled corticosteroids (ICSs) plus a long-acting beta agonist (LABA) at baseline. Maintenance OCSs were allowed. Primary Endpoint: Frequency of asthma exacerbations. Secondary Endpoints: Change from baseline in forced expiratory volume in one second (FEV1), blood eosinophil count, Asthma Control Questionnaire-7 (ACQ-7) score, and Asthma Quality of Life Questionnaire (AQLQ) total score. Exacerbation Definition: A worsening of asthma that required at least 1 of the following medical interventions: 1) Either the use of a systemic corticosteroid (if not already taking), or a ≥2-fold increase in the use of ICSs for 3 or more days, and/or 2) Asthma-related emergency treatment including at least 1 of the following: an unscheduled visit to their healthcare professional for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms; a visit to the emergency room for asthma-related treatment; or an asthma-related hospitalization.

New Systemic Corticosteroid Prescriptions

In a post hoc analysis of pooled data from Studies I-II:

New systemic corticosteroid (SCS) prescriptions for asthma and/or clinical asthma exacerbation12

Mean cumulative SCS doses (mg) per patient (IV, intramuscular, or oral)
  • Approximately 70.6% of patients receiving CINQAIR had no new SCS prescriptions vs 52.1% of patients receiving placebo12
  • In patients receiving CINQAIR, 248 patients received new SCS prescriptions indicated for CAEs vs 480 in patients receiving placebo12
  • The total cumulative SCS dose (mg) was 121,135 in patients taking CINQAIR vs 290,977 in patients taking placebo12

Statistical significance cannot be inferred and conclusions cannot be drawn from a post hoc analysis of an exploratory endpoint

CAEs=clinical asthma exacerbations; IV=intravenous; SE=standard error.

Post hoc analysis

Data were pooled from 2 studies that assessed the effect of CINQAIR on cumulative SCS burden during a 52-week treatment period compared with placebo in the overall study population. In the overall population (N=953), 228 (48%) of patients in the placebo group and 140 (29%) of patients in the CINQAIR group were prescribed SCS for asthma and/or CAE after the first dose of study drug/placebo through to the end of the study. New prescriptions for SCS (IV, intramuscular, or oral) indicated for cases of clinical asthma exacerbations and/or for asthma with a start date after the first dose of study drug were counted.12

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Study Design: Studies I-II1,2

Design: 52-week studies comparing treatment with CINQAIR or placebo along with background asthma therapy in 953 patients with severe asthma who were required to have a blood eosinophil count ≥400/mcL (within 3-4 weeks of dosing) and ≥1 asthma exacerbation requiring systemic corticosteroid use over the past 12 months. The majority of patients were on medium-high dose inhaled corticosteroids (ICSs) plus a long-acting beta agonist (LABA) at baseline. Maintenance OCSs were allowed. Primary Endpoint: Frequency of asthma exacerbations. Secondary Endpoints: Change from baseline in forced expiratory volume in one second (FEV1), blood eosinophil count, Asthma Control Questionnaire-7 (ACQ-7) score, and Asthma Quality of Life Questionnaire (AQLQ) total score. Exacerbation Definition: A worsening of asthma that required at least 1 of the following medical interventions: 1) Either the use of a systemic corticosteroid (if not already taking), or a ≥2-fold increase in the use of ICSs for 3 or more days, and/or 2) Asthma-related emergency treatment including at least 1 of the following: an unscheduled visit to their healthcare professional for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms; a visit to the emergency room for asthma-related treatment; or an asthma-related hospitalization.

Exposure and Efficacy Measures Across Body Weights

Based on a post hoc subgroup analysis of Study I:

Steady-state exposures across a range of body weights13

Weight and plasma concentrations at Week 4813

Statistical significance cannot be inferred and conclusions cannot be drawn from post hoc analyses

Post hoc analysis

A population pharmacokinetic model was developed to characterize the disposition of CINQAIR and to evaluate the influence of key covariates, including body weight, on steady-state exposures of CINQAIR. Weight and plasma concentrations were assessed at Week 48 by weight quartiles (≤61 kg, 62-74 kg, >74-86 kg, and >86 kg), based on a subset of data (N=216) from Study I.13

Based on a post hoc subgroup analysis of patients stratified by weight from Studies I-II:

Efficacy measures in high-weight and low-weight patients14

Change from baseline vs placebo in 4 separate measures over 52 weeks14

* P=Not significant.

† All measures vs placebo.

Results were similar in GINA Step 4 and 5 patients.

Statistical significance cannot be inferred and conclusions cannot be drawn from post hoc analyses

Post hoc subgroup analysis

Patients were analyzed by weight category (<70 kg or ≥70 kg) in a post hoc analysis of 2 randomized, 52-week, placebo-controlled, Phase III trials of CINQAIR patients on at least medium-dose ICSs at baseline. CAEs and change in FEV1, ACQ, and AQLQ were studied in the overall population and GINA Step 4/5 subgroup at 52 weeks. Results are descriptive only.14

ACQ=Asthma Control Questionnaire; AQLQ=Asthma Quality of Life Questionnaire; CAEs=clinical asthma exacerbations; FEV1=forced expiratory volume in one second; GINA=Global Initiative for Asthma Guidelines; ICSs=inhaled corticosteroids.

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Study Design: Studies I-II1,2

Design: 52-week studies comparing treatment with CINQAIR or placebo along with background asthma therapy in 953 patients with severe asthma who were required to have a blood eosinophil count ≥400/mcL (within 3-4 weeks of dosing) and ≥1 asthma exacerbation requiring systemic corticosteroid use over the past 12 months. The majority of patients were on medium-high dose inhaled corticosteroids (ICSs) plus a long-acting beta agonist (LABA) at baseline. Maintenance OCSs were allowed. Primary Endpoint: Frequency of asthma exacerbations. Secondary Endpoints: Change from baseline in forced expiratory volume in one second (FEV1), blood eosinophil count, Asthma Control Questionnaire-7 (ACQ-7) score, and Asthma Quality of Life Questionnaire (AQLQ) total score. Exacerbation Definition: A worsening of asthma that required at least 1 of the following medical interventions: 1) Either the use of a systemic corticosteroid (if not already taking), or a ≥2-fold increase in the use of ICSs for 3 or more days, and/or 2) Asthma-related emergency treatment including at least 1 of the following: an unscheduled visit to their healthcare professional for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms; a visit to the emergency room for asthma-related treatment; or an asthma-related hospitalization.

REFERENCES: 1. CINQAIR Prescribing Information. West Chester, PA. Teva Respiratory, LLC. 2. Castro M, Zangrilli J, Wechsler ME, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015;3(5):355-366. 3. Bjermer L, Lemiere C, Maspero J, Weiss S, Zangrilli J, Germinaro M. Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels: a randomized phase 3 study. Chest. 2016;150(4):789-798. 4. Data on file (clinical study report: a 16-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of reslizumab [3.0 mg/kg] treatment in patients with moderate to severe asthma. Study C38072/3084). Parsippany, NJ. Teva Respiratory, LLC. February 2015. 5. Corren J, Weinstein S, Janka L, Zangrilli J, Garin M. Phase 3 study of reslizumab in patients with poorly controlled asthma: effects across a broad range of eosinophil counts. Chest. 2016;150(4):799-810. 6. Data on file (clinical study report: a 12-month, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of reslizumab [3.0 mg/kg] in the reduction of clinical asthma exacerbations in patients [12-75 years of age] with eosinophilic asthma. Study C38072/3082). Parsippany, NJ. Teva Respiratory, LLC. January 2015. 7. Data on file (clinical study report: a 12-month, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of reslizumab [3.0 mg/kg] in the reduction of clinical asthma exacerbations in patients [12-75 years of age] with eosinophilic asthma. Study C38072/3083). Parsippany, NJ. Teva Respiratory, LLC. February 2015. 8. Data on file (clinical study report: a 16-week, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of reslizumab [0.3 or 3.0 mg/kg] as treatment for patients [12-75 years of age] with eosinophilic asthma. Study C38072/3081). Parsippany, NJ. Teva Respiratory, LLC. January 2015. 9. Bernstein D, Hickey L, Garin M. Poster presented at: American College of Allergy, Asthma & Immunology Conference; November 15-19, 2018; Seattle, WA. 10. Data on file (Clinical Study Report: Summary of Clinical Safety). Parsippany, NJ: Teva Respiratory, LLC. 11. Virchow JC, Hickey L, Du E, Garin M. FEV1 early response (ER) and super-response (SR) with reslizumab (RES) in eosinophilic asthma. Poster presented at: the ERS Annual Meeting; 28 September–2 October 2019; Madrid, Spain. 12. Nair P, Bardin P, Humbert M, et al. Efficacy of intravenous reslizumab in oral corticosteroid-dependent asthma. J Allergy Clin Immunol Pract. 2020;8(2):555-564. 13. Jaworowicz D, Fiedler-Kelly J, Rabinovich-Guilatt L, Bond M. The steady-state pharmacokinetic profile across a range of patient body weight categories supports weight-based dosing for intravenous reslizumab. Poster presented at: The American Thoracic Society (ATS) International Congress; May 13-18, 2016; San Francisco, CA. 14. Murphy K, Noble R, Hickey L, Garin M. Efficacy of weight-based reslizumab dosing is consistent across body weights in post-hoc analysis. Poster presented at: ESR International Congress; September 15-19, 2018; Paris, France.