ONSCREEN TEXT:
NUCALA (mepolizumab) Efficacy and Safety for Patients With Severe Eosinophilic Asthma
DR. GOLDMAN:
Hi, I’m Dr. Yaron Goldman, a critical care pulmonologist.
I will discuss the efficacy and safety data of NUCALA (mepolizumab) for patients with severe eosinophilic asthma.
First, let’s review the Indications and Important Safety Information for NUCALA.
ONSCREEN TEXT:
INDICATIONS AND IMPORTANT SAFETY INFORMATION
SEA
add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype. NUCALA is not indicated for the relief of acute bronchospasm or status asthmaticus.
CRSwNP
add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients 18 years of age and older with inadequate response to nasal corticosteroids.
EGPA
treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).
HES
treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) for greater than or equal to 6 months without an identifiable nonhematologic secondary cause.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
Known hypersensitivity to mepolizumab or excipients.
Additional Important Safety Information will be presented later in this video.
Please see full Prescribing Information and Patient Information for NUCALA at the adjacent links or visit NucalaHCP.com.
NUCALA injection is available as a 100-mg/mL vial, autoinjector, and prefilled syringe.
NARRATOR:
NUCALA is indicated for the:
- add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype. NUCALA is not indicated for the relief of acute bronchospasm or status asthmaticus.
- add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients 18 years of age and older with inadequate response to nasal corticosteroids.
- treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).
- treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) for greater than or equal to 6 months without an identifiable nonhematologic secondary cause.
Contraindications: Known hypersensitivity to mepolizumab or excipients.
ONSCREEN TEXT:
IMPORTANT SAFETY INFORMATION (cont’d)
WARNINGS AND PRECAUTIONS.
Hypersensitivity Reactions:
Hypersensitivity reactions (eg, anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred with NUCALA. These reactions generally occur within hours of administration but can have a delayed onset (ie, days). Discontinue if a hypersensitivity reaction occurs.
Acute Asthma Symptoms or Deteriorating Disease: NUCALA should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.
Opportunistic Infections: Herpes Zoster: Herpes zoster infections have occurred in patients receiving NUCALA. Consider vaccination if medically appropriate.
Please see Important Safety Information for NUCALA throughout this video.
Please see full Prescribing Information and Patient Information for NUCALA at the adjacent links or visit NucalaHCP.com.
NARRATOR:
IMPORTANT SAFETY INFORMATION continued
WARNINGS AND PRECAUTIONS. Hypersensitivity Reactions:
Hypersensitivity reactions (for example, anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred with NUCALA. These reactions generally occur within hours of administration but can have a delayed onset (that is, days). Discontinue if a hypersensitivity reaction occurs.
Acute Asthma Symptoms or Deteriorating Disease: NUCALA should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.
Opportunistic Infections: Herpes Zoster: Herpes zoster infections have occurred in patients receiving NUCALA. Consider vaccination if medically appropriate.
ONSCREEN TEXT:
IMPORTANT SAFETY INFORMATION (cont’d)
WARNINGS AND PRECAUTIONS (cont’d)
Reduction of Corticosteroid Dosage: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with NUCALA. Decreases in corticosteroid doses, if appropriate, should be gradual and 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.
Parasitic (Helminth) Infection: Treat patients with pre-existing helminth infections before initiating therapy with NUCALA. If patients become infected while receiving NUCALA and do not respond to anti-helminth treatment, discontinue NUCALA until infection resolves.
Additional Important Safety Information for NUCALA will be presented later in this video.
Please see full Prescribing Information and Patient Information for NUCALA at the adjacent links or visit NucalaHCP.com.
NARRATOR:
Reduction of Corticosteroid Dosage: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with NUCALA. Decreases in corticosteroid doses, if appropriate, should be gradual and 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.
Parasitic (Helminth) Infection: Treat patients with pre-existing helminth infections before initiating therapy with NUCALA. If patients become infected while receiving NUCALA and do not respond to anti-helminth treatment, discontinue NUCALA until infection resolves.
Additional Important Safety Information will be presented later in this video.
ONSCREEN TEXT:
Exacerbation Reduction Evaluated in a Controlled Clinical Trial and Real-World Study
Trial 2: Confirmatory Exacerbation1,2
Patients aged ≥12 years with SEA, ≥2 exacerbations* in the previous year, BEC ≥150 cells/μL†
32 Weeks (treatment Q4W + SOC)
NUCALA (mepolizumab) 100 mg SC + placebo IV (n=194)
Mepolizumab 75 mg IV + placebo SC (n=191)
Placebo IV + placebo SC (n=191)
Primary endpoint: annualized exacerbation* rate
REALITI-A: Real-World Study2‡
2-year, prospective, observational study assessing efficacy and safety of NUCALA Q4W in adults with SEA initiating NUCALA
NUCALA 100 mg SC (N=822)
Study limitations: Real-world studies evaluate associations and do not establish causality.
Limitations important when interpreting results: no comparator arm; differences in patient
populations; and data collection vs controlled trials.
Primary objective: annualized exacerbation* rate
Safety (N=823): drug-related AEs (11%) and SAEs (<1%); most common AE was headache (4%)
SOC=high-dose ICS plus additional controller(s) with or without OCS.
Safety population at 2-year analysis (n=823). 27% of patients discontinued NUCALA (2% due to an AE). Patients included were from Europe (n=665), the US (n=100), and Canada (n=57).
*Defined as the worsening of asthma that requires systemic corticosteroids, hospitalization, or an ED visit or requires at least double the existing maintenance systemic corticosteroid dose for ≥3 days.
†At baseline or ≥300 cells/μL within the last 12 months.
‡Data collected prospectively at usual appointments. One year of prior medical data were collected retrospectively at enrollment from medical records and patient recall.
DR. GOLDMAN:
Asthma exacerbation and oral corticosteroid reductions were evaluated in numerous studies for NUCALA.
Asthma exacerbation reductions were evaluated in a controlled 32-week clinical trial, known as Trial 2, where enrolled patients were ages 12 and older and had severe asthma with a blood eosinophil count of at least 150 cells at baseline, or at least 300 cells in the past 12 months. Their background therapy consisted of a traditional high-dose ICS plus another controller with or without OCS. In the treatment arms, patients received either mepolizumab 75 mg IV, NUCALA 100 mg subcue, or placebo every 4 weeks, all added to their background therapy.
The primary endpoint for Trial 2 was annualized exacerbation rate. Asthma exacerbations were also the primary measure studied in REALITI-A, a 2-year, prospective, observational study in adults with SEA starting NUCALA in a real-world setting.
Patients were from Europe, the United States, and Canada.
Of the 823 patients, drug-related adverse events occurred in 11% of patients and serious adverse events occurred in less than 1% of patients. The most common adverse event was headache at 4%.
Twenty-seven percent of patients discontinued NUCALA during the 2 years, including 2% due to an AE.
Please note the study limitations of REALITI-A: real-world studies evaluate associations and do not establish causality. Limitations are important when interpreting results because there is no comparator arm and there are differences in patient populations and data collection versus controlled trials.
ONSCREEN TEXT:
NUCALA (mepolizumab) Reduced Exacerbations1,2
Significant Exacerbation Reduction in a Clinical Trial (Trial 2)1
Primary Endpoint at Week 32
[Bar chart with mean rate of exacerbation per year for NUCALA (0.83, n=194) and placebo
(1.74, n=191). 53% reduction in exacerbation with NUCALA vs placebo. (P<0.001)]
Exacerbation Reduction in a Real-World Study (REALITI-A)2§
[Bar chart with rate of exacerbation per year for NUCALA post-exposure at 1 year‖ (1.24, n=820), postexposure at 2 years¶¶¶ (1.11, n=820) and 1-year‖ preexposure (4.29, n=821). 71% reduction at 1 year post-exposure (rate ratio 0.29; 95% CI: 0.26, 0.32) and 74% reduction at 2 years post-exposure (rate ratio 0.26; 95% CI: 0.24, 0.29) vs 1 year pre-exposure.]
Results are descriptive.
§Real-world study limitations: interpret results using limitations in study design.
‖Based on 1-year analysis model.
¶¶¶Based on 2-year analysis model.
DR. GOLDMAN:
In Trial 2, the primary endpoint was met, and data showed a significant reduction in exacerbations, where the exacerbation rate was reduced by 53% with NUCALA compared with placebo at Week 32. The annualized rates were 1.74 with placebo and 0.83 with NUCALA.
In REALITI-A, 1 year after NUCALA was initiated, patients experienced 71% fewer exacerbations compared to baseline.
Additionally, 2 years following NUCALA initiation, patients experienced 74% fewer exacerbations compared to baseline.
The results from the REALITI-A study are descriptive and should be interpreted using the limitations discussed earlier.
ONSCREEN TEXT:
NUCALA (mepolizumab) Reduced Exacerbations Requiring Hospitalization/ED Visit1-3
Significant Reduction in Exacerbations Requiring Hospitalization/ED Visit in a Clinical Trial (Trial 2)1
Secondary Endpoint at Week 32
[Bar chart with mean rate of exacerbation per year for NUCALA (0.08, n=194) and placebo (0.20, n=191). 61% reduction in exacerbation with NUCALA vs placebo (P=0.02).]
Reduction in Exacerbations Requiring Hospitalization/ED Visit in a Real-World Study (REALITI-A)2¶
Secondary Objectives
[Bar chart with rate of exacerbation per year for NUCALA post-exposure at 1 year# (0.23, n=820), post-exposure at 2 years### (0.19, n=820) and 1-year# pre-exposure (0.94, n=821). 76% reduction at 1 year post exposure (rate ratio 0.24; 95% CI: 0.20, 0.29) and 79% reduction at 2 years post-exposure (rate ratio 0.21; 95% CI: 0.17, 0.25) vs 1 year pre-exposure.]
Results are descriptive.
¶Real-world study limitations: interpret results using limitations in study design.
#Based on 1-year analysis model.
###Based on 2-year analysis model.
DR. GOLDMAN:
Additionally, in Trial 2, exacerbations requiring hospitalization or emergency visits were significantly reduced by 61% with NUCALA compared to placebo at Week 32.
In REALITI-A, 1 year after NUCALA was initiated, patients experienced 76% fewer exacerbations requiring hospitalization or an ED visit versus baseline.
Additionally, 2 years after NUCALA was initiated, patients experienced 79% fewer exacerbations requiring hospitalization or an ED visit versus baseline.
Results from the real-world study are descriptive and should be interpreted using the limitations discussed earlier.
ONSCREEN TEXT:
OCS Reduction With NUCALA (mepolizumab) Was Evaluated in a Clinical Trial and an Extension Study2,4,5
Trial 3: Confirmatory Daily OCS Reduction Trial (N=135)4
Select Inclusion Criteria:
- Age ≥12 years
- Daily maintenance OCS**
- Baseline BEC ≥150 cell/μL††
24 weeks (treatment Q4W + SOC)
NUCALA 100 mg SC (n=66)
Placebo SC (n=69)
SOC=high-dose ICS plus additional controller(s) with OCS** to maintain asthma control.
Primary endpoint: patients treated with NUCALA achieved significantly greater reductions in daily OCS dose (Weeks 20-24) while maintaining asthma control vs placebo (P=0.008).
OLE Study (N=651)2,5
OLE study included patients continuing from Trial 2 (91%) and Trial 3 (93%)
52 weeks (treatment Q4W + SOC)
NUCALA 100 mg SC
SOC=high-dose ICS plus additional controller(s).
Primary endpoint/results: long-term safety, including AEs and SAEs. Most frequent AEs (≥10%): nasopharyngitis, 30%; upper respiratory infection, 16%; asthma‡‡, 14%; headache, 14%; bronchitis, 12%; and sinusitis, 10%. The only SAE that occurred in ≥1% of patients was asthma.‡‡
**Defined as 5 to 35 mg of prednisone or equivalent per day.
††During optimization or ≥300 cells/μL within the last 12 months.
‡‡Indicates worsening or exacerbation of asthma.
DR. GOLDMAN:
OCS reduction with NUCALA was evaluated in Trial 3 and an extension study.
Trial 3 was a 24-week, confirmatory daily OCS reduction trial that enrolled patients aged 12 years and older with SEA who were on daily-maintenance OCS. During an optimization phase, patients were brought down to the lowest OCS dose that kept their asthma controlled in order to improve the rigor of the study. Patients were then randomized to receive NUCALA or placebo as add-on therapy, and then OCS was reduced according to a reduction protocol and maintained at that dose unless asthma control worsened.
The primary endpoint, at Weeks 20 to 24, was percent reduction in daily OCS dose while maintaining asthma control. NUCALA achieved significantly greater reductions in daily OCS dose while maintaining asthma control versus placebo, with a P value equal to 0.008.
Next, an open-label extension study was a 52-week study assessing the safety and efficacy of NUCALA in patients with SEA who completed Trial 2 (91%) and Trial 3 (93%).
The most common adverse events reported included nasopharyngitis, upper respiratory infection, worsening of asthma, headache, bronchitis, and sinusitis. The only serious adverse event occurring in greater than or equal to 1% of patients was worsening asthma.
The study showed that the side effect profile in the long term was similar to that seen in controlled studies.
ONSCREEN TEXT:
NUCALA (mepolizumab): Reduction in OCS Dose
Durability of OCS Reduction5§§
[Line graph showing median OCS dose results in mg per day for placebo + SOC (double blind, n=58), NUCALA + SOC (open-label, placebo in double blind, n=58), and NUCALA + SOC (double blind and open-label, n=57) during Trial 3 in the first 24 weeks and in the OLE study for the following 52 weeks. All patients received NUCALA during the open-label portion (Weeks 24- 76). The median daily OCS dose for the group receiving placebo during the double-blind phase was 12.3 mg at Baseline, 10 mg at Week 24, and 5 mg at Week 76. The median daily OCS dose for the group receiving NUCALA during the open-label phase was 10 mg at Baseline, 2.5 mg at Week 24, and 2.5 mg at Week 76.]
Post hoc analysis. All results are descriptive.
OCS reduction method in the open-label study was at clinician discretion.
§§Durability of response was defined as OCS dose reduction when combined with Trial 3 data. Graph includes only patients who completed the OLE study.
Graph reprinted from Lugogo N, et al. Clin Ther. 2016;38(9):2058-2070, Copyright 2016, with permission from Elsevier.
DR. GOLDMAN:
What about durability of reduction in steroids?
If we look at Trial 3 and then the open-label extension study, this post-hoc analysis showed sustained durability of the reduction in OCS for an additional 52 weeks for patients previously on NUCALA. We can also see that those patients previously on placebo received a lower steroid dose after starting NUCALA. Note that OCS was reduced during the open-label extension at clinical discretion, not by protocol.
Results from this post hoc analysis of Trial 3 and the open-label extension are descriptive.
ONSCREEN TEXT:
NUCALA (mepolizumab): Reduction in OCS Dose - Real-World Data
Real-World Study: Daily Maintenance OCS Dose‖ in a Subgroup of OCS-Dependent Patients2
[line graph with data from the REALITI-A study, shows the median maintenance OCS dose in the OCS-dependent patient subgroup, was reduced by 75% at Weeks 45 to 64 and showed further reduction by 100% at Weeks 81 to 104. The median daily OCS dose was 10 mg at Baseline, 2.5 mg at Weeks 45-64, and 0 mg at Weeks 81-104.1
Secondary endpoint. Results are descriptive.
Real-world study limitations: interpret results using limitations in study design.
‖Baseline maintenance OCS dose was defined as the average daily dose in the 28 days prior to the treatment index. Dose assessments were based on data captured from medical records or patient recall without documentation of asthma control.
DR. GOLDMAN:
If we look at the data from the REALITI-A study, the median maintenance OCS dose in the OCS-dependent patient subgroup was reduced by 75% at Weeks 45 to 64 and showed further reduction by 100% at Weeks 81 to 104.
Keep in mind again, these results are descriptive. Please interpret real-world study results using limitations previously discussed in study design.
ONSCREEN TEXT:
OCS Elimination
Trial 3: 14% of NUCALA (mepolizumab) patients vs 8% of placebo patients completely
eliminated daily OCS while maintaining asthma control4
Real-World Study of NUCALA:
In an OCS-dependent patient subgroup, 57% of patients discontinued daily maintenance OCS use¶¶ at 2 years (n=95/168; Weeks 101-104)2
Secondary objective. Results are descriptive.
Real-world study limitations: interpret results using limitations in study design.
¶¶Baseline maintenance OCS dose (prednisone equivalent mg/day) defined as average daily dose in the 28 days prior to the treatment index. Dose assessments were based on data captured from medical records or patient recall without documentation of asthma control.
DR. GOLDMAN:
Note in Trial 3, 14% of patients at Weeks 20 to 24 on NUCALA were able to completely eliminate daily OCS use while maintaining asthma control versus 8% of placebo patients.
In REALITI-A, 57% of patients discontinued daily maintenance OCS use at 2 years (n=95/168).
The real-world study results are descriptive and should be interpreted with the limitations presented earlier.
ONSCREEN TEXT:
Adverse Reactions (AR) in SEA
ARs ≥3% (and more common than placebo) in the first 24 weeks of Trial 2 and Trial 3
[table] AR(%): NUCALA (mepolizumab) (n=263); Placebo (n=257)
Headache: 19; 18
Injection-site reaction: 8; 9
Back pain: 5; 4
Fatigue: 5; 4
Influenza: 3; 2
Urinary tract infection: 3; 2
Upper abdominal pain: 3; 2
Pruritus: 3; 2
Eczema: 3; <1
Muscle spasms: 3; <1
Systemic Reactions, Including Hypersensitivity Reactions:
In 3 clinical trials, the percentage of participants who experienced systemic reactions was 3% with NUCALA and 5% with placebo. Manifestations included rash, pruritus, headache, myalgia, and flushing. The majority of systemic reactions were experienced on the day of dosing.
Injection-site reactions (eg, pain, erythema, swelling, itching, and/or burning sensation) occurred in participants treated with NUCALA.
Immunogenicity: Across clinical trials in patients aged >6 years receiving NUCALA, 6% developed anti-mepolizumab antibodies and 1 patient had neutralizing antibodies detected. The clinical relevance of anti-mepolizumab antibodies is not known.
DR. GOLDMAN:
This table shows the most common adverse reactions with NUCALA with an incidence of 3% or greater (and more common than placebo) reported in the first 24 weeks of Trial 2 and Trial 3. They include headache, injection-site reaction, back pain, fatigue, influenza, urinary tract infection, upper abdominal pain, pruritus, eczema, and muscle spasms.
In 3 clinical trials, 3% of patients who received NUCALA experienced systemic reactions compared to 5% in the placebo group. Manifestations included rash, pruritus, headache, myalgia, and flushing, and a majority of these were experienced on the first day of dosing. Also, note that patients receiving NUCALA experienced more injection-site reactions than those in the placebo group.
Across clinical trials in patients aged greater than or equal to 6 years receiving NUCALA, 6% developed anti-mepolizumab antibodies and 1 patient had neutralizing antibodies detected. The clinical relevance of anti-mepolizumab antibodies is not known.
ONSCREEN TEXT:
4.5-Year Open-Label Safety and Efficacy Study2,6,7
[Figure with Trial 1 and Open-Label, Long-Term Safety Study. Patients in Trial 1 were required to undergo a ≥12-month washout period and meet eligibility criteria to enroll in the Open-Label, Long-Term Safety Study.
Trial 1: 52-week study comparing mepolizumab IV (75, 250, or 750 mg) with placebo IV added to SOC in 616 patients aged ≥12 years with severe asthma and ≥2 exacerbations in the previous year.
Primary endpoint results: exacerbations/year, 1.24 with mepolizumab 75 mg IV vs 2.40 with placebo (48% reduction; P<0.0001)7.
Open-Label, Long-Term Safety Study (N=347) with NUCALA 100 mg SC every 4 weeks## + asthma controller therapy.
There were fewer patients over the course of the study: Baseline, n=347; Year 1, n=322; Year 2, n=301; Year 3, n=275; Year 4, n=157; Year 4.5, n=5.
Primary endpoint results: long-term safety, including AEs, serious AEs, and immunogenicity.
Most frequent AEs viral upper respiratory tract infection, 49%; headache, 29%; asthma,*** 27%; upper respiratory tract infection, 23%; and bronchitis, 21%.
Serious AEs in >1% of patients: 10%, and pneumonia, 2%. Positive antidrug antibody results, with no neutralizing antibodies, occurred in 8% of patients.†††
The long-term (≤4.5 years) safety and immunogenicity profile of NUCALA was similar to that seen in controlled asthma trials.]
##Patients continued in open-label, long-term safety study until a protocol-defined stopping criterion was met.
***The worsening or exacerbation of asthma.
†††The clinical relevance of the presence of anti-mepolizumab antibodies is unknown.
DR. GOLDMAN:
NUCALA was also evaluated long-term in a 4.5-year open-label safety and efficacy study.
Let’s first look at how patients got into the open-label, long term safety study. They started with a dose-ranging and exacerbation study, or Trial 1, in which 616 patients with severe asthma were enrolled. They were treated with an add-on mepolizumab IV or placebo for 52 weeks. After at least a 12-month washout—where they didn’t receive mepolizumab—347 eligible patients were then enrolled into the open-label long-term safety study and received NUCALA 100 mg subcutaneously added to their asthma controller therapy. There were fewer patients over the course of the study, as shown.
The long-term safety and immunogenicity profile of NUCALA up to 4.5 years was similar to controlled asthma trials.
The most frequent AEs were viral upper respiratory tract infection, headaches, asthma, upper respiratory tract infection, and bronchitis.
The most frequent serious AEs were worsening of asthma and pneumonia. Note that positive anti-drug antibodies occurred in 8% of patients but with no neutralizing antibodies.
ONSCREEN TEXT:
NUCALA (mepolizumab): Reduction in Exacerbations Over 4.5 Years2,6
4.5-Year Open-Label Study
[Bar chart with mean rate of exacerbations per year‡‡‡ for NUCALA + asthma controller therapy§§§ 4.5 years post-exposure (0.68, n=347; secondary endpoint) and asthma controller therapy§§§ during off-treatment period between Trial 1 and long-term safety study (1.74, n=347). 61% reduction in annual exacerbation rate.]
Select secondary endpoints: annualized exacerbation rate: 0.68; 95% CI: 0:60, 0.78. Mean change in ACQ-5 score from baseline: -0.47 points at Week 12 and end of study. Mean change in prebronchodilator FEV1 from baseline: 124 mL at Week 12; gradually decreased to approximate baseline values at end of study.
‡‡‡Based on exacerbations reported from the time a patient enrolled in the open-label, longterm safety study until study withdrawal (the median duration was 3.8 years).
§§§Required to be on ≥1 asthma controller medication for ≥12 weeks prior to study start.
All results are descriptive.
DR. GOLDMAN:
Over 4.5 years, NUCALA was associated with protection from exacerbations. Patients on NUCALA + asthma controller therapy had a 61% reduction in an annual exacerbation rate 4.5 years post-exposure in the open-label study. The annualized rates were 1.74 prior to the study and 0.68 post-NUCALA exposure. The median study duration was 3.8 years.
Results are descriptive.
ONSCREEN TEXT:
NUCALA (mepolizumab): Patients with Zero Exacerbations Over 4.5 Years2
4.5-Year Open-Label Study Number of Exacerbations§§§
All Patients, N=347
[Pie chart showing distribution of patients (n=347) by number of exacerbations over the 4.5 year study period: 0 (33%); 1 (20%); 2 (12%); 3 (8%); 4 (6%) ≥5 (20%).]
Results are descriptive.
§§§Based on exacerbations reported from the time a patient enrolled until study withdrawal.
The median duration was 3.8 years.
DR. GOLDMAN:
Looking at the data from a different perspective, we see that 33% of patients had zero exacerbations, and 20% had one. Over the 4.5 years, 53% of patients had one or fewer exacerbations while on NUCALA. Results are descriptive.
ONSCREEN TEXT:
NUCALA (mepolizumab): Reduced Blood Eosinophil Levels and Maintained Within Normal‖‖‖ Levels
Mechanism of Action for NUCALA Has Not Been Definitively Established.
[Line graph showing approximately 80% reduction in blood eosinophil levels maintained over 4.5 years. Mean blood eosinophil levels were 240 cells/μL at baseline and approximately 40-50 on treatment. The geometric mean ratio to baseline values were 0.22 at Week 4 (n=330) and 0.13 at Week 228 (n=44) with other values falling within this range. There were fewer patients over the course of the study.]
4.5-Year Open-Label Study2,6
80% reduction in blood eosinophil levels maintained over 4.5 years
Results are descriptive. The clinical significance of these pharmacodynamic data is unknown.
‖‖‖Mean normal blood eosinophil levels in a general population of people without confounding factors were reported as 100 cells/μL (range: 34-257) and 107 cells/μL (5th, 95th percentile: 30,395); levels were varied based on age, sex, environmental exposures, and comorbid conditions.1,3
Graph reprinted from Khatri S, et al. J Allergy Clin Immunol. 2019;143(5):1742-1751,
Copyright 2019, with permission from Elsevier.
DR. GOLDMAN:
NUCALA reduced blood eosinophil levels and maintained them within normal levels. As shown here, there was an approximately 80% reduction in blood eosinophil levels maintained over 4.5 years. Mean blood eosinophil levels went from 240 cells per microliter at baseline to about 40 to 50 on treatment.
Results are descriptive, and the clinical significance of these pharmacodynamic data is unknown.
DR. GOLDMAN:
Now, please listen as the narrator presents additional Important Safety Information for NUCALA.
ONSCREEN TEXT:
IMPORTANT SAFETY INFORMATION (cont’d)
ADVERSE REACTIONS
The most common adverse reactions (≥5%) in patients receiving NUCALA (mepolizumab):
- Severe asthma trials: headache, injection site reaction, back pain, fatigue.
- CRSwNP trial: oropharyngeal pain and arthralgia.
- EGPA and HES trials (300 mg of NUCALA): no additional adverse reactions were identified to those reported in severe asthma clinical trials
Systemic reactions, including hypersensitivity, occurred in clinical trials in patients receiving NUCALA. Manifestations included rash, pruritus, headache, myalgia, flushing, urticaria, erythema, fatigue, hypertension, warm sensation in trunk and neck, cold extremities, dyspnea, stridor, angioedema, and multifocal skin reaction. A majority of systemic reactions were experienced the day of dosing.
Please see Important Safety Information for NUCALA throughout this video.
Please see full Prescribing Information and Patient Information for NUCALA at the adjacent links or visit NucalaHCP.com
NARRATOR:
Important Safety Information continued. ADVERSE REACTIONS: The most common adverse reactions, defined as greater than or equal to 5%, in patients receiving NUCALA in the severe asthma trials were headache, injection site reaction, back pain, fatigue. Those in the CRSwNP trial were oropharyngeal pain and arthralgia. In the EGPA and HES trials with 300 mg of NUCALA, no additional adverse reactions were identified to those reported in severe asthma clinical trials.
Systemic reactions, including hypersensitivity, occurred in clinical trials in patients receiving NUCALA. Manifestations included rash, pruritus, headache, myalgia, flushing, urticaria, erythema, fatigue, hypertension, warm sensation in trunk and neck, cold extremities, dyspnea, stridor, angioedema, and multifocal skin reaction. A majority of systemic reactions were experienced the day of dosing.
ONSCREEN TEXT:
IMPORTANT SAFETY INFORMATION (cont’d)
USE IN SPECIFIC POPULATIONS
The data on pregnancy exposures are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as mepolizumab, are transported across the placenta in a linear fashion as the pregnancy progresses; therefore, potential effects on a fetus are likely to be greater during the second and third trimesters.
Please see Important Safety Information for NUCALA throughout this video.
Please see full Prescribing Information and Patient Information for NUCALA at the adjacent links or visit NucalaHCP.com
NARRATOR:
USE IN SPECIFIC POPULATIONS:
The data on pregnancy exposures are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as mepolizumab, are transported across the placenta in a linear fashion as the pregnancy progresses; therefore, potential effects on a fetus are likely to be greater during the second and third trimesters.
Please see full Prescribing Information and Patient Information for NUCALA at the adjacent links or visit NucalaHCP.com.
ONSCREEN TEXT:
This program is sponsored by GSK. Thank you for your participation. Presentation intended for US healthcare providers only.
[GSK logo]
Trademarks are owned by or licensed to the GSK group of companies.
©2023 GSK or licensor.
MPLVID230002 April 2023
Produced in USA.
NARRATOR:
This program is sponsored by GSK. Thank you for your participation.
ONSCREEN TEXT:
Acronyms
ACQ-5=Asthma Control Questionnaire-5; AE=adverse event; AR=adverse reaction; BEC=blood eosinophil count; ED=emergency department; FEV=forced expiratory volume; ICS=inhaled corticosteroids; IV=intravenous; OCS=oral corticosteroids; OLE=open-label extension; Q4W=every 4 weeks; SAE=serious adverse event; SC=subcutaneous; SEA=severe eosinophilic asthma; SOC=standard of care.
ONSCREEN TEXT:
References
1. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198-1207.
2. Data on file, GSK.
3. Harrison, T. Canonica GW, Chupp G, et al. Real-world mepolizumab in the prospective severe asthma REALITI-A study: initial analysis. Eur Respir J. 2020;56(4);2000151.
4. Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371(13):1189-1197.
5. Lugogo N, Domingo C, Chanez P, et al. Long-term efficacy and safety of mepolizumab in patients with severe eosinophilic asthma: a multi-center, open-label, phase IIIb study. Clin Ther. 2016;38(9):2058-2070.
6. Khatri S, Moore W, Gibson PG, et al. Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2019;143(5):1742-1751.
7. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651-659.
ONSCREEN TEXT:
Chapter 2 Voiceover References:
1. Data on file, GSK.
2. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198-1207.
3. Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371(13):1189-1197.
4. Khatri S, Moore W, Gibson PG, et al. Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2019;143(5):1742-1751.
5. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651-659.
