Data confirm FASENRA’s well-established safety profile consistent with previous Phase III trials
At least 75% of FASENRA-treated patients with elevated blood eosinophil levels had zero exacerbations each year of the open-label period
WILMINGTON, Del., May 19, 2021 – Results from a new integrated analysis including data from the MELTEMI Phase III open-label extension trial showed FASENRA® (benralizumab) was well-tolerated for up to five years, with a long-term safety profile consistent with previous Phase III trials in adult patients with severe asthma.
Results were presented today at the American Thoracic Society (ATS) 2021 International Conference.
During the period of the BORA and MELTEMI extension trials, adverse events (AEs) and serious adverse events (SAEs) did not increase from rates comparable to placebo observed in the Phase III pivotal trials. Rates of serious infection, hypersensitivity, immunogenicity, and malignancy were low across all treatment groups, with no deaths during the on-treatment window. The most commonly reported AEs during the open-label period for patients receiving FASENRA every eight weeks were nasopharyngitis, asthma, headache, and bronchitis. These data confirm FASENRA’s well-established safety profile.
In secondary endpoints, FASENRA sustained the reduction in asthma exacerbation rates observed during predecessor SIROCCO, CALIMA, ZONDA and BORA Phase III trials with annualized asthma exacerbation rates (AAER) remaining consistently low over the five-year treatment period.
In patients taking high-dosage inhaled corticosteroids (ICS) with blood eosinophil levels of greater than or equal to 300 cells per microliter who received FASENRA every eight weeks, AAER decreased from 3.1 exacerbation/year pre-treatment to 0.5 in the predecessor studies with a further reduction to 0.2 by year four of the open-label trial. In the same treatment group 59% of patients experienced zero exacerbations during the four years of the open-label period (BORA and MELTEMI) and at least 75% of patients each year experienced zero exacerbations. In the final year of the trial 87% of patients experienced zero exacerbations.
Arnaud Bourdin, Head of Pulmonology, Professor of Respiratory Medicine at Arnaud de Villeneuve Hospital, Montpellier, France and primary investigator for MELTEMI, said: “Clinicians treating severe eosinophilic asthma want to ensure the therapy they prescribe will continue to help patients control their illness in the long term, with a consistent safety profile. Based on the new MELTEMI data, physicians and their patients should feel confident that FASENRA provides a treatment option that can do exactly that – reduce exacerbations, with a known safety profile.”
Mark White, Global Franchise Head, FASENRA, said: “The new data from MELTEMI are exciting as they confirm FASENRA’s efficacy and safety profile seen in previously reported Phase III trials. These results should offer further confidence to physicians and patients that the positive outcomes they’re experiencing whilst using FASENRA can be maintained for the longer-term.”
FASENRA is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries and is approved for self-administration in the US and EU. The Food and Drug Administration (FDA) granted Orphan Drug Designation for FASENRA for eosinophilic granulomatosis with polyangiitis (EGPA) (November 2018), hypereosinophilic syndrome (HES) (February 2019) and eosinophilic oesophagitis (EoE) (August 2019).
IMPORTANT SAFETY INFORMATION
Known hypersensitivity to benralizumab or excipients.
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. These reactions generally occur within hours of administration, but in some instances have a delayed onset (ie, days). Discontinue in the event of a hypersensitivity reaction.
Acute Asthma Symptoms or Deteriorating Disease
FASENRA should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.
Reduction of Corticosteroid Dosage
Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. 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.
Parasitic (Helminth) Infection
It is unknown if FASENRA will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with FASENRA. If patients become infected while receiving FASENRA and do not respond to anti-helminth treatment, discontinue FASENRA until infection resolves.
FASENRA is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype.
- FASENRA is not indicated for treatment of other eosinophilic conditions
- FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus
The most common adverse reactions (incidence ≥ 5%) include headache and pharyngitis.
Injection site reactions (eg, pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treated with placebo.
USE IN SPECIFIC POPULATIONS
The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.
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Asthma is a heterogeneous disease affecting an estimated 339 million people worldwide. Approximately 10% of asthma patients have severe asthma. Despite the use of inhaled asthma controller medicine, currently available biologic therapies and oral corticosteroids (OCS), many severe asthma patients remain uncontrolled. Due to the complexity of severe asthma, many patients have unclear or multiple drivers of inflammation and may not qualify for or respond well to a current biologic medicine.
Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced health-related quality of life. Patients with severe asthma are at an increased risk of mortality and have twice the risk asthma-related hospitalizations. There is also a significant socio-economic burden, with these patients accounting for over 50% of asthma-related costs.
MELTEMI is a multicenter, open-label safety extension, Phase III trial to assess the safety and tolerability of FASENRA administered subcutaneously in severe, uncontrolled asthma patients on ICS and long-acting beta2-agonists therapy with or without chronic OCS and/or other asthma controllers. Participants had completed one of three Phase III placebo-controlled predecessor trials (SIROCCO, CALIMA, ZONDA), then enrolled in the double-blind BORA safety extension trial, further transitioning into the MELTEMI open-label extension trial.
The integrated analysis results include patients who had received FASENRA for up to five years from the beginning of the treatment period in the predecessor studies. A total of 446 patients were included in the analysis. Of these, 384 (86.1%) completed the on treatment period and 16% were on treatment for greater than or equal to five years. Mean on treatment duration was equal to or greater than three years in each group. As typically observed in longer-term trials, due to the duration of time participants were followed, fewer patients continued through to the later stages of the study than completed the predecessor trials.
The primary endpoint in MELTEMI was FASENRA safety and tolerability, which was measured by rates of AEs and SAEs during the on-treatment period. The secondary endpoints included a subset of primary and secondary endpoints from the Phase III predecessor studies: annual asthma exacerbations, in-patient hospitalization, and/or an emergency department visit, absolute blood eosinophil counts over the course of the on-treatment period; and immunogenicity.
FASENRA (benralizumab) is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of blood and tissue eosinophils in most patients via apoptosis (programmed cell death).
FASENRA is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries, and is approved for self-administration in the US, EU and other countries.
FASENRA is in development for other eosinophilic diseases and chronic obstructive pulmonary disease. The US Food and Drug Administration granted Orphan Drug Designation for FASENRA for EGPA (November 2018), HES (February 2019) and EoE (August 2019).
FASENRA was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd., Japan.
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US - 53643 Last Updated 5/2021