FDA approves IL-5 Antagonist, Cinqair (reslizumab) to treat severe asthma.

March 23, 2016

The U.S. Food and Drug Administration approved Cinqair (reslizumab) for use with other asthma medicines for the maintenance treatment of severe asthma in patients aged 18 years and older. Cinqair is approved for patients who have a history of severe asthma attacks (exacerbations) despite receiving their current asthma medicines.

webmd_rm_photo_of_asthma_illustrationAsthma is a chronic disease that causes inflammation in the airways of the lungs. During an asthma attack, airways become narrow making it hard to breathe. Severe asthma attacks can lead to asthma-related hospitalizations because these attacks can be serious and even life-threatening. According to the Centers for Disease Control and Prevention, as of 2013, more than 22 million people in the U.S. have asthma, and there are more than 400,000 asthma-related hospitalizations each year.

DESCRIPTION

Reslizumab is a humanized interleukin-5 antagonist monoclonal antibody (IgG4κ). Reslizumab is produced by recombinant DNA technology in murine myeloma non-secreting 0 (NS0) cells. Reslizumab has a molecular weight of approximately 147 kDa.

CLINICAL PHARMACOLOGY

Mechanism of Action

  • Reslizumab is an interleukin-5 antagonist (IgG4, kappa).
  • IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils.
  • Reslizumab binds to IL-5 with a dissociation constant of 81 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil surface.
  • Inflammation is an important component in the pathogenesis of asthma.
  • Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation.
  • Reslizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils; however, the mechanism of reslizumab action in asthma has not been definitively established.

INDICATIONS AND USAGE

Reslizumab is indicated for the add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophilic phenotype.

Limitation of Use:

  • CINQAIR is not indicated for treatment of other eosinophilic conditions.
  • CINQAIR is not indicated for the relief of acute bronchospasm or status asthmaticus.

DOSAGE AND ADMINISTRATION

  • CINQAIR is for intravenous infusion only. Do not administer as an intravenous push or bolus
  • CINQAIR should be administered in a healthcare setting by a healthcare professional prepared to manage anaphylaxis
  • Recommended dosage regimen is 3 mg/kg once every 4 weeks by intravenous infusion over 20-50 minutes

DOSAGE FORMS AND STRENGTHS

Injection: 100 mg/10 mL (10 mg/mL) solution in single-use vials.

SAFETY & EFFICACY

  • The safety and efficacy of Cinqair were established in four double-blind, randomized, placebo‑controlled trials in patients with severe asthma on currently available therapies.
  • Cinqair or a placebo was administered to patients every four weeks as an add-on asthma treatment.
  • Compared with placebo, patients with severe asthma receiving Cinqair had fewer asthma attacks, and a longer time to the first attack.
  • In addition, treatment with Cinqair resulted in a significant improvement in lung function, as measured by the volume of air exhaled by patients in one second.

CONTRAINDICATIONS

Known hypersensitivity to reslizumab or any of its excipients

WARNINGS AND PRECAUTIONS

  • Anaphylaxis occurred with CINQAIR infusion in 0.3% of patients in placebo-controlled studies
  • Patients should be observed for an appropriate period of time after CINQAIR infusion; healthcare professionals should be prepared to manage anaphylaxis that can be life-threatening.
  • Discontinue CINQAIR immediately if the patient experiences anaphylaxis.
  • Acute Asthma Symptoms or Deteriorating Disease: CINQAIR should not be used to treat acute asthma symptoms or acute exacerbations.
  • Malignancy: Malignancies were observed in clinical studies.
  • Reduction in Corticosteroid Dosage: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with CINQAIR. Decrease corticosteroids gradually, if appropriate.
  • Parasitic (Helminth) Infection: Treat patients with pre-existing helminth infections before therapy with CINQAIR. If patients become infected while receiving CINQAIR and do not respond to anti-helminth treatment, discontinue CINQAIR until the parasitic infection resolves.

ADVERSE REACTIONS

The most common adverse reaction (incidence greater than or equal to 2%) includes oropharyngeal pain.

Cinqair is made by Teva Pharmaceuticals in Frazer, Pennsylvania.

References:

  1. FDA NEWS.
  2. Cinqair Prescribing Information
  3. Image Source: http://www.webmd.com/asthma/ss/slideshow-asthma-overview