Eosinophils & MOA | NUCALA (mepolizumab) for HCPs

How NUCALA works to target eosinophils

NUCALA targets interleukin-5 (IL-5)

IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils.

On this page:

NUCALA mechanism of action (MOA)

Role of eosinophils in health and severe asthma

Eosinophil reduction with NUCALA

How NUCALA works

The MOA of mepolizumab in asthma has not been definitively established.

View the NUCALA MOA

This video illustrates the MOA for mepolizumab in asthma.

Role of eosinophils in health and in severe asthma

Role of eosinophils in maintaining health includes¹:

Regulating the immune system
Tissue regeneration and repair
Host protection (eg, defending against parasitic infection)

Too many airway tissue eosinophils in patients with severe asthma is associated with^2,3:

Increased symptoms
Greater likelihood for exacerbations
Airway inflammation

NUCALA reduced blood eosinophil levels and maintained within normal levels

4.5-year open-label study^4,5

Blood eosinophil reduction over 4.5 years graph

Mean blood eosinophil levels⁵: 240 cells/µL at baseline; ~40-50 cells/µL on treatment.

Results are descriptive. The clinical significance of these pharmacodynamics data is unknown.

Note: Mean normal blood eosinophil levels in a general population of subjects without confounding factors have been reported as 100 cells/µL (range: 34-257) and 107 cells/µL (5^th, 95^th percentile: 30, 395); levels vary based on age, sex, environmental exposures, and comorbid conditions.^6,7

See 4.5-year open-label study design and primary endpoint (safety)

Next: Blood eosinophil unit conversion calculator

Learn about NUCALA exacerbation data

Who is the NUCALA patient?

Indication

Important Safety Information

Indication & Important Safety Info

NUCALA is indicated for the add-on maintenance treatment of patients 6 years and older with severe asthma with an eosinophilic phenotype. NUCALA is not indicated for the relief of acute bronchospasm or status asthmaticus.

CONTRAINDICATIONS
NUCALA should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.

Important Safety Information

CONTRAINDICATIONS
NUCALA should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.

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). If a hypersensitivity reaction occurs, discontinue NUCALA.

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
In controlled clinical trials, 2 serious adverse reactions of herpes zoster occurred with NUCALA compared to none with placebo. Consider vaccination if medically appropriate.

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.

ADVERSE REACTIONS
In clinical trials in patients receiving NUCALA, the most common adverse reactions (≥5%) were headache, injection site reaction, back pain, and fatigue. Systemic reactions (allergic and nonallergic), including hypersensitivity, also occurred. Manifestations included rash, pruritus, headache, myalgia, and flushing; the majority were experienced the day of dosing.

USE IN SPECIFIC POPULATIONS
A pregnancy exposure registry monitors pregnancy outcomes in women exposed to NUCALA during pregnancy. To enroll call 1-877-311-8972 or visit www.mothertobaby.org/asthma.

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.

MPTWCNT200079 January 2021.

REFERENCES

Weller PF, Spencer LA. Functions of tissue-resident eosinophils. Nat Rev Immunol. 2017;17(12):746-760.
Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med. 2005;172(2):149-160.
Malinovschi A, Fonseca JA, Jacinto T, Alving K, Janson C. Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects. J Allergy Clin Immunol. 2013;132(4):821-827 e5.
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.e7.
Data on file, GSK.
Felarca AB, Lowell FC. The total eosinophil count in a nonatopic population. J Allergy. 1967;40(1):16-20.
Hartl S, Breyer MK, Burghuber A, et al. Blood eosinophil count in the general population: typical values and potential confounders. [published online ahead of print, February 14, 2020]. Eur Respir J. doi:10.1183/13993003.01874-2019.

To report SUSPECTED ADVERSE REACTIONS, contact GSK at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Trademarks are owned by or licensed to the GSK group of companies.

This is my caption