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NERLYNX is a small molecule that provides comprehensive, irreversible, intracellular pan-HER signaling inhibition3,20,30-35,*

NERLYNX PENETRATES THE BLOOD-BRAIN BARRIER

  •  In preclinical studies using an in vitro model, neratinib, a low-molecular-weight drug, demonstrated the ability to cross the blood-brain barrier
  •  In preclinical studies, neratinib inhibited key transporters associated with drug resistance in the brain
Mechanism of Action 36

Tumor growth prevention

  •  Intracellular binding of neratinib to the receptor tyrosine kinase signaling domain leads to sustained inhibition of HER2 signaling, inducing cell-cycle arrest and apoptosis3,30
  •  Neratinib inhibits downstream signaling, reducing tumor cell growth and proliferation and inducing tumor cell death in vitro30,32

*As seen in preclinical models.

EGFR: epidermal growth factor receptor; HER: human epidermal growth factor receptor; MAPK: mitogen-activated protein kinase.

Select IMPORTANT SAFETY INFORMATION

Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.

Lactation: Advise women not to breastfeed.

Please see additional IMPORTANT SAFETY INFORMATION below.

NERLYNX may inhibit HER2-ER crosstalk37

Adding NERLYNX to your anti-estrogen regimen may lead to more comprehensive anti-tumor activity37

Mechanism of Action

A HER2 ESCAPE MECHANISM

When ER is inhibited with endocrine therapy, crosstalk may cause upregulation of the HER2 pathway.37

Mechanism of Action 36

COMPREHENSIVE ANTI-TUMOR ACTIVITY

Adding NERLYNX to endocrine therapy may inhibit this key mechanism of resistance.37

ER: estrogen receptor; HER: human epidermal growth factor receptor.

Despite monoclonal antibody inhibition, resistance mechanisms allow tumors to proliferate37,38

In HER2+ breast cancer

Mechanism of Action

EGFR: epidermal growth factor receptor; HER: human epidermal growth factor receptor.

Resistance escape mechanisms can be grouped into 4 categories37-39

Truncation and masking
Mechanism of Action
Truncation and masking of the extracellular domain prevents binding of the monoclonal antibody to the HER2 receptor38
Lack of immune response
Mechanism of Action
Despite antibody binding and weakened signaling, the immune system is unable to engage and kill the tumor cell37-40
Crosstalk
Mechanism of Action
Increased HER signaling drives down ER-dependent gene expression; inhibiting HER signaling results in a compensatory increase in ER-dependent gene expression37,39,41-43
Upregulation
Mechanism of Action
Upregulation of HER2 downstream signaling pathways such as PI3K/AKT after loss of PTEN tumor suppression gene functioning can diminish HER2-targeted inhibition38

AKT: protein kinase B; ER: estrogen receptor; HER: human epidermal growth factor receptor; PI3K: phosphoinositide 3-kinase; PTEN: phosphatase and tensin homolog.

Addressing resistance mechanisms with a pan-HER, irreversible, intracellular blockade of pathways may help prevent tumor escape.30-32

IMPORTANT SAFETY INFORMATION

NERLYNX® (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated:

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

ADVERSE REACTIONS: The most common adverse reactions (reported in ≥5% of patients) were:

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS:

USE IN SPECIFIC POPULATIONS:

For Full Prescribing Information, please click here.