Nerlynx (neratinib) for the Treatment of Breast Cancer, United States of America


Tyrosine kinase inhibitor

Nerlynx™ (neratinib) is a tyrosine kinase inhibitor indicated for the treatment of adult patients with early-stage HER2-overexpressed or amplified breast cancer.

The drug was developed by US-based company Puma Biotech, which received US Food and Drug Administration (FDA) approval for Nerlynx™ following adjuvant trastuzumab-based therapy in July 2017. The company plans to launch the drug commercially in the US market in September 2017.

The marketing authorisation application (MAA) for Nerlynx™ in Europe is currently under review by the European Medicines Agency (EMA).

HER2-positive breast cancer causes and symptoms

Breast cancer symptoms include a lump in the breast, a change in shape, dimpling of the skin, fluid coming from the nipple, or a red scaly patch of skin.

HER2-positive breast cancer constitutes between 20% and 25% of all types of breast cancer cases. It is more aggressive than other types and spreads faster.

More than 3.1 million breast cancer survivors are estimated to be present in the US.

Nerlynx's mechanism of action

Nerlynx™ contains a tyrosine kinase inhibitor (TKI) that binds to Epidermal Growth Factor Receptor 2 (HER2) and HER 4. The drug reduces downstream growth, promoting signal transduction pathways and HER2 expressing carcinoma cell lines.

The drug is available in the form of 240mg tablets for oral administration.

Clinical trials on Nerlynx

Puma Biotechnology enrolled patients for a Phase III clinical trial known as NALA on Nerlynx™ in July 2017. The study enrolled 600 patients with third-line HER2-positive metastatic breast cancer. The patients were randomised to receive PB272 plus Xeloda or Tykerb plus Xeloda. The trial is being conducted in North America, Europe, and the Asia-Pacific.

The co-primary endpoints of the study include progression free survival (PFS) and overall survival (OS). The primary analysis of PFS from the study is expected to be available by the first half of 2018.

FDA approval for Nerlynx™ was based on results obtained from a Phase III clinical trial known as ExteNET trial, which was a multi-centre, randomised, double-blind, placebo-controlled study. It enrolled 2,840 women with early-stage HER2-positive breast cancer, who had two years of completing adjuvant trastuzumab. The patients were randomised to receive either Nerlynx™ or placebo for one year.

Results of the study demonstrated that the patients treated with Nerlynx™ showed invasive disease-free survival (iDFS) of 94.2% compared to iDFS of 91.9% in placebo group after two years of follow-up.

The most common adverse reactions found in the patients treated with Nerlynx™ were diarrhoea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms, as well as dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. The most common adverse reaction that led to the discontinuation of the clinical trial was diarrhoea.

Marketing commentary on Puma Biotechnology

Puma Biotechnology is a biopharmaceutical company focused on in-licensing innovative drug candidates for cancer care and developing them further for commercialisation. Most of the company's drug candidates are under development for the treatment of HER2-positive breast cancer.

The medicines currently available in the market for the treatment of HER2 positive breast cancers include Kadcyla developed by Genentech and Tykerb developed by GlaxoSmithKline.