On April 1, 2019 Puma Biotechnology, Inc. (Nasdaq: PBYI) and Pierre Fabre reported that they have entered into an exclusive license agreement under which Pierre Fabre will develop and commercialize NERLYNX (neratinib) within Europe and part of Africa (Press release, Puma Biotechnology, APR 1, 2019, View Source [SID1234534843]). In September 2018 the European Commission granted marketing authorization for NERLYNX (neratinib) for the extended adjuvant treatment of adult patients with early stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who are less than one year from the completion of prior adjuvant trastuzumab-based therapy.

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Pierre Fabre will have exclusive commercialization rights for NERLYNX in European countries excluding Russia and Ukraine, along with countries in North Africa and francophone countries of West Africa. Pierre Fabre will also be responsible for conducting additional clinical studies and leading regulatory activities in connection with the European Medicines Agency (EMA).

Under the terms of the agreement, Puma will receive an upfront payment of $60 million, as well as additional regulatory and commercial milestone payments totaling up to $345 million. In addition, Puma will receive significant double-digit royalties on NERLYNX sales throughout the territory covered by the license agreement between Puma and Pierre Fabre.

"Puma is committed to providing access to NERLYNX to patients around the world and soon physicians and patients in Europe will have commercial availability of NERLYNX," stated Alan H. Auerbach, Chief Executive Officer and President of Puma. "Pierre Fabre has a robust commercial and medical oncology infrastructure that we hope will lead to rapid commercial access to NERLYNX."

"We are thrilled to provide this new therapy to patients with HER2-positive breast cancer throughout Europe," said Frederic Duchesne, Chief Executive Officer, Pierre Fabre Pharmaceuticals. "Pierre Fabre has developed a strong expertise and presence in breast cancer treatment and the addition of NERLYNX to our historical oncology portfolio will allow us to strengthen our commercial presence. We anticipate providing access to NERLYNX to patients throughout Europe in 2019 and 2020, starting with Germany."

About HER2-Positive Breast Cancer

Approximately 20% to 25% of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

Important EU NERLYNX (neratinib) Safety Information

All suspected adverse reactions should be reported in accordance with the national reporting system.

The adverse reactions described in this section were identified in the randomized Phase 3 clinical trial (n=2840). The most common adverse reactions of any grade were diarrhoea (93.6%), nausea (42.5%), fatigue (27.3%), vomiting (26.8%), abdominal pain (22.7%), rash (15.4%), decreased appetite (13.7%), abdominal pain upper (13.2%), stomatitis (11.2%), and muscle spasms (10.0%).

The most common Grade 3-4 adverse reactions were diarrhoea (Grade 3, 36.9% and Grade 4, 0.2%) and vomiting (Grade 3, 3.4% and Grade 4, 0.1%).

Adverse reactions reported as serious included diarrhoea (1.9%), vomiting (1.3%), dehydration (1.1%), nausea (0.5%), alanine aminotransferase increased (0.4%), aspartate aminotransferase increased (0.4%), abdominal pain (0.3%), fatigue (0.3%) and decreased appetite (0.2%).

For full European prescribing information, please refer to the NERLYNX (neratinib) Summary of Product Characteristics on the European Medicines Agency website (View Source).

Important Safety Information Regarding NERLYNX (neratinib) U.S. Indication

NERLYNX (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with HER2 overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade≥ 2 diarrhea that occurs after maximal dose reduction.
Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue NERLYNX inpatients experiencing Grade 4 liver abnormalities.
Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
ADVERSE REACTIONS: The most common adverse reactions (≥ 5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased and urinary tract infection.

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

DRUG INTERACTIONS:

Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors. When patients require gastric acid reducing agents, use an H2-receptor antagonist or antacid. Separate NERLYNX by at least 3 hours with antacids. Separate NERLYNX by at least 2 hours before or 10 hours after H2-receptor antagonists.
Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:

Lactation: Advise women not to breastfeed.