Nerlynx Granted FDA’s Orphan Drug Status for Treating Breast Cancer with Brain Metastases

The U.S. Food and Drug Administration (FDA) has granted orphan drug status to Puma Biotechnology’s Nerlynx (neratinib) for the treatment of HER2-positive breast cancer in women with brain metastases.

Between 10 to 15% of people with metastatic breast cancer develop brain metastases. However, that number reaches up to 30% in women with advanced HER2-positive breast cancer.

Orphan drug designation provides Puma with benefits, including financial incentives for therapy development and commercialization. It also provides U.S. market exclusivity for a period of seven years following the medication’s approval, FDA support for clinical studies, and special fee exemptions and reductions.

The designation is given to investigative treatments aimed at helping people with a rare disease, which means it affects fewer than 200,000 people in the U.S.

“Receiving Orphan Drug Designation from the FDA signifies our continued progress and commitment to developing treatments for patients with HER2-positive breast cancer,” Alan H. Auerbach, chairman, CEO, and president of Puma, said in a press release.

Nerlynx was approved by the FDA in July 2017 as an extended, adjuvant therapy — an added treatment to lower the risk that the cancer will come back — for adults with early-stage HER2-positive breast cancer. The treatment was designed to follow adjuvant therapy with trastuzumab (brand names Herceptin, and others).

The active substance, neratinib, is a small molecule that works as an irreversible tyrosine kinase inhibitor (TKI), blocking the epidermal growth factor receptor HER2, as well as other receptors. It is designed to inhibit HER2 — overexpressed by some breast tumors and associated with a more aggressive disease — to prevent cancer cell proliferation and induce its death.

Nerlynx is able to cross the blood-brain barrier — a highly selective membrane that shields the central nervous system (CNS, brain and spinal cord) from large molecules and invaders in circulation. That suggests it can bring therapeutic benefits to patients whose HER2-positive breast cancer has spread to the brain.

In a prior Phase 2 trial (NCT01494662), a combination of Nerlynx and the chemotherapy capecitabine (brand name Xeloda, by Genentech, generics also available) effectively shrank brain metastasis in nearly half of HER2-positive breast cancer participants — with tolerable toxicity.

This led the National Comprehensive Cancer Network (NCCN) to include the combination as a recommended treatment option in its clinical practice guidelines for breast cancer patients with brain metastases. However, the combination is still investigational and has not been approved by the FDA.

“Despite expanded treatment options for HER2-positive breast cancer, brain metastases in these patients represent a significant clinical challenge, as well as sources of morbidity and mortality for most of these patients. The blood-tumor penetrability of Nerlynx represents a potential treatment option for these underserved patients,” Auerbach said.

Puma also is seeking to extend the use of Nerlynx in combination with capecitabine to treat women with HER2-positive breast cancer whose disease has spread to other parts of the body, and have failed at least two other treatments targeting the HER2 protein.