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Apr 28, 2014
 |  BioCentury  |  Product Development

Not so negative

Why Puma still sees role for neratinib in HER2-negative breast cancer

Even though data presented this month show neratinib failed to graduate from I-SPY 2 in HER2-negative breast cancer, Puma Biotechnology Inc. thinks the compound will have a role in the setting.

According to the company, part of the reason neratinib didn't clear the hurdle is that treatment was stopped in all neratinib arms after the compound graduated in a different population: HER2-positive/hormone receptor-negative neoadjuvant breast cancer.

I-SPY 2 is an adaptive Phase II study run by the Biomarkers Consortium. The open-label trial is testing unapproved drugs in biomarker-defined subgroups of patients with neoadjuvant breast cancer. To graduate, a compound must demonstrate an 85% probability of success in Phase III.

Another reason may have been a suboptimal dosing regimen, as investigators shied away from using higher doses of neratinib due to high rates of diarrhea.

Since the HER2-negative population is three times larger than the HER2-positive population, investors lopped $770 million off Puma's market cap over April 7 and 8, following the presentation. Puma closed that week down $30.24 (28%) to $76.17, with a market cap of $2.3 billion.

Puma says it has optimized the dosing to ameliorate the side effect, and intends to continue developing neratinib in the HER2-negative setting.

The company is also continuing development in the HER2-positive/HR-negative setting, where at least one doctor says the bar for improvement over SOC is high.

The case for negative

Neratinib is a small molecule inhibitor of EGFR1 (HER1), HER2 and HER4 kinases that Puma licensed from Pfizer Inc. in 2011.

I-SPY 2 tested neratinib in 10 population segments within neoadjuvant breast cancer based on combinations of HER2 mutation and hormone receptor status, and MammaPrint score. The MammaPrint test is a 70-gene signature chip marketed by Agendia B.V. to assess the risk of breast cancer recurrence.

HER2-positive patients received standard chemotherapy plus either neratinib or Herceptin trastuzumab, and HER2-negative patients received standard chemotherapy with...

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