Puma's neratinib closing in on EU market
- The EMA has validated Puma Biotechnology’s application for its breast cancer drug, neratinib, as an extended adjuvant treatment of HER2-positive early stage breast cancer.
- Neratinib is an oral tyrosine kinase inhibitor that targets EGFR, HER2 and HER4 kinases.
- The data for the submission is from the ExteNET Phase 3 study, which showed a reduction of risk of invasive disease recurrence or death versus placebo at two years, at the expense of severe side effects.
The validation of the submission for approval of neratinib for early stage breast cancer in women previously treated with Herceptin (trastuzumab)-based adjuvant therapy is based on Puma Biotechnology’s ExteNET study, where treatment with neratinib resulted in a 2-year invasive disease-free survival rate for the neratinib of 93.9% compared with a 2-year disease-free survival rate for the placebo arm was 91.6%, a 33% reduction.
In a subgroup of patients with hormone receptor-positive disease, the reduction in the risk of invasive disease recurrence or death was 49% compared with placebo. However, this was associated with a 40% occurrence of severe diarrhea of grade 3 or higher.
These results mean that neratinib’s route towards the market has been less of a march and more of a long and winding road. In 2014, the company’s stock rose by more than 275% to $227 per share when the 33% increase in disease-free survival was announced.
However, this was followed by an almost equally dramatic slump in price. In late 2014 and following discussions with regulators, Puma changed the proposed indication from HER2-positive metastatic breast cancer to extended adjuvant HER2-positive early stage breast cancer, resulting in a fall in the stock price to $185. After the phase 3 data was presented at ASCO 2015, the negative reactions to the high levels of severe side effects resulted in a further stock fall of 9%.
The drug was licensed from Pfizer in 2011, granting Puma sole responsibility for global development and commercialization of neratinib, with milestone payments and royalties in the range of 10-20% going to Pfizer. The agreement was amended in 2014, with Pfizer no longer funding ongoing legacy clinical trials, in return for lower royalties, reduced to low- to mid-teens. This has pushed the risk towards Puma, and may signify reduced confidence in either Puma or the drug from Pfizer.
The company has also submitted a New Drug Applicaiton to the U.S. Food and Drug Administration, but has not yet announced whether or not it was accepted. Should the regulatory agency begin reviewing the filing, it could be approved in the U.S. by mid-2017. RBC Capital Markets analyst Simos Simeonidis said there is a 10%-15% chance that the FDA does not accept the NDA submission.
- Puma Biotechnology Statement
Follow Suzanne Elvidge on Twitter