Puma Biotech (PBYI) on Tuesday evening announced a significant, unexpected delay in its timeline for filing a New Drug Application with the FDA for lead drug product, neratinib. Neratinib is an inhibitor of HER2 that many on Wall St. expect will dominate the “extended” adjuvant breast cancer market, used in the year after post-surgical (adjuvant) treatment with Roche-Genentech’s (RHHBY) Herceptin (trastuzumab). The delay also creates new headwinds for PBYI in 2016.
PBYI fell 15% in after hours trading on Tuesday.
Puma indicated that it would not be filing a New Drug Application for Neratinib until the first quarter of 2016, pushed back from previous guidance for a filing in the first half of 2015. In recent meetings with the FDA, the regulatory body said that Puma will need to submit data from preclinical carcinogenicity studies, which Puma has yet to complete, prior to submitting the NDA. the previous assumptionw as that carcinogenicity data could be submitted after approval; management said this new animal data should be available in November of 2015.
Besides the delay’s affect on modeling future neratinib cash flows, a second headwind for PBYI has emerged: completion of Roche-Genentech’s APHINITY trial, testing Herceptin with another HER2 inhibitor, Perjeta (pertuzumab), to determine if the combination is better than Herceptin alone in the adjuvant setting. That data is expected sometime in 2016, likely during the FDA’s review of neratinib.
APHINITY is a 4,800-patient phase III trial comparing the efficacy and safety of docetaxel, Herceptin, and placebo against docetaxel, Herceptin and Perjeta as adjuvant therapy in patients with HER2+ breast cancer. Pertuzumab, like Herceptin and neratinib, targets HER2, though through a different part of the molecule. If Perjeta in combination with Herceptin demonstrates a disease-free survival benefit similar to that seen in the phase III ExteNET trial of neratinib, providers may prefer the former, particularly considering Perjeta’s improved toxicity profile and the potential for one year of treatment with Herceptin/Perjeta, vs a second year with Neratinib.
Guidance is for APHINITY to read out in 2016, prior to or during the FDA’s review of Neratinib in adjuvant breast cancer. That’s a profound risk for the stock, and could set the latter part of this decade up for an arduous head-to-head commercial battle between Roche and the smaller Puma.
Worth noting, results from PBYI’s recent NEfERTT study, indicate that neratinib does not improve on Herceptin in the adjuvant setting, though it seems the drug may have a benefit in breast cancer patients with brain metastases.
