Sanofi and Regeneron announced the FDA approval of their oncology drug Zaltrap (ziv-aflibercept). After the FDA granted it priority review, Zaltrap has been approved for use in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) for patients with metastatic colorectal cancer (mCRC) whose disease has progressed following prior treatment with Sanofi’s Eloxatine (oxaliplatin). The FDA approval was based on results from the 1226-patient Phase 3 VELOUR trial, which indicated that Zaltrap/FOLFIRI combination therapy increased the median overall survival of patients by 1.44 months compared to patients treated with a placebo and FOLFIRI (13.50 months versus 12.06, respectively). Additionally, the Zaltrap/FOLFIRI combination therapy improved the median progression-free survival to 6.9 months compared to 4.67 months in patients taking placebo/FOLFIRI. Sanofi also filed for marketing approval by the European Medicines Agency in Q4 2011; a decision is expected in late Q4 2012.
Also known as a Vascular Endothelial Growth Factor (VEGF) trap, Zaltrap inhibits tumor angiogenesis by acting as a soluble receptor that binds soluble VEGF-A and –B. This blocks these growth factors from binding and activating their respective VEGF receptors, inhibiting cell proliferation and the growth of new blood vessels. Zaltrap is a modification of Regeneron’s Eylea (aflibercept), which is currently marketed for the treatment of wet age-related macular degeneration (wet AMD). While both act as soluble VEGF traps, Zaltrap is specifically targeted towards VEGF mutations frequently found in cancers.
The approval of Zaltrap is a major milestone for Regeneron, as this will be the company’s first attempt at marketing an oncology drug. However, Sanofi is an established player not only in oncology, but specifically CRC, the indication for which it already markets Eloxatine. Sanofi has the experience and marketing muscle that will lead to a successful launch and maximize Zaltrap sales.
Sanofi undoubtedly hopes that Zaltrap sales will help offset the revenue lost following the expiry of Eloxatine’s US market exclusivity in August 2012. US sales accounted for €806m of Eloxatine’s €1.1 billion total sales in 2011. However, it is unlikely that Zaltrap will reach the blockbuster status of Eloxatine. The 1.44-month increase in median overall survival data compared to FOLFIRI is unimpressive, even among oncology drugs for which 3- and 4-month increases in median overall survival are hailed as major milestones in disease treatment. An increase in overall survival of less than two months may not be enough to convince patients to risk the severe adverse events associated with Zaltrap use, especially when there are other options to choose from. The drug carries a black box warning of severe and potentially fatal hemorrhage and gastrointestinal perforation, as well as compromised wound healing. There is currently a shortage of leucovorin, one of the components of the FOLFIRI regimen, in the US, which will also hinder sales.
As a brand, Zaltrap will have a difficult time competing with Roche/Genentech’s Avastin (bevacizumab) and Bristol-Myers Squibb/Eli Lilly’s Erbitux (cetuximab), two drugs approved for the same indication. Both drugs have expanded their oncology market share by receiving approval for multiple indications; Erbitux is approved for patients with various stages of head and neck cancer as well as mCRC, and Avastin is approved for glioblastoma, metastatic kidney cancer, advanced nonsquamous non-small cell lung cancer and metastatic colorectal cancer. While Sanofi and Regeneron have attempted to employ this strategy in the development of Zaltrap, Zaltrap has failed trials in prostate cancer, lung cancer and pancreatic cancer. Consequently, it is unlikely that the Zaltrap brand will benefit from extensions into other indications.
Oncologists and patients will surely be grateful to have another option in the mCRC treatment arsenal. However, with so many barriers and competition from multiple drugs approved for the same patient population, it is unlikely that Zaltrap will be the blockbuster Sanofi and Regeneron are hoping for. GlobalData estimates that Zaltrap sales will generate less than $250m in 2013.
Date: August 7, 2012
Filed Under: Drug Discovery