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August 1, 2012 6:24 pm

Regeneron’s Zaltrap expected to gain FDA approval in second-line mCRC

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This article is provided to FT.com readers by BioPharm Insight—a news service focused on providing insight into the most price sensitive issues in the global pharmaceutical market. www.biopharminsight.com

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Regeneron (NASDAQ:REGN) and Sanofi’s (NYSE:SNY) Zaltrap (aflibercept) is likely to gain marketing approval in the US for metastatic colorectal cancer (mCRC) as a second-line treatment, experts told BioPharm Insight.

The US Food and Drug Administration (FDA) is expected to make a decision on August 4. The FDA will decide on use of aflibercept in combination with FOLFIRI, a standard chemotherapy regimen, in second-line use, or in patients who have failed prior treatment.

In 2012, more than 143,000 people in the US will be diagnosed with colorectal cancer and about 51,690 patients will die from the disease, according to the National Cancer Institute (NCI). It is the fourth most common cancer in both men and women, according to NCI data.

mCRC treatment involves successive rounds of chemotherapy with adjuvant therapies. Roche (VTX:ROG)/Genentech’s Avastin (bevacizumab) is the most commonly used adjuvant therapy and is approved for first-line use.

Aflibercept will get second-line approval with the FOLFIRI chemotherapy regimen, said Dr Tanios Bekaii-Saab, associate professor, College of Medicine, The Ohio State University. Data from the pivotal 1226-patient Phase III VELOUR, which compared aflibercept against placebo in the second-line setting, is convincing, added Dr Ki Chung, medical oncologist, Cancer Center of the Carolinas, South Carolina.

This places aflibercept behind Avastin, though, since it is approved for first-line use, noted Bekaii-Saab. With no data to show superiority over Avastin, Regeneron’s strategy could be to initiate a price battle, he added.

Regeneron declined to comment.

A study presented earlier this year at the annual meeting of the American Society of Clinical Oncology known as the TML study looked at using Avastin back-to-back from the first-line into the second-line setting. The positive results with Avastin could be difficult for aflibercept to overcome in the second-line setting, Bekaii-Saab added.

Additionally, the VELOUR trial showed aflibercept had a slightly higher-toxicity profile than Avastin, said Dr Sherif Raouf, a clinical oncology consultant at Barking, Havering and Redbridge University Hospitals, Essex, UK. Severe or life-threatening grade 3 or 4 adverse events that occurred with a more than 2% greater incidence with aflibercept than with placebo included infections, hypertension, neutropenia and proteinuria, according to a company press release.

The most serious side effects associated with Avastin, according to the drug’s label, are gastrointestinal perforation, surgery and wound healing complications as well as serious bleeding. The label also includes other side effects like hypertension, proteinuria and arterial thromboembolic events.

Aflibercept and Avastin both target VEGF signaling, which prevents blood vessels from growing and nourishing cancerous growths. Aflibercept looks like a more potent inhibitor of VEGF than Avastin, said Dr Craig Lockhart, an oncologist and associate professor, Washington University School of Medicine in St. Louis. He agreed, though, aflibercept probably has worse toxicity.

Because there is no head-to-head data to directly compare the drugs, it’s unclear that aflibercept has greater toxicity than Avastin, countered Dr John Strickler, an oncologist at the Duke Cancer Institute in North Carolina. Thus, both strategies - continuing with Avastin or changing to aflibercept in the second-line setting - have benefit, he said.

That’s why the role of payers could be big, Strickler added.

Multiple options and the possibility of a pricing battle benefits patients and doctors, said Bekaii-Saab. A report from Cowen, an equity research firm, estimates Avastin achieved about USD 2bn-2.5bn in first-line mCRC sales in 2010. Regeneron’s potential new drug Zaltrap could achieve USD 275m in US sales in this setting by 2016, according to the same report.

Since 2009, aflibercept has failed Phase III trials in first-line metastatic pancreatic cancer, second-line non-small cell lung cancer and first-line metastatic androgen-independent prostate cancer. In January, BioPharm Insight reported aflibercept is not expected to demonstrate a significant benefit as a first-line treatment for mCRC after Phase II study results in this setting were presented, according to oncologists.

Regeneron is currently partnered with Sanofi over global co-promotion rights for Zaltrap, except in Japan.

Sanofi submitted aflibercept for European Medicines Agency approval in previously treated mCRC patients in December 2011, according to an SEC filing.

Regeneron’s current market cap is USD 11.53bn.

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