Assistant Managing Editor

Shares of Regeneron slid 14 percent after data showed that anti-angiogenic cancer drug candidate aflibercept missed its endpoint in a Phase II trial in advanced ovarian cancer patients.

While the data were not a total surprise - Regeneron and partner Sanofi-Aventis reported interim results at last year's ASCO meeting - it was "hard not to be disappointed by the response rates," wrote analyst Michael Aberman, of Credit Suisse Securities LLC.

Interim data had showed an overall 8 percent response rate, as reported by trial investigators, but final data, analyzed by an independent review committee (IRC), reported a 4.6 percent response rate for patients receiving 4 mg/kg of fusion protein aflibercept and a 0.9 percent response rate for those in the 2 mg/kg arm.

Data were determined using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. A response rate of greater than 5 percent was needed for the study to meet its primary endpoint.

Comparing aflibercept's data to those of blockbuster cancer drug Avastin (bevacizumab, Genentech Inc.), a monoclonal antibody that also works by targeting vascular endothelial growth factor (VEGF) to inhibit angiogenesis, is "particularly discouraging," Aberman added in a research note.

Data from Avastin trials in ovarian cancer demonstrated response rates as high as 28 percent (in a National Cancer Institute-sponsored study in recurrent ovarian cancer patients), but Aberman cautioned that the Avastin data were reported by investigator analyses instead of the "more stringent" IRC response criteria.

Investigator analyses of the aflibercept data showed a response rate of 7.3 percent for the 4 mg/kg dose arm and 3.6 percent for the 2 mg/kg arm, though that was still lower than expected, even in light of the interim data presented last year.

The news sent Regeneron's stock (NASDAQ:REGN) down $2.89, or 13.5 percent, Wednesday to close at $18.58, but the Tarrytown, N.Y.-based firm said the data did show some encouraging trends.

"We looked at levels of CA-125, the protein signature elevated in ovarian cancer," said Robert Terifay, senior vice president of commercial at Regeneron, and response rates, defined as at least a 50 percent reduction in CA-125 protein levels, were 11.6 percent in the 4-mg/kg group and 11.5 percent in the 2-mg/kg group.

"When we looked at the patients who had CA-125 [reductions] and those with the traditional RECIST responses, we ended up with an overall 13.8 percent response rate," he told BioWorld Today. "So we feel there is clear activity" of aflibercept in ovarian cancer, though both Regeneron and Sanofi intend to evaluate the dataset further before determining the next steps in that indication.

Terifay added that the Phase II miss in ovarian cancer will not affect or delay aflibercept's ongoing development in other oncology indications.

The drug is in four Phase III trials: in second-line metastatic colorectal cancer in combination with folinic acid, 5-FU and irinotecan; in first-line metastatic pancreatic cancer in combination with gemcitabine; in first-line metastatic androgen-independent prostate cancer in combination with docetaxel and prednisone; and in second-line metastatic non-small-cell lung cancer in combination with docetaxel.

The NSCLC trial could be completed as early as November 2009, while the colorectal cancer and pancreatic cancer studies have estimated completion dates in 2010. The prostate cancer study is projected to finish up in mid-2012.

At the upcoming American Society of Clinical Oncology meeting in Chicago, Regeneron and Sanofi are expected to report additional aflibercept data, including Phase II results of the drug in symptomatic malignant ascites showing that eight of 10 evaluable patients achieved a repeat paracentesis response rate, as well as data from a 48-patient NCI-sponsored study showing a response in 50 percent of patients with anaplastic glioma and 30 percent of patients with glioblastoma.

Regeneron and Sanofi have been working together on aflibercept, formerly known as the VEGF Trap program, since 2003.

The companies recently expanded their collaborative efforts with a potential $1 billion cash and stock deal, signed in November, to discover, develop and commercialize antibodies.

Terms of that agreement called for Sanofi to increase its ownership of Regeneron to about 19 percent by purchasing $312 million of the company's stock.

In return, Regeneron gave Paris-based Sanofi access to its VelociSuite technologies. (See BioWorld Today, Nov. 30, 2007.)

Elsewhere in its pipeline, Regeneron is working on a late-stage ophthalmic program, VEGF Trap-Eye, with partner Bayer Healthcare.

That product is in two 1,200-patient Phase III studies in age-related macular degeneration. Phase II data reported at the recent Association for Vision and Ophthalmology meeting showed that, on average, patients on an as-needed dosing schedule maintained the gain visual acuity and decrease in retinal thickness achieved at week 12 through week 32 of the study.

Regeneron, which reported a net loss of $11.6 million, or 15 cents per share, for the first quarter, had about $827.9 million in the bank as of March 31.