Hoping to introduce the first marketed product for a group of rare chronic inflammatory conditions, Regeneron Pharmaceuticals Inc. completed a rolling biologics license application for its interleukin-1 (IL-1) Trap.

That BLA is the first to emerge from the company's Trap program, which also includes two partnered VEGF Trap candidates targeting cancer and wet age-related macular degeneration.

Assuming the product gets a priority review by the FDA, as requested, the IL-1 Trap could gain approval within six months for cryopyrin-associated periodic syndrome (CAPS).

The agency previously granted fast-track and orphan drug status for that indication, which refers to inherited conditions, such as familial cold autoinflammatory syndrome and Mucke-Wells syndrome, and are characterized by spontaneous systemic inflammation.

A very rare disease - there are no concrete figures, but estimates put the number of U.S. patients ranging from "a few hundred to a few thousand" - CAPS results when the secretion of interleukin-1 is "deranged due to a genetic mechanism," said George Yancopoulos, executive vice president and chief scientific officer of Regeneron.

Patients with CAPS have mutations of the CIAS1 gene, which encodes the protein cryopryin to induce IL-1 secretion. Regeneron's IL-1 Trap (rilonacept) is designed to inhibit IL-1 by attaching to and neutralizing it in the blood stream before it can attach to cell-surface receptors and trigger disease activity in body tissue.

"We found that this one Trap essentially turned this disease off," Yancopoulos told BioWorld Today. "The effect was literally [like a] light switch."

Data included in the BLA includes results from two Phase III studies. In the first study, a six-week trial designated Part A, patients randomized to receive IL-1 Trap had an 85 percent reduction in their mean symptom scores vs. 13 percent in the placebo group, as measured by a composite symptom score composed of daily evaluations of fever/chills, rash, fatigue, joint pain and eye redness/pain.

The second study, Part B, involved the same patients re-randomized to either switch to placebo or continue IL-1 treatment for a nine-week treatment period, and results from that trial showed that patients switched to placebo had a five-fold increase in their mean symptom score, compared to those remaining on IL-1 Trap.

Those "incredibly positive studies" and resulting BLA also represent a significant milestone for Regeneron, Yancopoulos said.

Not only do they "validate the whole Trap concept" that the company has been working on from the early discovery stages of the role cell-surface receptors play in disease, but it also clears a path for exploratory studies in other indications with the specific IL-1 Trap. Regeneron is "now laying the groundwork to test more broadly in inflammatory diseases," such as gout and other indications.

Shares of Regeneron (NASDAQ:REGN) gained 42 cents Friday to close at $18.64.

While it awaits word from the FDA on the status of IL-1 Trap, the Tarrytown, N.Y.-based company, along with partner Bayer Healthcare AG, of Leverkusen, Germany, is gearing up to start a Phase III program of VEGF Trap-Eye in wet AMD during the third quarter.

That product targets the vascular endothelial growth factor (VEGF), the same target as South San Francisco-based Genentech Inc.'s much-touted Lucentis (ranibizumab), which recorded sales of $211 million in the first quarter.

Beyond wet AMD, Regeneron and Bayer also are exploring the use of VEGF Trap-Eye in diabetic eye diseases and other eye diseases and disorders. Under the collaboration terms, the companies would commercialize the product jointly outside the U.S., while Regeneron maintains exclusive U.S. rights.

The company also would go up against Genentech again with its VEGF Trap candidate for cancer, which would compete with Genentech's blockbuster VEGF inhibitor, Avastin (bevacizumab), though some investors remain skeptical in light of data released last week during the American Society of Clinical Oncology meeting in Chicago.

Regeneron and partner Sanofi-Aventis Group, of Paris, reported preliminary results from a 153-patient Phase II study showing that VEGF Trap shrank tumors in 8 percent of patients with chemotherapy-resistant ovarian cancer, but analysts estimated that a reduction of at least 10 percent might be needed to impress the FDA. Data from that same study showed that the drug stopped tumors from growing in 71 percent of patients and that its use results in low rates of bowel perforation.

Regeneron and Sanofi are investigating VEGF Trap in several solid tumor types, including colorectal, non-small-cell lung, prostate, pancreatic and gastric. Sanofi has said it intends to file a first registration submission to regulatory agencies as early as 2008.

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