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Chemocentryx Falls on Phase III Failure in Crohn's; Vercirnon Misses Endpoint

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By Jennifer Boggs
Managing Editor

Chemocentryx Inc. will have to await word from partner Glaxosmithkline plc on the future of vercirnon after the CCR9 antagonist missed its endpoint in the first of four Phase III studies in moderate to severe Crohn's disease.

Vercirnon, also known as Traficet-EN, marked the lead program from the companies' 2006 alliance and the most advanced oral small molecule to emerge from Chemocentryx's chemokine-targeting platform technology. Unsurprisingly, the news, which had not been expected until the fourth quarter, took a heavy toll on the biotech's stock, sending shares (NASDAQ:CCXI) falling 28.8 percent, or $3.37, to close at $8.32, with a range that was by far the lowest the stock has traded since Chemocentryx went public early last year.

Data from the 12-week, SHEILD-1 study, which enrolled 608 patients who were not adequately controlled with conventional therapy, including those who failed to respond to tumor necrosis factor-alpha antagonists, failed to hit the primary endpoint, defined as an improvement in clinical response vs. placebo as measured using the Crohn's Disease Activity Index. The study also missed the key secondary endpoint of showing clinical remission with the twice-daily vercirnon.

As a result, London-based GSK suspended new recruitment and dosing in the ongoing program while it intends to explore the data.

Chemocentryx's pipeline is based on a platform that uses the chemokine system to regulate the trafficking of immune cells, with the aim of offering a small-molecule approach to a host of autoimmune diseases currently treated with injectable biologics. By targeting the chemokine receptor CCR9, vercirnon is designed to stop T cells from migrating to the intestines and causing the inflammation that is characteristic of Crohn's disease.

Its safety profile, to date, had left analysts hopeful of success. In a May research report, Cowen and Co. analyst Eric Schmidt noted data from a Crohn's expert suggesting that vercirnon's "targeted inhibition of CCR9 offers a far better solution than current therapies, which have toxic side effects and rely on global immunosuppression."

Safety results from SHIELD-1 remained consistent, with adverse events similar among all treatment groups, including the placebo arm, with a trend in dose-dependent increases in overall adverse event rates.

Thomas J. Schall, president and CEO of Mountain View, Calif.-based Chemocentryx, acknowledged the firm was "clearly very disappointed" by the data from vercirnon, but said the news did not affect other pipeline programs, including its lead internal program, CCX140 in diabetic nephropathy, and other programs in the GSK alliance.

Originally inked in 2006, the GSK deal offered Chemocentryx the possibility of up to $1.5 billion in payments should all six programs covered in the collaboration be developed successfully. To date, three programs have been discontinued, though the alliance has provided sufficient funding for the biotech to date and supported it as it completed a $45 million initial public offering. (See BioWorld Today, Aug. 25, 2006, and Feb. 9, 2012.)

The vercirnon SHIELD program, which comprises four studies involving up to 2,500 patients with Crohn's disease, is being fully funded by GSK. The big pharma also exercised an option for CCX354, which targets the chemokine receptor CCR1, following a successful Phase II proof-of-concept trial in rheumatoid arthritis. By the end of this year, Chemocentryx anticipates a decision from GSK on CCX168, a C5aR inhibitor, in development for the treatment of ANCA-associated vasculitis.

On its own, the company is working on CCR2 inhibitor CCX140 and expects 12-week interim analysis data shortly in its Phase II trial in diabetic nephropathy.

As of June 30, it had $166.4 million on its balance sheet.