SHIELD 4 Efficacy Results in Line With Positive Results in PROTECT-1, an Earlier Phase II Clinical Trial in Crohn's Disease
Data Featured at the 79th Annual Scientific Meeting of the American College of Gastroenterology (ACG)
MOUNTAIN VIEW, Calif., Oct. 20, 2014 (GLOBE NEWSWIRE) -- ChemoCentryx, Inc., (Nasdaq:CCXI), a clinical-stage biopharmaceutical company focused on autoimmune diseases, inflammatory disorders and cancer, today reported data from the Phase III SHIELD 4 clinical trial in Crohn's disease with vercirnon, an inhibitor of the chemokine receptor known as CCR9. Data showed that patients experienced improved response and remission rates when taking a higher dose of vercirnon (500 mg twice daily (BID) vs. 500 mg once daily (QD)). There was no evidence of higher gastrointestinal, hepatic, or cardiovascular adverse events with the twice daily group compared to the once daily group.
Data were presented at the 79th American College of Gastroenterology (ACG) Annual Scientific Meeting being held in Philadelphia, Pa. from October 17-22.
"These SHIELD 4 data are consistent with our earlier positive PROTECT-1 study data," said Thomas J. Schall, Ph.D., President and Chief Executive Officer, ChemoCentryx. "As with PROTECT-1, the data indicate that vercirnon is safe and well tolerated in patients with Crohn's disease, and there is a dose-dependent improvement in symptoms in the observed patient population in SHIELD 4. The Phase III drug CCX282/vercirnon, in addition to our second-generation, Phase II-ready CCR9 inhibitor, CCX507, provide a strong complement of drugs in our CCR9 program for which we intend to find a strategic partner."
SHIELD 4 Study Design and Results
The SHIELD 4 trial, a randomized, double-blind induction study in patients with moderate-to-severe Crohn's disease, was designed to treat patients with one of two dose regimens of vercirnon and then enroll the clinical responders in a Phase III maintenance clinical trial (SHIELD 2). The SHIELD development program, including the SHIELD 4 trial, was conducted by ChemoCentryx's then-partner, GlaxoSmithKline (GSK), who had earlier licensed vercirnon for development.
Two hundred fifty-three patients were enrolled in SHIELD 4, 118 of whom completed the clinical trial prior to the early termination of the study by GlaxoSmithKline in September 2013. The primary endpoint of the trial was the proportion of patients with a Crohn's disease activity index (CDAI) ≥ 100-point response (100-point decrease in CDAI score) at week 12. The secondary endpoint was the proportion of patients in clinical remission (CDAI < 150) at week 12. Adult patients with a baseline CDAI of 220 to 450, C-reactive protein (CRP) ≥ 3 mg/L or fecal calprotectin > 200 μg/g were randomized to receive either 500 mg QD or 500 mg BID vercirnon for 12 weeks. Baseline CDAI was 323 (± 56) with a range of 220-450.
Regarding response data, in SHIELD 4, in the observed population, i.e. those who completed the trial prior to the premature study termination (n=118), the CDAI ≥ 100-point response at week 12 was 56 and 69 percent in the 500 mg QD and in the 500 mg BID groups, respectively. This compares to the PROTECT-1 study where the CDAI ≥ 100-point response at week 12 was 55 percent in the 500 mg QD group (there was no 500 mg BID group in PROTECT-1). This is in contrast to the earlier reported SHIELD 1 induction study where the CDAI ≥ 100-point response at week 12 was 28 and 27 percent in the 500 mg QD and 500 mg BID groups, respectively.
Regarding remission data, in SHIELD 4, in the same observed population, remission (defined as CDAI < 150) at week 12 was 26 and 36 percent in the 500 mg QD and in the 500 mg BID groups, respectively. This compares favorably to the Phase II PROTECT-1 study where remission at week 12 was 30 percent in the 500 mg QD group.
The increase in response and remission rates with the higher dose of vercirnon in SHIELD 4 is in contrast to the lack of dose response observed in the SHIELD 1 trial. The response observed in the population of patients who completed 12 week dosing in SHIELD 4 was similar to the positive results from the Phase IIB PROTECT-1 trial.
There were no safety issues observed in the SHIELD 4 trial, and unlike in SHIELD 1, gastrointestinal adverse events were not higher in the 500 mg BID group than the 500 mg QD group. In SHIELD 4, there were no cardiac safety or liver toxicity signals.
|Observed Population||Intent-to-Treat Population*|
| Time |
| Vercirnon 500 |
| Vercirnon 500 |
| Vercirnon 500 |
| Vercirnon 500 |
|* Intent-to-Treat Population includes patients who were still ongoing in the trial, but not allowed to complete the 12 week treatment regimen, at the time the study was prematurely terminated by GSK. Accordingly, no 12 week data were available for these patients for the purposes of primary endpoint determination.|
ACG Poster # P1049 October 20, 2014 from 10:30 am to 4:00 pm ET
"SHIELD 4 Phase 3 Clinical Trial With Orally Administered CCR9 Inhibitor Vercirnon in Crohn's Disease"
Vercirnon (CCX282-B) is a small molecule, orally administered compound in capsule form and which is believed to modify the inappropriate immune system response underlying inflammatory bowel disease (IBD) by blocking the chemokine receptor known as CCR9. In adults, CCR9 is a highly specific receptor expressed by inflammatory T cells that migrate to the digestive tract. The migration of inflammatory cells to the small and large intestine is believed to cause the persistent inflammation seen in Crohn's disease and ulcerative colitis -- the two principal forms of IBD.
ChemoCentryx, Inc. is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing orally-administered therapeutics that target the chemokine and chemoattractant systems in order to treat autoimmune diseases, inflammatory disorders and cancer. The chemokine system is a biological network that regulates inflammation via a collection of secreted chemokine molecules, or ligands, and their specific cell surface receptors. Based on its proprietary drug discovery and drug development platform, ChemoCentryx has generated multiple clinical and preclinical-stage programs, each targeting distinct chemokine and chemoattractant receptors with different small molecule compounds. CCX140, a CCR2 inhibitor, has been shown to be safe and well tolerated while demonstrating clinical activity on glycemic indices in a Phase II clinical trial in type 2 diabetics, and is now in Phase II clinical development for the treatment of diabetic nephropathy. CCX168, a C5aR inhibitor, is in Phase II development for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). CCX168 appears to be safe, well tolerated and successful in allowing both reduction and elimination of high-dose corticosteroids, part of standard of care for AAV patients, without compromising efficacy or safety during a 12-week treatment period. Vercirnon (also known as Traficet-EN or CCX282) is a specific CCR9 inhibitor for the treatment of inflammatory bowel disease. Other clinical programs include CCX872, a next generation CCR2 inhibitor currently in Phase I clinical development, CCX507, a next generation CCR9 inhibitor, which has successfully completed Phase I development and CCX354, a CCR1 inhibitor which successfully completed a Phase II clinical trial for the treatment of rheumatoid arthritis. ChemoCentryx also has several programs in advanced preclinical development.
ChemoCentryx cautions that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as "may," "could," "will," "would," "should," "expect," "plan," "anticipate," "believe," "estimate," "intend," "predict," "seek," "contemplate," "potential" or "continue" or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. These statements include the Company's statements regarding the potential clinical efficacy of vercirnon and its intention to find a strategic partner for the CCR9 program. The inclusion of forward-looking statements should not be regarded as a representation by ChemoCentryx that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risks and uncertainties inherent in the ChemoCentryx business and other risks described in the Company's filings with the Securities and Exchange Commission ("SEC"). Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and ChemoCentryx undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included under the heading "Risk Factors" in ChemoCentryx's periodic reports filed with the SEC, including ChemoCentryx's Annual Report on Form 10-K for the year ended December 31, 2013 which is available from the SEC's website (www.sec.gov) under the heading "Investors." All forward-looking statements are qualified in their entirety by this cautionary statement. This cautionary statement is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
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