ChemoCentryx Announces Positive Top-Line Results for CCX168 from the Phase II ANCA-Associated Vasculitis CLASSIC Study and Advances Plans to Initiate Phase III Development
-- Safety study objective achieved: CCX168 shown to be well tolerated in patients with ANCA-associated vasculitis when added to current standard of care regimen –
-- Initiation of Phase III development program with CCX168 in ANCA-associated vasculitis planned by the end of 2016 --
MOUNTAIN VIEW, Calif., June 16, 2016 (GLOBE NEWSWIRE) -- ChemoCentryx, Inc., (Nasdaq: CCXI) today announced positive top-line results from its Phase II CLASSIC (CLinical ANCA Vasculitis Safety Study of Inhibitor of C5aR) study with CCX168 in patients with anti-neutrophil cytoplasmic auto-antibody (ANCA)-associated vasculitis, or AAV.
CCX168 is an orally-administered small molecule that is a selective inhibitor of the complement C5a receptor, or C5aR, and is the lead drug candidate in the Company's orphan and rare disease program.
CCX168 has been granted orphan drug designation for AAV in the US and EU and was also granted access to the European Medicines Agency’s (EMA) PRIority MEdicines (PRIME) initiative, which supports accelerated assessment of investigational therapies addressing unmet medical need. The goal of the CCX168 development program in AAV is to reduce or eliminate the use of chronic high dose glucocorticosteroids (steroids) in the current standard of care (SOC) treatment. However, in order to inform potential regulatory queries and eventual labeling requirements for CCX168 in AAV, the Phase II CLASSIC study was designed to assess the safety profile of CCX168 when added to the current SOC.
“These results from the Phase II CLASSIC trial are consistent with the safety and efficacy data observed in the Phase II CLEAR trial, which was designed to assess whether high-dose glucocorticoids used in the standard of care regimen for the treatment of ANCA-associated vasculitis could potentially be replaced with CCX168,” said Dr. Peter A. Merkel, Chief of Rheumatology and Professor of Medicine at the University of Pennsylvania. “ANCA-associated vasculitis is a life- and organ-threatening disease with multiple clinical manifestations. While current treatment options have improved outcomes for patients with this complex disease, substantial unmet needs still exist. In particular, treatments that could achieve more rapid disease control and prevent permanent organ damage, or allow for reduction of total administered doses of glucocorticoids and thus reduce treatment-related toxicities (a so-called “steroid-sparing effect”), would be great advances for patients with this disease.”
“We are very pleased with the successful completion of the CCX168 CLASSIC safety study, which we believe to be the last step in our Phase II development for CCX168 in AAV. Despite best practice today, premature mortality within a year of AAV diagnosis is unacceptably high, and the steroid-containing standard therapy is a principle driver. Use of steroids is also known to lead to psychiatric problems, diabetes, muscle wasting, bone fractures, weight gain, and increased risk of infections.” said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. “In preparation for End-of-Phase II meetings with European and U.S. regulatory authorities, we are now proceeding to include CLASSIC data in our upcoming regulatory discussions as we look towards the initiation of Phase III development by the end of this year. CCX168 reflects our unwavering commitment to AAV patients: to develop safer and more effective treatment for this rare disease.”
Phase II CLASSIC Study Design and Top Line Results
Whereas a previous Phase II study of CCX168, the CLEAR study, was focused on efficacy outcomes, the CLASSIC study was intended to confirm that CCX168, were it for whatever reason to be administered in addition to the current SOC, would not engender additional safety issues in AAV patients. The CLASSIC study was performed as a double-blind, placebo-controlled trial, in which 42 subjects with newly diagnosed or relapsed AAV all received the current SOC (which includes chronic high dose steroids in combination with rituximab or cyclophosphamide), and were also randomized into three cohorts:
- SOC plus placebo (SOC alone);
- SOC plus 10 mg CCX168 twice daily (SOC+10 mg CCX168); and
- SOC plus 30 mg CCX168 twice daily (SOC+30 mg CCX168).
The CLASSIC safety study met its objectives. The addition of CCX168 to current SOC therapy did not add safety concerns beyond those seen with SOC alone. The incidence of serious adverse events (SAEs), was similar across treatment groups in the study:
- SAEs = 2 of 13 (SOC alone); 2 of 13 (SOC + 10 mg CCX168); 3 of 16 (SOC + 30 mg CCX168);
- All 7 of the SAEs have been observed with drugs used as part of the current SOC regimen; and
- As expected, steroid-associated infections comprised 4 of 7 of the SAEs.
While the CLASSIC safety study was not designed or powered for inferential statistical analyses on efficacy endpoints (since it is important to note that the development goal for CCX168 is to reduce or eliminate chronic high dose steroids from the AAV SOC), treatment response for each cohort was assessed at week 12 using the Birmingham Vasculitis Activity Score (BVAS). Baseline BVAS scores were well balanced between the three treatment groups in the trial, with mean scores ranging from 15.1 to 15.9.
|SOC alone||SOC+10 mg CCX168||SOC+30 mg CCX168|
|BVAS response* at week 12||10/13||11/12||12/15|
(BVAS responders / BVAS ITT**)
- *BVAS response was prospectively defined as a decrease from baseline of at least 50% in BVAS plus no worsening in any body system
- ** BVAS ITT prospectively defined as all patients with at least one post-baseline, on-treatment BVAS score
- (Note: All definitions above are consistent with those in previous CLEAR Phase II study)
Rapid BVAS improvement was also assessed:
|SOC alone||SOC+10 mg CCX168||SOC+30 mg CCX168|
|BVAS = 0 at week 4||2/13||1/12||5/15|
The Company expects to report further details from the CLASSIC safety study at upcoming medical meetings.
The results of the Phase II CLASSIC safety study of CCX168 in AAV add to the data obtained from the previously reported Phase II CLEAR efficacy study. CLEAR assessed whether CCX168 (30 mg twice daily) could replace high dose chronic steroids in the current SOC regimen in AAV. The CLEAR efficacy study successfully met its primary and secondary endpoints, demonstrating that CCX168 -- in the absence of chronic high dose steroids -- induced rapid clinical benefits in AAV as measured by improvements in BVAS, renal function parameters, and patient reported outcomes.
About ANCA-Associated Vasculitis
Anti-neutrophil cytoplasmic auto-antibody (ANCA)-associated vasculitis, or AAV, is a type of rare autoimmune inflammation caused by auto-antibodies. AAV encompasses granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis), microscopic polyangiitis (MPA), eosinophilic polyangiitis (formerly Churg-Strauss syndrome) and renal limited vasculitis.
AAV represents a severe and often fatal autoimmune disease that is characterized by inflammation that can destroy different organ systems. AAV is the lead indication in the Company's orphan and rare disease program which has the objective of eliminating chronic high dose steroids, which are associated with significant safety issues including death, from the standard of care (SOC) regimen in AAV and replace steroids with CCX168.
AAV affects approximately 40,000 people in the U.S. (with approximately 4,000 new cases each year) and greater than 75,000 people in Europe (with at least 7,500 new cases each year), and is currently treated with courses of immunosuppressants (cyclophosphamide or rituximab) combined with high dose steroid administration. Following initial treatment, up to 30 percent of patients relapse within six to 18 months, and approximately half of all patients will relapse within three to five years.
Current SOC for AAV is associated with significant safety issues. First year mortality is approximately 11 to 18 percent. The single major cause of premature mortality is not disease-related adverse events, but rather infection that is thought largely to be a consequence of steroid administration. Indeed, the multiple adverse effects of courses of steroid treatment (both initial courses and those that are repeated as a consequence of relapse) are major causes of both short-term and long-term disease and death. Such therapy related adverse events contribute significantly to patient care costs, as well as to the diminution of quality of life for patients.
By damaging the body's small blood vessels, AAV affects many organ systems, mostly the kidneys, eyes, lungs, sinuses and nerves. This damage is caused by the destructive activity of inflammatory leukocytes in the body, with neutrophils considered to be the terminal effector cell. In AAV, neutrophils are attracted to sites of vascular destruction as well as activated at those sites by the activity of the complement system product known as C5a and its receptor, C5aR, which is the target of CCX168. By blocking the C5aR, CCX168 is thought to reduce vasculitis by reducing neutrophil activation, accumulation, and adhesion, as well as vascular permeability.
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. CCX168, a C5aR inhibitor, is in Phase II development for the treatment of anti-neutrophil cytoplasmic auto-antibody-associated vasculitis (AAV). CCX168 appears to be safe, well tolerated and successful in allowing reduction and elimination of high-dose steroids, part of standard of care for AAV patients, without compromising efficacy or safety in clinical studies to date. CCX168 is also in Phase II studies for the treatment of atypical hemolytic uremic syndrome (aHUS) and immunoglobulin A nephropathy, or IgA nephropathy (IgAN). ChemoCentryx has licensed exclusive rights to Vifor Pharma to commercialize CCX168 in Europe and certain other markets outside of the U.S. and most of Asia. CCX872, a CCR2 inhibitor, successfully completed Phase I development and is in development for the treatment of non-resectable pancreatic cancer. CCX140, a distinct CCR2 inhibitor, successfully completed a Phase II clinical trial where it was shown to be safe and well tolerated while demonstrating statistically significant improvement in albuminuria in patients with diabetic nephropathy. Other clinical programs include CCX507, a next generation CCR9 inhibitor, which has successfully completed Phase I development, vercirnon (also known as Traficet-EN or CCX282) a specific CCR9 inhibitor for the treatment of inflammatory bowel disease, 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," "continue" or "project" 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 timing of initiating Phase III development in AAV for CCX168 and whether CCX168 will be shown to be effective in Phase III clinical trials in the treatment of AAV and other orphan and rare diseases. 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 filed with the SEC March 14, 2016 and its other reports which are available from the SEC's website (www.sec.gov) and on ChemoCentryx's website (www.chemocentryx.com) under the heading "Investors." All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
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