Submission of New Drug Application for Avacopan (CCX168), a Complement C5a Receptor Inhibitor, in Japan

Kissei Pharmaceutical Co., Ltd. (Head Office: Matsumoto, Nagano; Chairman and CEO: Mutsuo Kanzawa, "Kissei") announced that it has submitted a new drug application for approval of manufacturing and marketing in Japan for the complement C5a inhibitor, avacopan (generic name, development number: CCX168), as a treatment for microscopic polyangiitis and granulomatosis with polyangiitis classified as anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA-associated vasculitis or ANCA vasculitis).

If approved, avacopan would be the first-in-class orally administered selective complement 5a receptor inhibitor exerting an anti-inflammatory effect, for the treatment of patients with ANCA-associated vasculitis. In June 2017, Kissei obtained the exclusive right to develop and market avacopan in Japan from Vifor Fresenius Medical Care Renal Pharma (Headquarter: Switzerland; CEO: Alfredo Merino; "VFMCRP"). Subsequently, Kissei participated with VFMCRP in the global double-blind phase-III clinical trial (ADVOCATE trial), which was sponsored by the originator, ChemoCentryx, Inc.,(Headquarter: the U.S., CEO: Thomas J. Schall). This application for regulatory approval is based on positive results from the pivotal ADVOCATE trial of avacopan.

In overseas, avacopan is currently under review for regulatory approval in the U.S. and the European Union for the treatment of patients with ANCA-associated vasculitis. In March 2019, the Ministry of Health, Labour and Welfare has granted avacopan orphan-drug designation for microscopic polyangiitis and granulomatosis with polyangiitis.

Kissei strives to contribute to patients suffering from intractable diseases by bringing avacopan smoothly into the clinical setting, by establishing an organizational structure to provide appropriate information on ANCA-associated vasculitis and avacopan.

The milestone payment is trigerred by this event, but it has already been incorporated into the consolidated earnings forecast for the fiscal year ending March 2021 announced on November 5, 2020.

《Reference》

About ADVOCATE trial:
This is a global double-blind controlled phase-III trial in 331 patients with ANCA-associated vasculitis in 20 countries, including Japan. In this trial, the avacopan treatment group has demonstrated non-inferiority to the steroid group in remission of vasculitic symptoms at Week 26 and superiority to the steroid group in sustained remission at Week 52 as assessed by the primary endpoint of Birmingham Vasculitis Activity Score (BVAS). The avacopan group also showed better tolerability compared to the steroid group.
The study result was published in the February 18, 2021 issue of New England Journal of Medicine*.

* David R.W. Jayne, M.D., Peter A. Merkel, M.D., M.P.H., Thomas J. Schall, Ph.D., and Pirow Bekker, M.D, Ph.D. for the ADVOCATE Study Group. Avacopan for the Treatment of ANCA-Associated Vasculitis
The New England Journal of Medicine, 2021, 384（7）, 599　 https://www.nejm.org/doi/full/10.1056/NEJMoa2023386

About ANCA (anti-neutrophil cytoplasmic auto-antibody)-associated vasculitis (AAV):
AAV is a rare and severe autoimmune disease characterized by no or very little immune complex deposition, necrotizing inflammation of the small blood vessels, and high ANCA-positive rates. It damages various organs, including the kidneys, lungs, and nervous system. The number of patients with AAV is estimated to be over 10,000 in Japan (based on the number of recipients of the certificates for special disease treatment for the designated intractable disease as of the end of fiscal 2018). The current standard of care centered on glucocorticoids in AAV treatment show efficacy, but there are issues such as high frequency of adverse events that pose a clinical problem*.

* The New England Journal of Medicine, 2021, 384（7）, 664

About Complement C5a receptor:
Complement is a system of proteins found in blood and is involved in various immune responses and preventing infection. There are many kinds of complements, generally expressed as C by taking the initial letter of complement. Of these, C5a acts as a chemotactic factor, attracting neutrophils to the inflamed area. Avacopan is thought to exhibit anti-inflammatory properties by inhibiting the C5a receptor, thereby suppressing excessive activity of neutrophils that damage blood vessels.

About Avacopan (CCX168):
Avacopan, an orally-administered small-molecule agent for the treatment of rare kidney diseases, has been developed by ChemoCentryx. It inhibits C5a receptors in leukocytes, including neutrophils, and exhibits anti-inflammatory properties by preventing the migration of leukocytes as well as the expression and induction of adhesion molecules. ANCA-associated vasculitis, which is one of the targets of avacopan, is a rare and severe autoimmune disease that is designated as an intractable disease by the Ministry of Health, Labour, and Welfare in Japan. The number of patients with ANCA-associated vasculitis has been increasing rapidly in recent years, and in many cases, they present necrotizing glomerulonephritis. As results of ADVOCATE trials, avacopan treatment for AAV is expected to demonstrate efficacy and reduce the risk of adverse events in the current standard of care.
ChemoCentryx has granted VFMCRP a license for the agentin all countries outside the United States. VFMCRP has granted Kissei a sub-license for the agent in Japan.

About Vifor Fresenius Medical Care Renal Pharma (VFMCRP):
VFMCRP belongs to the Vifor Pharma Group and is a joint venture of Vifor Pharma Group and Fresenius Medical Care, developing and commercializing innovative and high quality therapies to improve the life of patients suffering from chronic kidney disease (CKD) worldwide. VFMCRP has also granted Kissei the license for sucroferric oxyhydroxide (sold as Velphoro® in Europe), P-TOL® in Japan, for the treatment of hyperphosphatemia. Vifor Pharma Group is a global pharmaceuticals company. It aims to become the global leader in iron deficiency, nephrology and cardio-renal therapies. Vifor Pharma Group is headquartered in Switzerland, and listed on the Swiss Stock Exchange (SIX Swiss Exchange, VIFN, ISIN: CH0364749348).

About ChemoCentryx, Inc.:
ChemoCentryx is a biopharmaceutical company developing new oral medications targeted at inflammatory and autoimmune diseases and cancer, which is headquarted in the US and is listed on NASDAQ (NASDAQ: CCXI). Avacopan is the agent discovered by ChemoCentryx.