Marketing Authorization Approval in Japan for TAVNEOS® Capsules 10mg, a selective Complement C5a Receptor Antagonist

Kissei Pharmaceutical Co., Ltd. (Head Office: Matsumoto, Nagano; Chairman and CEO: Mutsuo Kanzawa, "Kissei") announced that it has received marketing authorization approval in Japan for the selective complement C5a receptor inhibitor, TAVNEOS^® Cap.10mg (general name: avacopan) for the treatment of granulomatosis with polyangitis (GPA) and microscopic polyangiitis (MPA), the two main types of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

TAVNEOS^® is the first-in-class oral-administered agent presenting the treatment effect to MPA and GPA by selectively blocking the complement C5a receptor. Kissei has gained the exclusive license to develop and commercialize Avacopan in Japan from Vifor Fresenius Medical Care Renal Pharma Ltd. (Headquarters: Switzerland, CEO: Alfredo Merino, "VFMCRP") in June 2017. Then, Kissei joined the global phase-III clinical trial (ADVOCATE trial) together with VFMCRP, which was sponsored by the originator, ChemoCentryx, Inc, (Headquarters: the U.S., CEO: Thomas J. Schall). TAVNEOS^® has been granted orphan-drug designation by the Ministry of Health, Labor and Welfare in March 2019. Based on the successful results of the pivotal phase III ADVOCATE study, Kissei has submitted marketing authorization application for the indication of MPA and GPA in February 2021. Outside Japan, NDA in the US and MAA in EU have been filed by ChemoCentryx and VFMCRP respectively and they are under review. The approval of TAVNEOS^® in Japan is the first marketing authorization worldwide.

The goal of the treatment for MPA and GPA is induction of remission and sustaining remission and it's said that early suppression of inflammation and prevention or mitigation of relapse which causes organ damage and increase mortality risk are important in terms of improvement of long-term outcomes. The combination of high-dose glucocorticoid and immunosuppressant for induction of remission and the combination of low-dose glucocorticoid and immunosuppressant for sustaining remission are recommended as standard-of-care, however, the risk of severe side effects by glucocorticoid and immunosuppressant has been recognized as an issue. Based on the results of ADVOCATE trial, it's expected that TAVNEOS^® will be a new-treatment-option which leads to reduction in dose and the usage period of glucocorticoid and suppression of relapse.

Mutsuo Kanzawa, CEO of Kissei, said "We have strived to develop new treatment drug for intractable diseases and orphan diseases for which no sufficient treatment is available. It is delightful for us to receive the first marketing authorization approval in the world, and we again highly commit ourselves to focus on helping the patients suffering from MPA and GPA so that they can live a calm and healthy life."
"We are delighted that TAVNEOS^® has been approved in Japan, the first market worldwide, and congratulate our partner Kissei for this significant milestone," said Abbas Hussain, CEO of Vifor Pharma Group. "ANCA-associated vasculitis is officially designated an intractable disease in Japan, indicating a rare disease without any effective treatment but for which long-term treatment is required. We are confident that Kissei will fully focus on bringing this breakthrough treatment to this patient population, helping them lead better, healthier lives."

Kissei has established Rare Disease Project in April 2021 in order to accurately and adequately provide information on ANCA associated vasculitis and TAVNEOS^®. Kissei strives to further contribute to the treatment of MPA and GPA through distribution of TAVNEOS^® and promotion of its proper use.

A milestone payment is triggered by the approval. It, however, has already been incorporated into the consolidated earnings forecast for the fiscal year ending March 2022 announced in May 2021.


《Reference》

Product Summary of TAVNEOS® Capsules 10mg
Brand Name:
TAVNEOS® Capsules 10mg

General Name:
Avacopan

Indications:
Microscopic polyangiitis and Granulomatosis with polyangiitis

Dosage and Administration:
The usual oral dosage for adults is 30mg of avacopan twice daily after breakfast and supper

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 TAVNEOS® Capsules 10mg (general name: avacopan)
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. MPA and GPA classified as AAV which are the indication of avacopan, are rare and severe autoimmune diseases that are 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 agent in all countries outside the United States. VFMCRP has granted Kissei a sub-license for the agent in Japan.

About ADVOCATE trial
This is a global double-blind controlled phase-III trial in 331 patients with MPA and GPA in 18 countries and regions, 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 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 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 (marketed 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.