Astex Pharmaceuticals, Taiho Oncology, and Otsuka Pharmaceutical announce FDA and Health Canada approval of INQOVI (decitabine and cedazuridine tablets)

Astex Pharmaceuticals, Taiho Oncology, and Otsuka Pharmaceutical announce FDA and Health Canada approval of INQOVI® (decitabine and cedazuridine) tablets, oral hypomethylating agent (HMA) therapy for intermediate and high-risk MDS and CMML

INQOVI is the first orally administered hypomethylating agent approved by the FDA and Health Canada
INQOVI is a fixed-dose combination of the hypomethylating agent decitabine and the cytidine deaminase inhibitor cedazuridine, which prevents degradation of decitabine in the gastrointestinal tract and liver and enables its absorption via oral dosing
Approval is based on the ASCERTAIN phase 3 and other supporting studies that compared systemic exposure to decitabine from oral INQOVI with exposure from IV decitabine and assessed safety and efficacy of INQOVI
INQOVI delivers an option for intermediate and high-risk MDS and CMML patients to potentially reduce the number of office visits and to take their medication from the convenience and comfort of their homes
Pleasanton, CA, Princeton, NJ, and Tokyo, Japan, July 7, 2020. Astex Pharmaceuticals, Inc.; Taiho Oncology, Inc.; and Otsuka Pharmaceutical Co., Ltd. today announce that the U.S. Food and Drug Administration (FDA) and Health Canada have approved INQOVI® (decitabine and cedazuridine) tablets. The three companies are all part of the Otsuka group of companies.

INQOVI is the first and only orally administered hypomethylating agent for the treatment for adults with intermediate and high-risk myelodysplastic syndromes (MDS) including chronic myelomonocytic leukemia (CMML),1 two blood malignancies.

Approval was based on data from the ASCERTAIN phase 3 study and supporting phase 1 and 2 clinical studies.  The ASCERTAIN phase 3 study evaluated the five-day, decitabine exposure equivalence between oral INQOVI and intravenous decitabine. The safety and efficacy of INQOVI was also assessed in the clinical studies.

The review and approval of INQOVI was conducted under the ORBIS initiative from the FDA Oncology Center of Excellence (OCE) with simultaneous submission and regulatory review in the U.S., Canada, and Australia. The FDA also reviewed the NDA under Priority Review status. INQOVI is not currently approved in Australia. INQOVI was formerly named ASTX727, its experimental compound code.

“Intravenous or subcutaneous administered hypomethylating agents have been the cornerstone for the treatment of patients with MDS and CMML since the mid-2000s,” said Guillermo Garcia-Manero, MD, Professor and Chief of Section of Myelodysplastic Syndromes, Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, Texas, and Principal Investigator of the ASCERTAIN clinical study. “The FDA’s approval of INQOVI builds on the proven therapeutic utility of hypomethylating agents in these diseases and offers a new orally administered option that offers patients an alternative to five consecutive days of IV infusions every month during a treatment period that can extend to several months.”

“Until now, patients with intermediate and high-risk MDS and CMML have not had an approved, orally administered hypomethylating agent option for treatment of their disease,” said Mohammad Azab, MD, president and chief medical officer of Astex Pharmaceuticals, Inc. “The INQOVI clinical program was designed to deliver an oral alternative to IV decitabine based on comparative decitabine exposure data in the clinical trials, and to assess INQOVI’s safety and efficacy profile. As part of the ORBIS project initiative of FDA and Health Canada we were able to share and address information requests simultaneously with both agencies resulting in a more efficient review and completion of assessment in a timely manner. The outcome is expedited availability of this important oral alternative to patients in both countries” added Dr. Azab. “We greatly appreciate the FDA’s priority review and Health Canada’s review of the INQOVI NDA / NDS under Project ORBIS and the approval of a new therapeutic option for patients with these diseases.”

INQOVI is an orally administered, fixed-dose combination of the approved anti-cancer DNA hypomethylating agent, decitabine, together with cedazuridine,2 an inhibitor of cytidine deaminase.3 By inhibiting cytidine deaminase in the gut and the liver, INQOVI is designed to allow for oral delivery of decitabine over five days in a given cycle to achieve comparable systemic exposure to IV decitabine (geometric mean ratio of the 5-day cumulative decitabine area-under-the-curve following 5 consecutive once daily doses of INQOVI compared to that of intravenous decitabine was 99% (90% CI: 93, 106).1 The phase 1 and phase 2 clinical study results have been published in Lancet Haematology4 and Blood,5 respectively. The phase 3 ASCERTAIN study data was presented at the American Society of Hematology (ASH) Meeting in Orlando, Florida, in December 2019 by Dr. Garcia-Manero.6

Astex’s parent company, Otsuka Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd. previously announced that, subject to regulatory approvals, commercialization of oral INQOVI in the U.S. and Canada will be conducted by Taiho Oncology, Inc. and Taiho Pharma Canada, Inc. respectively.

“Our partnership with Astex is a demonstration of the commitment that Taiho Oncology has to bringing new therapeutic options to patients with cancer,” said Tim Whitten, president and chief executive officer of Taiho Oncology, Inc. “The approval of INQOVI makes the possibility of at-home hypomethylating agent treatment of intermediate and high-risk MDS and CMML a reality, enabling patients to take their medication from the convenience and comfort of their home. This is especially significant during the COVID-19 pandemic, allowing patients to potentially reduce the number of office visits needed for current IV treatment administration. We look forward to working with all healthcare professionals to help deliver the first new oral HMA treatment alternative for patients with intermediate and high-risk MDS and CMML in nearly fifteen years.”

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