General Information

Inqovi is a combination of decitabine, a nucleoside metabolic inhibitor, and cedazuridine, a cytidine deaminase inhibitor.

Inqovi is specifically indicated for the treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-AmericanBritish subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.

Inqovi is supplied as a tablet for oral administration. The recommended dosage of Inqovi is 1 tablet (35 mg decitabine and 100 mg cedazuridine) taken orally once daily on Days 1 through 5 of each 28-day cycle. Take Inqovi on an empty stomach. Take Inqovi at the same time each day. Swallow tablets whole. Do not cut, crush, or chew tablets.

Mechanism of Action

Inqovi is a combination of decitabine and cedazuridine. 

Decitabine is a nucleoside metabolic inhibitor that is believed to exert its effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation and/or apoptosis. Decitabine inhibits DNA methylation in vitro, which is achieved at concentrations that do not cause major suppression of DNA synthesis. Decitabine-induced hypomethylation in cancer cells may restore normal function to genes that are critical for the control of cellular differentiation and proliferation. In rapidly dividing cells, the cytotoxicity of decitabine may also be attributed to the formation of covalent adducts between DNA methyltransferase and decitabine incorporated into DNA. Non-proliferating cells are relatively insensitive to decitabine.

Cytidine deaminase (CDA) is an enzyme that catalyzes the degradation of cytidine, including the cytidine analog decitabine. High levels of CDA in the gastrointestinal tract and liver degrade decitabine and limit its oral bioavailability. Cedazuridine is a CDA inhibitor. Administration of cedazuridine with decitabine increases systemic exposure of decitabine.

Side Effects

Adverse effects associated with the use of Inqovi may include, but are not limited to, the following:

• fatigue
• constipation
• hemorrhage
• myalgia
• mucositis
• arthralgia
• nausea
• dyspnea
• diarrhea
• rash
• dizziness
• febrile neutropenia
• edema
• headache
• cough
• decreased appetite
• upper respiratory tract infection
• pneumonia
• transaminase increased
• Grade 3 or 4 laboratory abnormalities (≥ 50%): leukocytes decreased, platelet count decreased, neutrophil count decreased, and hemoglobin decreased

Clinical Trial Results

The FDA approval of Inqovi was based on results of two randomized, open-label crossover trials. The ASTX727-01-B trial included 80 adults with myelodysplastic syndrome (IPPS intermediate-1, intermediate-2 or high risk) or CMML. The ASTX727-02 trial included 133 adults with myelodysplastic syndrome or CMML, including those with all French-American-British classification criteria and IPSS prognostic scores. Patients in both trials were randomly assigned to 35 mg decitabine and 100 mg cedazuridine orally, then decitabine dosed at 20 mg/m2 IV in the second cycle. Both treatments were administered once daily on days 1 through 5 of 28-day cycles. The other half of patients received the reverse sequence. Starting with the third cycle, all patients received decitabine and cedazuridine orally once daily on days 1 through 5 of each 28-day cycle. Treatment continued until unacceptable toxicity or disease progression. Results of both trials showed similar drug concentrations between the oral combination of decitabine and cedazuridine and IV decitabine. Approximately half of the patients who had been dependent on transfusions no longer required red blood cell or platelet transfusions during any consecutive 8-week post-baseline period.