FDA Approves Oral Decitabine and Cedazuridine for MDS

The FDA approved an oral combination of decitabine and cedazuridine (Inqovi) for adults with myelodysplastic syndromes (MDS). The combination can be taken at home.

The combination was approved for the following subtypes: previously treated or untreated, de novo and secondary MDS with French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML); as well as intermediade-1, intermediate-2, and high-risk International Prognostic Scoring System groups.

The approval is based on 2 open-label, randomized, crossover trials that compared exposure and safety in the first 2 cycles between the oral Inqovi and intravenous (IV) decitabine, as well as description of disease response with Inqovi.

• Trial ASTX727-01-B (NCT02103478) included 80 adult patients with MDS (International Prognostic Scoring System [IPSS] Intermediate-1, Intermediate-2, or high-risk) or CMML
• ASTX727-02 (NCT03306264) included 133 adult patients with MDS or CMML, including all French, American, and British classification criteria and IPSS Intermediate-1, Intermediate-2, or high-risk prognostic scores

Patients on both trials were randomized 1:1 to receive the investigative drug combination (35 mg decitabine and 100 mg cedazuridine) in cycle 1 and 20mg/m² of decitabine intravenously in cycle 2, or the reverse sequence. The oral combination and IV decitabine were administered once a day on days 1 through 5 of a 28-day cycle. At cycle 3, all patients received the combination orally once daily on days 1-28 of the 28-day cycle until progression or unacceptable toxicity.

In the first trial, Inqovi had a complete response (CR) rate of 18% and a median duration of response of 8.7 months (range, 1.1-18.2). Forty-nine percent of patients (n=20) of patients who were dependent on red blood cell and/or platelet transfusions at baseline became independent of RBC and platelet transfusions during any consecutive 56-day post-baseline period. Twenty-five patients remained transfusion-independent during any consecutive 56-day baseline period.

Common adverse events that occurred in 20% or more of patients included fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and transaminase increased.

Common grade 3 or 4 laboratory abnormalities (occurring in 50% or more of patients) were eukocytes decreased, platelet count decreased, neutrophil count decreased, and hemoglobin decreased.

The overall safety profile of oral Inqovi was similar to IV decitabine.