FDA Approves Oral Combination of Dacogen and Cedazuridine for Patients with Myelodysplastic Syndromes

The Food and Drug Administration approved the oral combination of Inquovi (Dacogen [decitabine] and cedazuridine) for adult patients with myelodysplastic syndromes (MDS) in the following subtypes:

• previously treated and untreated, de novo and secondary MDS with the following French, American and British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML])
• intermediate-1, intermediate-2 and high-risk International Prognostic Scoring System groups.

This approval is the result of two open-label, randomized, crossover trials investigating the Inqovi combination. The first trial, ASTX727-01-B, involved 80 adult patients with CMML or MDS with an International Prognostic Scoring System [IPSS] score of Intermediate-1, Intermediate-2, or high-risk. The second trial, ASTX727-02, 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.

In both trials, patients were split into two groups: one group received Inqovi (35 mg of Dacogen and 100 mg cof edazuridine) orally in cycle 1 and decitabine 20 mg/m2 intravenously in cycle 2, while the second group received the reverse sequence.

Both Inqovi and intravenous Dacogen were administered once daily on days one through five of a 28-day cycle. Starting with cycle 3, all patients received Inqovi orally once daily on days one through five of each 28-day cycle until disease progression or unacceptable toxicity.

In the first trial, investigators found a complete response (CR) rate of 18% and median duration of CR of 8.7 months. The second trial demonstrated that 21% of patients achieved CR. The median duration of CR was 7.5 months.

The most common side effects 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 increased transaminase.

The most common grade 3 or 4 laboratory abnormalities, which occurred in 50% or more of patients, were leukocytes decreased, platelet count decreased, neutrophil count decreased and hemoglobin decreased. The overall safety profile of oral Inqovi was similar to IV decitabine.

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

The recommended Inqovi dose is one tablet (35 mg Dacogen and 100 mg cedazuridine) orally on an empty stomach once daily on days one through five of each 28‑day cycle.

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