FDA approves Inqovi as at-home treatment for myelodysplastic syndrome
The FDA approved the oral combination of decitabine and cedazuridine for treatment of adults with myelodysplastic syndrome.
The approval of decitabine and cedazuridine (Inqovi, Astex Pharmaceuticals) applies to patients with previously treated or untreated, de novo and secondary myelodysplastic syndrome with the following French-American-British subtypes: refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, or chronic myelomonocytic leukemia (CMML). It also applies to intermediate-1, intermediate-2 and high-risk International Prognostic Scoring System (IPSS) groups.
“The FDA remains committed to providing additional treatments to patients during the coronavirus pandemic. In this case, the FDA is making available an oral outpatient treatment option that can reduce the need for frequent visits to health care facilities,” Richard Pazdur, MD, director of FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press release.
The FDA based the approval 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.
Researchers in both trials randomly assigned half of patients to 35 mg decitabine and 100 mg cedazuridine orally, then decitabine dosed at 20 mg/m2 IV in the second cycle. Both 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.
The oral combination of decitabine and cedazuridine exhibited a safety profile similar to that of IV decitabine.
The most common adverse events reported with the oral combination 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 increase.
The most common grade 3 or grade 4 laboratory abnormalities included decreased leukocytes, platelet counts, neutrophil counts or hemoglobin.
The FDA had granted priority review to this application.