FDA Expands Approval of Servier’s Therapy for Rare Form of Blood Cancers

Rare Daily Staff

The U.S. Food and Drug Administration approved Servier Pharmaceuticals’ Tibsovo for the treatment of adult patients with relapsed or refractory (R/R) myelodysplastic syndromes.

The approval is for patients with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. It is the first targeted therapy approved for this indication. The agency also approved the Abbott RealTime IDH1 Assay as a companion diagnostic for the selection of R/R MDS patients with an IDH1 mutation.

Myelodysplastic syndromes (MDS) are a rare form of blood cancers that can occur when the mutations in the bone marrow progenitor cells lead to insufficient numbers of healthy blood cells. Approximately 60,000 to 170,000 people live with MDS in the United States, with an estimated 87,000 new cases each year worldwide. About 3.6 percent of patients with MDS have an IDH1 mutation.

“Today’s approval represents an important treatment advancement for rare blood cancers, and more specifically, patients with relapsed or refractory MDS who have an IDH1 mutation,” said Richard Pazdur, director of the 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.

Tibsovo was previously approved for certain adults with newly-diagnosed acute myeloid leukemia (AML), relapsed or refractory AML, and locally advanced or metastatic cholangiocarcinoma. The Abbott RealTime IDH1 Assay was also previously approved as a companion diagnostic to identify AML patients with an IDH1 mutation for treatment with Tibsovo or Rezlidhia.

The effectiveness of Tibsovo for this new indication was evaluated in an open-label, single-arm, multicenter study of 18 adult patients with relapsed or refractory MDS with an IDH1 mutation. IDH1 mutations were detected in peripheral blood or bone marrow by a local or central diagnostic test and confirmed retrospectively using the Abbott RealTime IDH1 Assay.

The main efficacy outcome measures were the rate of complete remission or partial remission, the duration of complete remission or partial remission and the rate of conversion from transfusion dependence to transfusion independence. The complete remission or partial remission rate was 39 percent. All observed responses were complete remissions and the median duration of complete remission ranged from 1.9 to 80.8 months. For patients who achieved a complete remission, the median time to complete remission was 1.9 months. Among the nine patients who required transfusions of blood or platelets due to MDS at the start of the study, 67 percent no longer required transfusions after treatment with Tibsovo.

The most common side effects were similar to common side effects seen with Tibsovo monotherapy for patients with AML. This includes diarrhea, constipation, nausea, joint pain, fatigue, cough, muscle aches and rash. Tibsovo may also cause a condition which can lead to abnormal heart rhythms.

The prescribing information for Tibsovo includes a boxed warning that an adverse reaction known as differentiation syndrome can occur and can be fatal if not treated. Signs and symptoms of differentiation syndrome may include fever, difficulty breathing, low oxygen levels, inflammation in the lungs, fluid around the lungs or heart, rapid weight gain, swelling, or multi-organ dysfunction. At first suspicion of symptoms, health care providers should treat patients with corticosteroids and monitor patients closely until symptoms go away.

Tibsovo was granted Priority Review designation, Breakthrough Therapy designation, and Orphan Drug designation.