Silver Spring, MD / October 24, 2023 / Today, the U.S. Food and Drug Administration approved Tibsovo (ivosidenib) for the treatment of adult patients with relapsed or refractory (R/R) myelodysplastic syndromes (MDS) with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. This 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. 

MDS are a rare form of blood cancers that can occur when the mutations in the bone marrow progenitor cells (cells that form blood) lead to insufficient numbers of healthy blood cells. Approximately 60,000 to 170,000 people live with MDS in the U.S., 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, M.D., 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. “Through the FDA’s Oncology Center of Excellence Rare Cancers Program, we remain committed to promoting scientific innovation and advancing the development of safe and effective novel therapies to treat patients with rare cancers.”

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 (olutasidenib).

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. Tibsovo was given orally at a starting dose of 500 milligram daily continuous for 28-day cycles until disease progression, development of unacceptable toxicity or undergoing bone marrow transplantation. 

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% (7/18). 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, six (67%) no longer required transfusions after treatment with Tibsovo. 

The most common side effects were similar to common side effects seen with ivosidenib 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 called QTc prolongation. 

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 (dyspnea), low oxygen levels, inflammation in the lungs (radiographic pulmonary infiltrates), fluid around the lungs or heart (pleural or pericardial effusions), rapid weight gain, swelling (peripheral edema) or liver (hepatic), kidney (renal) 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, under which the FDA’s goal is to take action on an application within six months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition. Tibsovo also received FDA Breakthrough Therapy designation and Orphan Drug designation for the indication noted above. Orphan drug designation provides incentives to assist and encourage drug development for rare diseases.

The FDA granted the approval of Tibsovo to Servier Pharmaceuticals LLC. The FDA granted the approval of the RealTime IDH1 Assay to Abbott Laboratories.

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The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, radiation-emitting electronic products, and for regulating tobacco products.