Pharma Focus Europe

The FDA Grants Approval for a Novel Therapy Targeting Rare Blood Cancers Known as Myelodysplastic Syndromes

Wednesday, October 25, 2023

Today, the U.S. Food and Drug Administration (FDA) has granted its approval to Tibsovo (ivosidenib) for the treatment of adult patients with relapsed or refractory (R/R) myelodysplastic syndromes (MDS) who carry an isocitrate dehydrogenase-1 (IDH1) mutation as confirmed by an FDA-sanctioned test. This is a noteworthy development as it marks the first targeted therapy approved for this specific condition. Alongside Tibsovo, the Abbott RealTime IDH1 Assay has also received approval as a companion diagnostic tool for identifying R/R MDS patients with an IDH1 mutation.

MDS is a rare subgroup of blood cancers that arise when mutations in bone marrow progenitor cells, responsible for blood cell formation, lead to an insufficient number of healthy blood cells. In the United States, an estimated 60,000 to 170,000 individuals live with MDS, with approximately 87,000 new cases occurring globally each year. It's worth noting that around 3.6 percent of MDS patients carry an IDH1 mutation.

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, expressed the significance of this approval, stating, "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. 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 had previously gained approval for specific adult patients with newly-diagnosed Acute Myeloid Leukemia (AML), as well as for those with relapsed or refractory AML and locally advanced or metastatic cholangiocarcinoma. Furthermore, the Abbott RealTime IDH1 Assay had previously been approved as a companion diagnostic tool for identifying AML patients with an IDH1 mutation who could benefit from Tibsovo or Rezlidhia (olutasidenib) treatment.

The effectiveness of Tibsovo for this new indication was assessed in an open-label, single-arm, multicenter study involving 18 adult patients with relapsed or refractory MDS who had an IDH1 mutation. IDH1 mutations were identified in peripheral blood or bone marrow through local or central diagnostic tests and were later confirmed using the Abbott RealTime IDH1 Assay. Tibsovo was administered orally at a starting dose of 500 milligrams daily, continuously for 28-day cycles, until disease progression, unacceptable toxicity, or bone marrow transplantation.

The primary outcome measures for efficacy included the rates of complete remission, partial remission, the duration of complete remission or partial remission, and the rate of transitioning from transfusion dependence to transfusion independence. Notably, the complete remission or partial remission rate was 39% (7 out of 18 patients). All observed responses were complete remissions, with the duration of complete remission ranging from 1.9 to 80.8 months. Among the nine patients who required blood or platelet transfusions due to MDS at the study's onset, six (67%) no longer required transfusions after Tibsovo treatment.

The most common side effects were in line with those seen with ivosidenib monotherapy for AML patients, which included diarrhea, constipation, nausea, joint pain, fatigue, cough, muscle aches, and rash. It's important to note that Tibsovo may also lead to a condition that can cause abnormal heart rhythms called QTc prolongation.

The prescribing information for Tibsovo includes a boxed warning about the potential occurrence of a severe reaction known as differentiation syndrome, which can be fatal if left untreated. Signs and symptoms of differentiation syndrome may encompass fever, difficulty breathing (dyspnea), low oxygen levels, lung inflammation (radiographic pulmonary infiltrates), fluid around the lungs or heart (pleural or pericardial effusions), rapid weight gain, swelling (peripheral edema), or dysfunction of the liver (hepatic), kidneys (renal), or multiple organs. Healthcare providers should initiate treatment with corticosteroids and closely monitor patients upon suspicion of such symptoms until they resolve.

Tibsovo received Priority Review designation, which implies that the FDA aims to take action on an application within six months if the drug, when approved, significantly enhances the safety or efficacy of treating, diagnosing, or preventing a serious condition. Additionally, Tibsovo was granted FDA Breakthrough Therapy designation and Orphan Drug designation for the specified indication, which provides incentives to support and stimulate drug development for rare diseases.

The FDA has granted approval for Tibsovo to Servier Pharmaceuticals LLC, and the RealTime IDH1 Assay to Abbott Laboratories.



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