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.
Approximately 60,000 to 170,000 people in the United States live with MDS, with an estimated 87,000 new cases reported worldwide each year. Among MDS patients, about 3.6 percent have an IDH1 mutation. The FDA’s approval of Tibsovo marks a significant advancement in the treatment of rare blood cancers, particularly for patients with R/R MDS who possess the IDH1 mutation.
According to 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, “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.” This approval demonstrates the FDA’s commitment to promoting scientific innovation and developing safe and effective therapies for patients with rare cancers through its Oncology Center of Excellence Rare Cancers Program.
The Efficacy of Tibsovo
Tibsovo’s effectiveness for this new indication was evaluated in an open-label, single-arm, multicenter study involving 18 adult patients with relapsed or refractory MDS who possessed the IDH1 mutation. The IDH1 mutations were identified in peripheral blood or bone marrow through local or central diagnostic tests and later confirmed retrospectively using the Abbott RealTime IDH1 Assay, which was also approved as a companion diagnostic for the selection of R/R MDS patients with an IDH1 mutation.
In the study, Tibsovo was administered orally at a starting dose of 500 milligrams daily for 28-day cycles until disease progression, the development of unacceptable toxicity, or the patient underwent a bone marrow transplant. 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 study results showed that the rate of complete remission or partial remission was 39% (7/18). All observed responses were complete remissions, with the median duration of complete remission ranging from 1.9 to 80.8 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 needed transfusions after receiving treatment with Tibsovo.
Safety Profile and Side Effects
Like any medication, Tibsovo comes with its own set of potential side effects. The most common side effects observed were similar to those seen with ivosidenib monotherapy for patients with acute myeloid leukemia (AML). These side effects include diarrhea, constipation, nausea, joint pain, fatigue, cough, muscle aches, and rash. It’s important to note that Tibsovo may also lead to a condition called QTc prolongation, which can cause abnormal heart rhythms.
To ensure the safe usage of Tibsovo, the prescribing information includes a boxed warning regarding the potential occurrence of a severe adverse reaction known as differentiation syndrome. If left untreated, differentiation syndrome can be fatal. 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 dysfunction in the liver, kidney, or other organs. Healthcare providers should promptly treat patients suspected of experiencing differentiation syndrome with corticosteroids and closely monitor them until symptoms subside.
Previous Approvals and Designations
Prior to its approval for the treatment of R/R MDS, Tibsovo had already received FDA approval for certain adults with newly-diagnosed AML, relapsed or refractory AML, and locally advanced or metastatic cholangiocarcinoma. The Abbott RealTime IDH1 Assay, approved as a companion diagnostic for identifying AML patients with an IDH1 mutation, was also previously approved for use in conjunction with Tibsovo or Rezlidhia (olutasidenib), another therapy for AML.
The FDA’s approval of Tibsovo for the treatment of relapsed or refractory MDS with an IDH1 mutation represents a significant milestone in the battle against rare blood cancers. With limited treatment options available, this targeted therapy offers hope to patients who have exhausted other alternatives. The efficacy demonstrated in clinical trials, along with the safety measures and precautions outlined by the FDA, make Tibsovo a promising addition to the arsenal of treatments for MDS. As we continue to advance scientific innovation and prioritize the development of therapies for rare cancers, Tibsovo’s approval is a testament to the dedication and commitment of healthcare professionals and researchers in the fight against these devastating diseases.
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 Therapydesignation and Orphan Drug designation for the indication noted above. Orphan drug designation provides incentives to assist and encourage drug development for rare diseases.
To learn more about yyelodysplastic syndromes and other rare cancers, visit https://checkrare.com/diseases/cancers
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