The U.S. Food and Drug Administration ( FDA ) has approved Tibsovo ( Ivosidenib ) in combination with Azacitidine for the treatment of patients with newly diagnosed IDH1-mutated acute myeloid leukemia ( AML ) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.
Tibsovo is the first therapy targeting cancer metabolism approved in combination with Azacitidine for patients with newly diagnosed IDH1-mutated acute myeloid leukemia.
The AGILE trial was the only phase 3 trial designed specifically for newly diagnosed patients with IDH1-mutated acute myeloid leukemia who are ineligible for intensive chemotherapy.
The supplemental New Drug Application ( sNDA ) for Tibsovo has received Priority Review and was reviewed by the FDA under its Real-Time Oncology Review ( RTOR ) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.
The expanded approval of Tibsovo is supported by data from the AGILE study, a global, phase 3 trial in patients with previously untreated IDH1-mutated acute myeloid leukemia.
Results from the AGILE trial have demonstrated a statistically significant improvement in event-free survival ( EFS ) ( hazard ratio [ HR ] = 0.35 [ 95% CI 0.17, 0.72 ], 2-sided p-value = 0.0038 ) and overall survival ( OS ) ( HR = 0.44 [ 95% CI 0.27, 0.73 ]; 2-sided p = 0.0010 ).
Tibsovo plus Azacitidine treatment resulted in a threefold improvement in median overall survival ( 24 months ) compared to placebo plus Azacitidine ( 7.9 months ) as a first-line treatment for IDH1-mutated acute myeloid leukemia.
The combination of Tibsovo plus Azacitidine has demonstrated a safety profile consistent with previously published data.
The most common adverse reactions ( 10% or more ) in newly diagnosed patients with acute myeloid leukemia receiving Tibsovo in combination with Azacitidine were nausea, vomiting, electrocardiogram QT prolonged, insomnia, differentiation syndrome, leukocytosis, hematoma, hypertension, arthralgia, dyspnea, and headache.
The select laboratory abnormalities ( 10% or more ) were leukocytes decreased, platelets decreased, hemoglobin decreased, neutrophils decreased, lymphocytes increased, glucose increased, phosphate decreased, aspartate aminotransferase increased, magnesium decreased, alkaline phosphatase increased, and potassium increased.
The recommended dosage of Tibsovo for newly diagnosed IDH1-mutated acute myeloid leukemia is 500mg once daily via oral administration.
Tibsovo is also approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory acute myeloid leukemia, and for adults with newly diagnosed IDH1-mutated AML who are greater than or equal to 75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy.
In 2021, Tibsovo has garnered its first approval by FDA in a non-hematologic malignancy for patients with previously treated IDH1-mutated cholangiocarcinoma.
Acute myeloid leukemia is a difficult-to-treat cancer of the blood and bone marrow and is one of the most common types of leukemia in adults with approximately 20,000 new cases estimated in the U.S. and 43,000 cases in Europe each year.
IDH1 mutations are present in about 6 to 10% of acute myeloid leukemia cases.
AML incidence significantly increases with age, and the median age of diagnosis is 68.2
The five-year survival rate is approximately 29.5%. ( Xagena )
Source: Servier, 2022