FDA Approval: Ivosidenib (Tibsovo) for Leukemia

The approval in plain terms

On July 20, 2018, the Food and Drug Administration approved Tibsovo, the brand name for ivosidenib, under New Drug Application 211192. The review was a priority review, and the drug carried orphan status, a designation for treatments of rare diseases.

The indication was tightly drawn. Tibsovo was approved for adults with relapsed or refractory acute myeloid leukemia, or AML, that carries a susceptible IDH1 mutation as detected by an FDA-approved test.

Every clause in that sentence does work. Relapsed means the leukemia came back. Refractory means it never responded. And the IDH1 mutation is not optional: without it, this drug has no reason to be there.

What IDH1 does when it goes wrong

IDH1 stands for isocitrate dehydrogenase 1. Normally it is an ordinary metabolic enzyme, part of how cells process energy.

When the gene is mutated, the enzyme starts making a different molecule instead. That molecule builds up and interferes with the chemical tags that tell a cell when to stop dividing and start maturing into a working blood cell. The leukemia cells get stuck in an immature state and keep multiplying.

Ivosidenib blocks the mutated enzyme. The cells are then able to finish maturing. That is a genuinely different idea from chemotherapy, which kills dividing cells. It also explains the drug's most dangerous side effect.

Which mutation a person has is found by testing, not guessed. FDA approved a companion diagnostic alongside the drug, the Abbott RealTime IDH1 assay. NCI reports that roughly 6 to 10 percent of people with AML carry the relevant IDH1 mutation. Our page on biomarker testing explains what those tests look for.

The trial behind it

The evidence came from Study AG120-C-001, registered as NCT02074839. It was open-label and single-arm. Everyone knew what they were getting, and there was no comparison group. It enrolled 174 adults with relapsed or refractory AML and an IDH1 mutation, all taking 500 mg daily. The trial was funded by Agios Pharmaceuticals, which made the drug. That was the amount everyone in the study took, not a guide to what you should take.

That was the study amount. Your own haematology team sets your dose, and they hold or reduce it when problems such as differentiation syndrome appear.

The people in it were not newly diagnosed. Median age was 67. The median number of previous treatments was two. Sixty-three percent depended on blood transfusions at the start. Thirty-seven percent had leukemia that had never responded to first treatment. Twenty-three percent had already had a stem cell transplant.

What the results were

The efficacy measures were remission rates, how long remissions lasted, and whether people stopped needing transfusions.

Complete remission, defined as under 5 percent immature cells in the bone marrow, no evidence of disease and full recovery of blood counts, occurred in 43 people, or 24.7 percent, with a 95 percent confidence interval of 18.5 to 31.8. The median duration was 10.1 months.

Adding complete remission with partial recovery of blood counts brought the combined rate to 57 people, or 32.8 percent, with a confidence interval of 25.8 to 40.3. The median duration of that combined response was 8.2 months. Median time to first response was 2 months, and everyone who responded did so within 6 months.

Among the 110 people dependent on red cell or platelet transfusions at the start, 41, or 37.3 percent, became free of both during a 56-day window. Twenty-one people, 12 percent, went on to a stem cell transplant.

The boxed warning

Ivosidenib carries a boxed warning for differentiation syndrome, and it appeared in 19 percent of the 179 people in the safety population.

The mechanism is the drug working. As leukemia cells rapidly mature and multiply, they can flood the body with inflammatory signals. Label-listed symptoms include a rising white cell count without infection, swelling, fever, breathlessness, fluid around the lungs or heart, low blood pressure, low oxygen, fluid in the lungs, rash and rising creatinine.

Timing matters: it occurred as early as one day and as late as three months after starting. Treatment is corticosteroids and monitoring, and of the 34 people who developed it, 27, or 79 percent, recovered after treatment or after pausing the drug.

Other serious reactions reported in at least 5 percent were leukocytosis, a high white cell count, at 10 percent, and QT prolongation on the electrocardiogram at 7 percent. QT prolongation is a change in the heart's electrical recovery that can lead to dangerous rhythms, which is why heart tracings are monitored.

The wider picture for AML

The American Cancer Society projects 22,720 new cases of acute myeloid leukemia in the United States in 2026 and 11,500 deaths; SEER, the federal cancer statistics program, publishes that projection. SEER's own measurements put five-year relative survival at 33.4 percent for people diagnosed from 2016 through 2022. About 0.5 percent of people are diagnosed at some point in life, and roughly 83,000 Americans were living with AML in 2023.

Those numbers cover all AML, at all ages and all genetic subtypes. They are group statistics about people diagnosed years ago and describe no individual.

What to keep in perspective

• The trial had no comparison group. A single-arm study can measure how many people responded. It cannot show how they would have fared on something else. NCI quoted an AML specialist, Dr. Roland Walter of Fred Hutchinson Cancer Research Center, making exactly that point: there were no comparative data against standard salvage therapy.
• Remission rates are not survival. This approval rested on remission and transfusion independence, not on evidence that people lived longer than they otherwise would have.
• The mutation is the gate. Without an IDH1 mutation found on an approved test, this indication does not apply.
• Responses were measured in months, in a group that had already exhausted other options.
• Labels move. This describes the July 2018 approval, and ivosidenib's label has been revised since.

Our guides to clinical trial phases and leukemia fill in the background, and our targeted therapy page turns this into things worth raising with a care team.

Sources

• https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=211192
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211192s000lbl.pdf
• https://www.cancer.gov/news-events/cancer-currents-blog/2018/ivosidenib-aml-fda-approval
• https://www.cancer.gov/about-cancer/treatment/drugs/ivosidenib
• https://seer.cancer.gov/statfacts/html/amyl.html

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

See an error, old source, or unclear wording? Tell us.