FDA Approval: Enasidenib (Idhifa) for Leukemia

A mutation that stops blood cells growing up

Acute myeloid leukemia, or AML, is a cancer of the blood and bone marrow. NCI describes it as a disease in which the marrow makes a large number of abnormal blood cells, and notes that it usually gets worse quickly if untreated.

The underlying failure is one of maturation. Healthy marrow turns stem cells into finished red cells, white cells and platelets. In AML the process stalls partway. Immature cells, called blasts, pile up and crowd out everything the body actually needs.

Some AML carries a mutation in a gene called IDH2, short for isocitrate dehydrogenase 2. The normal enzyme does ordinary metabolic work. The mutant version makes a molecule called 2-hydroxyglutarate, or 2-HG, and 2-HG is what keeps the cells stuck as blasts.

Blocking the enzyme rather than killing the cell

Enasidenib, sold as Idhifa, is a small molecule that inhibits the IDH2 enzyme.

Its label describes the selectivity precisely. It targets the mutant IDH2 variants R140Q, R172S and R172K at roughly 40-fold lower concentrations than the normal enzyme. Blocking the mutant enzyme lowered 2-HG and induced myeloid differentiation in laboratory and animal models.

In blood samples from patients with IDH2-mutated AML, the label reports, enasidenib lowered 2-HG, reduced blast counts and raised the share of mature myeloid cells.

That is a different mechanism from chemotherapy. The drug is not primarily poisoning dividing cells. It is releasing a block, so the leukemia cells finish growing up and behave more like normal blood cells.

What the FDA approved, and on what evidence

On August 1, 2017 the FDA approved Idhifa for adults with relapsed or refractory AML carrying an IDH2 mutation. Relapsed means the leukemia came back. Refractory means it never went away.

The approval came with a companion diagnostic, the RealTime IDH2 Assay, which detects IDH2 mutations in blood or bone marrow. No mutation, no treatment.

Efficacy rested on a single-arm trial of 199 patients. Single-arm means there was no comparison group; everyone received the drug.

With at least six months of treatment, 19 percent of patients reached complete remission, lasting a median of 8.2 months. Complete remission means no evidence of disease and full recovery of blood counts. Another 4 percent reached complete remission with partial hematologic recovery, lasting a median of 9.6 months.

There was a fourth number. Of the 157 patients who needed blood or platelet transfusions when they started, 34 percent no longer needed them afterward. Coming off transfusions is a change a person feels week to week.

The warning that sits on the front of the label

Idhifa carries a boxed warning, the FDA's most serious, for differentiation syndrome. It can be fatal if untreated.

Differentiation syndrome happens because the drug works. As blocked cells suddenly mature all at once, they release inflammatory signals into the body.

The label lists the symptoms: fever, shortness of breath, acute respiratory distress, infiltrates in the lungs, fluid around the lungs or heart, rapid weight gain, swelling, swollen lymph nodes, bone pain, and liver, kidney or multi-organ trouble.

The instruction is to act on suspicion, not on proof. At the first sign, teams start corticosteroids and monitor circulation until the symptoms resolve.

Common side effects reported at approval were nausea, vomiting, diarrhea, raised bilirubin and reduced appetite. Idhifa can harm a developing fetus or a newborn.

When to get checked

AML moves fast. NCI notes that symptoms often develop between four and six weeks before diagnosis, and that early signs can look like flu.

NCI says to check with a doctor for:

• Weakness or feeling tired.
• Fever.
• Infection.
• Paleness or loss of normal skin color.
• Bleeding.

The pattern that should not wait is a combination. Fever plus unexplained bruising, or bleeding gums plus deep exhaustion over a few weeks, is a same-week appointment and a full blood count. Our page on acute myeloid leukemia symptoms goes through each one.

Diagnosis starts with a complete blood count, then a bone marrow sample. Genetic testing of that sample is what finds IDH2 and other mutations. Our page on biomarker testing covers what those tests decide.

The numbers around this disease

For 2026 the American Cancer Society projects 22,720 new US cases of acute myeloid leukemia and 11,500 deaths; SEER carries the same figures. NCI's own SEER data put the median age at diagnosis at 70. Five-year relative survival for cases from 2016 to 2022 is 33.4 percent.

That last figure has moved a long way. In the mid-1970s SEER recorded five-year relative survival in the single digits for AML.

The figures are averages across everyone in the registry: all ages, all subtypes, all treatments. AML behaves very differently depending on which mutations a person's leukemia carries, so a single average tells no individual anything about their own case. Our page on acute myeloid leukemia sets out how those subtypes differ.

What this approval cannot tell you

The trial had no control group. Without one, there is no way to say how these patients would have fared on something else, and no survival comparison exists.

Nineteen percent is the complete remission rate. Most people in the trial did not reach one.

Median response duration of 8.2 months is a middle value, not a length anyone is promised. Half of responders had shorter responses.

The drug only applies to AML with an IDH2 mutation, confirmed by an approved test. That is a minority of AML.

And this was a 2017 approval in a field that moves quickly. Where enasidenib now sits among AML options, and whether it fits any particular person, is a current clinical question rather than something a 2017 press release settles.

Sources

• FDA, FDA approves new targeted treatment for relapsed or refractory acute myeloid leukemia, 1 August 2017 — https://www.fda.gov/news-events/press-announcements/fda-approves-new-targeted-treatment-relapsed-or-refractory-acute-myeloid-leukemia
• FDA prescribing information for IDHIFA, via the openFDA drug label API — https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22IDHIFA%22&limit=1
• NCI PDQ, Acute Myeloid Leukemia Treatment (Patient Version) — https://www.cancer.gov/types/leukemia/patient/adult-aml-treatment-pdq
• SEER Cancer Stat Facts, Acute Myeloid Leukemia — https://seer.cancer.gov/statfacts/html/amyl.html

How this article was prepared

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

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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