Ruxolitinib (Jakafi) FDA Approval History: Every Indication and Date

In brief

Ruxolitinib is sold as Jakafi. The FDA approved it on November 16, 2011, for intermediate- or high-risk myelofibrosis. Three more uses followed. Polycythemia vera came on December 4, 2014. Steroid-refractory acute graft-versus-host disease came on May 24, 2019. Chronic graft-versus-host disease came on September 22, 2021. Those four are the whole FDA approval history under NDA 202192.

The approval history

Date	Indication	Evidence
November 16, 2011	Intermediate or high-risk myelofibrosis in adults	Two randomized phase 3 trials (spleen volume)
December 4, 2014	Polycythemia vera in adults after inadequate response to or intolerance of hydroxyurea	RESPONSE, randomized, 222 patients
May 24, 2019	Steroid-refractory acute GVHD, adults and children 12 and older	Study INCB 18424-271, single-arm, 49 patients
September 22, 2021	Chronic GVHD after failure of one or two lines of systemic therapy, adults and children 12 and older	REACH-3, randomized, 329 patients

Drugs@FDA records the 2011 decision as a full approval, not an accelerated one. It carried priority review and orphan drug status. The approval letter names the covered conditions: primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Each later use was added as a supplement to the same application.

What the drug does

Cells in the bone marrow take growth instructions through a relay called the JAK-STAT pathway. Janus kinases sit just inside the cell wall. They catch the signal from outside and pass it in to the nucleus, where the genes for making blood cells switch on.

In myelofibrosis and polycythemia vera that relay is stuck partly open. The usual cause is a gene change called JAK2 V617F. So the marrow keeps making cells nobody asked for. Scar tissue slowly crowds out the space where normal blood cells form.

Ruxolitinib blocks JAK1 and JAK2 and quiets the relay. It does that whether or not JAK2 is mutated. That is why the label does not require a gene test first, which is unusual for a targeted drug.

One note on names. Myelofibrosis and polycythemia vera are myeloproliferative neoplasms, blood cancers of the bone marrow. They are close relatives of leukemia and are treated by the same specialists. But they are not leukemia, and this drug is not approved to treat leukemia.

What the trials measured

The myelofibrosis approval rested on two randomized phase 3 trials. Both used spleen size as the main endpoint.

In the placebo-controlled trial, 65 of 155 people on ruxolitinib, or 42%, had their spleen volume shrink by at least 35% at week 24. On placebo, 1 of 154 did. In the trial against best available therapy, 41 of 146, or 29%, reached that mark at week 48. None of the 73 in the comparison group did.

Spleen size matters here in a way it does not in most cancers. When scarring pushes blood production into the spleen, the organ can swell until it presses on the stomach. That causes pain, early fullness, and weight loss. Shrinking it is a benefit you can feel.

The RESPONSE trial covered polycythemia vera. It enrolled 222 people whose disease was not controlled by hydroxyurea. The main endpoint joined two things: keeping the hematocrit down without needing blood removed between weeks 8 and 32, and shrinking the spleen by 35% or more at week 32. Twenty-five people on ruxolitinib, or 23%, managed both. One person on best available therapy did.

For steroid-refractory acute GVHD, a single-arm study of 49 patients reported a day-28 response rate of 57.1%. For chronic GVHD, REACH-3 randomized 329 people. The response rate was 70% with ruxolitinib and 57% with best available therapy. Responses lasted a median of 4.2 months against 2.1 months.

Read those endpoints carefully. None of the four approvals rested on people living longer. They rested on spleen size, blood counts, and response rates. Those are real benefits, but they are different ones.

How it is taken and what it does to you

Ruxolitinib is a tablet taken twice a day. For myelofibrosis the starting amount depends on the platelet count, with lower platelets meaning a lower starting dose. Polycythemia vera has its own, separate starting amount. An extended-release form, Jakafi XR, is now on the label too.

The dose is tied to platelets because the drug's main effect is also its main problem. Blocking JAK signals slows blood cell production across the board. So low platelets and anemia are the most common adverse reactions, each in more than 20% of patients. Bruising, dizziness, headache, and diarrhea occur in at least 15%. The label's warnings cover low blood counts, infection risk, non-melanoma skin cancer, raised lipids, major heart events, blood clots, and second cancers.

One warning follows from how the drug works. Stopping it suddenly can bring symptoms back fast and hard, because the signal being suppressed is still there. The label says to taper gradually. That is a decision for a clinician.

What this does not mean

• Ruxolitinib controls these diseases. It does not cure them, and it does not clear the mutated cells.
• An approval describes a group. Whether any of the four uses fits one person depends on the diagnosis, past treatments, and blood counts.
• Approval dates say when an option became available in the United States. Coverage, cost, and access are separate questions.
• The spleen-size and response-rate endpoints behind these approvals are not survival results. No trial here showed people living longer.
• This page is about the drug's US label. Rules elsewhere differ.

When to get checked

Myelofibrosis and polycythemia vera build slowly, and many people are found through a routine blood count. Ask a clinician about any of these:

• A full or aching feeling under the left ribs, or feeling full after a few mouthfuls
• Drenching night sweats, or itching that gets worse after a hot bath
• Bone or muscle pain that does not track with activity
• Unexplained bruising, nosebleeds, or bleeding gums
• Losing weight without trying, or fatigue that rest does not fix
• A blood count showing a high hematocrit, or platelets outside the normal range, on more than one test

For anyone already taking this drug, the label ties dosing to platelet counts, so regular blood tests are part of the treatment rather than an extra.

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• Drugs@FDA approval history, NDA 202192 (JAKAFI/ruxolitinib) (official)
• FDA prescribing information: JAKAFI (ruxolitinib) tablets, September 2021 (official)
• NCI drug information: Ruxolitinib Phosphate (official)
• FDA approval letter, NDA 202192 (JAKAFI), November 16, 2011 (official)
• DailyMed label: JAKAFI (ruxolitinib) tablets and JAKAFI XR extended-release tablets (official)

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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