BMS Updates Safety Label for Inrebic

Bristol Myers Squibb has updated the warnings and precautions section of the labeling of Inrebic (fedratinib) to include information related to the safety of the JAK inhibitor class of therapies. Inrebc is an oral kinase inhibitor with activity against JAK2 and is used to treat patients with myelofibrosis, a type of bone marrow cancer.

Myelofibrosis is a serious and rare disorder that disrupts the body’s normal production of blood cells. Bone marrow is gradually replaced with fibrous scar tissue, which limits the ability of the bone marrow to make blood cells.

The newly added sections address the risk of major adverse cardiac events, thrombosis, and secondary malignancies that have been identified by studies of other JAK inhibitors that are used to treat arthritis and other inflammatory conditions.

In September 2021, the FDA required that the JAK inhibitors used to treat arthritis include revisions to the boxed warning section about the risk of serious heart-related events, cancer, blood clots, and death. Products required to make these changes included: Pfizer’s Xeljanz (tofacitinib), Eli Lilly’s Olumiant (baricitinib) and AbbVie’s Rinvoq (upadacitinib). The agency recommended that these therapies be reserved for patients who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.

At the time, the FDA said that two other JAK inhibitors, Novartis’ Jakafi (ruxolitinib) and Inrebic, were not subject to the requirement because they are not indicated to treat arthritis and other inflammatory conditions.

The regulatory agency made this requirement as a result of data released in January 2021 from a postmarketing cardiovascular safety trial of Xeljanz that found there was a higher risk of these events.

A BMS spokesperson said that even though the mechanism of action of Inrebic differs in its specificity from the other JAK inhibitors, the regulatory agency recommended it “should be treated as JAK inhibitor class-wide safety update to the prescribing information. Based on this assessment, BMS agreed to add the recommended class labeling language under the warnings and precautions portion of the Inrebic label calling out the occurrence with another JAK inhibitor, but not under its adverse drug reactions section,” the spokesperson said.

The newly added section to Inrebic’s labeling now reads:

5.6 Major Adverse Cardiac Events (MACE)

Another JAK-inhibitor has increased the risk of MACE, including cardiovascular death, myocardial infarction, and stroke (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Inrebic is not indicated.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Inrebic, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors.

Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.

Another JAK-inhibitor has increased the risk of thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Inrebic is not indicated. In patients with MF treated with Inrebic in clinical trials, the rates of thromboembolic events were similar in Inrebic and placebo treated patients.

Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately.

5.8 Secondary Malignancies

Another JAK-inhibitor has increased the risk of lymphoma and other malignancies excluding non-melanoma skin cancer (NMSC) (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Inrebic is not indicated. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Inrebic, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers.