Narrator: Dosing of Jakafi^® (ruxolitinib) in patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

Narrator: Jakafi (ruxolitinib) is indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.

Dr Erba: Hello, my name is Harry Erba. I'm a professor of internal medicine at the University of Alabama at Birmingham where I serve as the director of the hematologic malignancies program as well as the associate director of the cancer center for clinical research. For the last 20 years, I've been a clinical investigator evaluating novel therapies for people with myeloid neoplasms including the myeloproliferative neoplasms.

Narrator: This promotional presentation is being sponsored by Incyte Corporation.

Dr Erba: The information that I will present is all consistent with the labeled indication and consistent with FDA regulations. We will also discuss important safety information regarding Jakafi.

Dr Erba: Now let's discuss the appropriate dosing of Jakafi in patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

The starting dose of Jakafi in this patient population is 10 mg twice daily. Now remember the drug is potentially myelosuppressive and so blood counts should be checked frequently at first, every two to four weeks, and as they stabilize as clinically indicated. Also remember that the dose of Jakafi should be adjusted based on tolerability and the goals of your therapy.

Dr Erba: Although the starting dose of Jakafi is 10 mg twice daily, remember it's important to optimize the dose of Jakafi to these patients. In the RESPONSE trial in the first eight weeks, 9% of patients required a dose reduction. But it’s also important to remember that 37% of patients in the first eight weeks actually had a dose increase of Jakafi in an effort to actually achieve the goals of therapy.

Dr Erba: Remember as well that Jakafi is cleared by renal-hepatic mechanisms and so patients with renal-hepatic insufficiency should be considered for lower starting doses of Jakafi. Jakafi is metabolized by CYP3A4 and so patients on CYP3A4 inhibitors, strong ones or even the moderately strong CYP3A4 inhibitor fluconazole, should have a lower starting dose if the CYP3A4 inhibitor cannot be stopped.

Dr Erba: The prescribing information for polycythemia vera indicates that you should consider dose reductions of Jakafi based on platelet counts and hemoglobin.

Dr Erba: And this should be followed so as to attempt to avoid abrupt discontinuation for a hemoglobin less than eight or a platelet count less than 50,000.

Dr Erba: Why would we consider increasing the dose of Jakafi? Well remember in patients who are being treated with Jakafi, we're trying to achieve certain goals.

Dr Erba: The dose of Jakafi can be increased in 5 mg twice-daily increments. The maximum dose of Jakafi is 25 mg twice daily.

A dose adjustment or dose increase should not be done in the first four weeks and no sooner than every two weeks.

Dr Erba: I would consider a dose increase for my patients up to the maximum dose of 25 mg twice daily if they require and continue to require phlebotomy, if they still have leukocytosis, thrombocytosis, or splenomegaly.

Dr Erba: As long as they have appropriate marrow reserve and so their hemoglobin isn't low and their platelets and neutrophils can tolerate a higher dose.

Dr Erba: But remember if the patient has cytopenias you should not go up on the dose. And so in patients who have low ANC or low platelet count this will keep us from going up on the dose in those situations.

A dose adjustment or dose increase should not be done in the first four weeks and no sooner than every two weeks.

Narrator: Important Safety Information

• Treatment with Jakafi^® (ruxolitinib) can cause thrombocytopenia, anemia and neutropenia, which are each dose-related effects. Perform a pre-treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated
• Manage thrombocytopenia by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary
• Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi
• Severe neutropenia (ANC <0.5 × 10⁹/L) was generally reversible by withholding Jakafi until recovery
• Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting Jakafi until active serious infections have resolved. Observe patients receiving Jakafi for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines
• Tuberculosis (TB) infection has been reported. Observe patients taking Jakafi for signs and symptoms of active TB and manage promptly. Prior to initiating Jakafi, evaluate patients for TB risk factors and test those at higher risk for latent infection. Consult a physician with expertise in the treatment of TB before starting Jakafi in patients with evidence of active or latent TB. Continuation of Jakafi during treatment of active TB should be based on the overall risk-benefit determination
• Progressive multifocal leukoencephalopathy (PML) has occurred with Jakafi treatment. If PML is suspected, stop Jakafi and evaluate
• Herpes zoster infection has been reported in patients receiving Jakafi. Advise patients about early signs and symptoms of herpes zoster and to seek early treatment. Herpes simplex virus reactivation and/or dissemination has been reported in patients receiving Jakafi. Monitor patients for the development of herpes simplex infections. If a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment with Jakafi; patients should be promptly treated and monitored according to clinical guidelines
• Increases in hepatitis B viral load with or without associated elevations in alanine aminotransferase and aspartate aminotransferase have been reported in patients with chronic hepatitis B virus (HBV) infections. Monitor and treat patients with chronic HBV infection according to clinical guidelines
• When discontinuing Jakafi, myeloproliferative neoplasm-related symptoms may return within one week. After discontinuation, some patients with myelofibrosis have experienced fever, respiratory distress, hypotension, DIC, or multi-organ failure. If any of these occur after discontinuation or while tapering Jakafi, evaluate and treat any intercurrent illness and consider restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafi without consulting their physician. When discontinuing or interrupting Jakafi for reasons other than thrombocytopenia or neutropenia, consider gradual tapering rather than abrupt discontinuation
• Non-melanoma skin cancers (NMSC) including basal cell, squamous cell, and Merkel cell carcinoma have occurred. Perform periodic skin examinations
• Treatment with Jakafi has been associated with increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Assess lipid parameters 8-12 weeks after initiating Jakafi. Monitor and treat according to clinical guidelines for the management of hyperlipidemia
• Another JAK-inhibitor has increased the risk of major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and stroke (compared to those treated with tumor TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Jakafi 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 (DVT), pulmonary embolism (PE), and arterial thrombosis (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. In patients with myelofibrosis (MF) and polycythemia vera (PV) treated with Jakafi in clinical trials, the rates of thromboembolic events were similar in Jakafi and control treated patients. Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately
• Another JAK-inhibitor has increased the risk of lymphoma and other malignancies excluding NMSC (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi 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 Jakafi, particularly in patients with a known secondary malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers
• In myelofibrosis and polycythemia vera, the most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache, and diarrhea. In acute graft-versus-host disease, the most common nonhematologic adverse reactions (incidence >50%) were infections (pathogen not specified) and edema. In chronic graft-versus-host disease, the most common nonhematologic adverse reactions (incidence >20%) were infections (pathogen not specified) and viral infections
• Avoid concomitant use with fluconazole doses greater than 200 mg. Dose modifications may be required when administering Jakafi with fluconazole doses of 200 mg or less, or with strong CYP3A4 inhibitors, or in patients with renal or hepatic impairment. Patients should be closely monitored and the dose titrated based on safety and efficacy
• Use of Jakafi during pregnancy is not recommended and should only be used if the potential benefit justifies the potential risk to the fetus. Women taking Jakafi should not breastfeed during treatment and for 2 weeks after the final dose

Please see Full Prescribing Information for Jakafi.

Dr Erba: Thank you for listening and watching this presentation on the appropriate dosing of Jakafi for patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.