Unable to view this email? Superior reductions in spleen volume and improvements in Total Symptom Score (TSS) vs placebo.1,2 Learn more at www.jakafi.com. JAK Pathway About Jakafi IncyteCARES Learn more > Jakafi®—the first and only FDA-approved agent for intermediate or high-risk myelofibrosis1,3 Dear Dr [Name], Consider Jakafi for your patients with intermediate or high-risk myelofibrosis. Jakafi reduces splenomegaly and improves the symptoms of myelofibrosis, as measured by TSS.* Symptoms measured by TSS were abdominal discomfort, early satiety, pain under left ribs, pruritus, night sweats and bone/muscle pain. In a clinical study, most patients receiving placebo experienced increased splenomegaly and worsening of symptoms.1,2 Jakafi regulates JAK1 and JAK2 signaling1,2 • Dysregulated Janus kinase (JAK) signaling is a key feature of myelofibrosis4 • Splenomegaly and debilitating symptoms of myelofibrosis have been linked to dysregulated JAK signaling5 • Dysregulated JAK signaling may occur via many mechanisms, including3,6-13 — JAK2 mutations — Receptor mutations (eg, MPL mutations) — Increased JAK1 signaling — Excess cytokines — Damaged intracellular signaling mechanisms (eg, those involving SOCS) View the Jakafi Mechanism of Action (MOA) video > MPL = myeloproliferative leukemia virus oncogene; SOCS = suppressor of cytokine signaling. • Treatment with Jakafi can cause hematologic adverse reactions, including thrombocytopenia, anemia and neutropenia, which are each dose-related effects, with the most frequent being thrombocytopenia and anemia • Patients should be assessed for the risk of developing serious bacterial, mycobacterial, fungal and viral infections • The three most frequent non-hematologic adverse reactions were bruising, dizziness and headache Jakafi demonstrated superior reductions in spleen volume and significant improvements in symptom scores1,14,15 41.9% vs 0.7%1,2† Patients achieving a >35% reduction in spleen volume at 24 weeks vs placebo (COMFORT-I) (P < 0.0001) 28.5% vs 0%1,2‡ Patients achieving a >35% reduction in spleen volume at 48 weeks vs best available therapy (BAT) (COMFORT-II) (P < 0.0001) 45.9% vs 5.3%1,2† Patients achieving a >50% improvement in TSS at 24 weeks vs placebo (COMFORT-I) (P < 0.0001) Reductions in spleen volume and improvements in TSS were seen with Jakafi in both JAK2V617F-positive and JAK2V617F-negative patients, relative to placebo.2 Each bar represents an individual patient's response. Each bar represents an individual patient's response. Worsening of TSS is truncated at 150%. Please see Important Safety Information. Learn more about how Jakafi can help your patients >   * TSS was captured by the modified Myelofibrosis Symptom Assessment Form (MFSAF v2.0), a daily patient diary recorded for 25 weeks. Symptom scores ranged from 0 to 10 with 0 representing symptoms "absent" and 10 representing "worst imaginable" symptoms. These scores were added to create the daily total score, which has a maximum of 60. At baseline, mean TSS was 18.0 in the group receiving Jakafi and 16.5 in the placebo group.1,2 † Based on COMFORT-I, a randomized, double-blind, placebo-controlled study in patients with myelofibrosis who were refractory to or not candidates for available therapy.1,14 ‡ Based on COMFORT-II, an open-label, randomized study of Jakafi vs BAT.1,15   IncyteCARES (Connecting to Access, Reimbursement, Education and Support) IncyteCARES offers free educational support for your patients taking Jakafi. Order the IncyteCARES Patient Starter Packet > Learn about Jakafi View the Jakafi MOA video and learn about how Jakafi works. Order the IncyteCARES Patient Starter Packet Give your patients this resource, which provides information about Jakafi treatment and patient support services. Sign up for more information Stay current with the latest news and information about Jakafi. Indications and Usage Jakafi is indicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis and post–essential thrombocythemia myelofibrosis. Important Safety Information • Treatment with Jakafi can cause hematologic adverse reactions, including thrombocytopenia, anemia and neutropenia, which are each dose-related effects, with the most frequent being thrombocytopenia and anemia. A complete blood count must be performed before initiating therapy with Jakafi. Complete blood counts should be monitored as clinically indicated and dosing adjusted as required • The three most frequent non-hematologic adverse reactions were bruising, dizziness and headache • Patients with platelet counts <200 x 109/L at the start of therapy are more likely to develop thrombocytopenia during treatment. Thrombocytopenia was generally reversible and was usually managed by reducing the dose or temporarily withholding Jakafi. If clinically indicated, platelet transfusions may be administered • Patients developing anemia may require blood transfusions. Dose modifications of Jakafi for patients developing anemia may also be considered • Neutropenia (ANC <0.5 x 109/L) was generally reversible and was managed by temporarily withholding Jakafi • Patients should be assessed for the risk of developing serious bacterial, mycobacterial, fungal and viral infections. Active serious infections should have resolved before starting Jakafi. Physicians should carefully observe patients receiving Jakafi for signs and symptoms of infection (including herpes zoster) and initiate appropriate treatment promptly • A dose modification is recommended when administering Jakafi with strong CYP3A4 inhibitors or in patients with renal or hepatic impairment [see Dosage and Administration]. Patients should be closely monitored and the dose titrated based on safety and efficacy • There are no adequate and well-controlled studies of Jakafi in pregnant women. 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 breast-feed. Discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother Please see Full Prescribing Information. References: 1. Jakafi Prescribing Information. Incyte Corporation. November 2011. 2. Data on file. Incyte Corporation. 3. Quintás-Cardama A, Vaddi K, Liu P, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2010;115:3109-3117. 4. Anand S, Stedham F, Gudgin E, et al. Increased basal intracellular signaling patterns do not correlate with JAK2 genotype in human myeloproliferative neoplasms. Blood. 2011;118:1610-1621. 5. Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010;363:1117-1127. 6. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779-1790. 7. Levine RL, Pardanani A, Tefferi A, Gilliland DG. Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat Rev Cancer. 2007;7:673-683. 8. Scott LM, Tong W, Levine RL, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007;356:459-468. 9. Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3:1140-1151. 10. Kralovics R. Genetic complexity of myeloproliferative neoplasms. Leukemia. 2008;22:1841-1848. 11. Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A. Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol. 2011;29:1356-1363. 12. Verstovsek S. Therapeutic potential of JAK2 inhibitors. Hematology Am Soc Hematol Educ Program. 2009:636-642. 13. Fourouclas N, Li J, Gilby DC, et al. Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in myeloproliferative disorders. Haematologica. 2008;93:1635-1644. 14. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366:799-807. 15. Harrison C, Kiladjian J-J, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366:787-798.     Jakafi is a registered trademark of Incyte Corporation. © 2012, Incyte Corporation. All rights reserved. RUX-1127c 06/12 Incyte Corporation P.O. Box 4689 Trenton, NJ 08650 Replies to the email address do-not-reply@incyte.com will not be processed. For more information, please contact us at 1-855-4-Jakafi (855-452-5234).