Efficacy

Efficacy in uncontrolled polycythemia vera

Jakafi® (ruxolitinib) is the first and only FDA-approved treatment for patients with polycythemia vera who have had an inadequate response to or are intolerant of HU1

Approval based on evidence from the RESPONSE trial

  • RESPONSE was a randomized, open-label, active-controlled phase 3 trial comparing Jakafi with best available therapy (BAT) in 222 patients with PV1,2
  • 84% of patients crossed over to Jakafi between weeks 32 and 481

Strictly defined composite primary endpoint from the RESPONSE trial1,2:

Jakafi demonstrated superior results vs best available therapy1

  • A significantly larger proportion of patients in the Jakafi group achieved a response in hematocrit control as well as reduction in spleen volume compared with best available therapy at week 321
  • 77% of patients receiving Jakafi met at least one component of the primary response, compared with 20% of patients receiving best available therapy2

Patients with PV who had an inadequate response to or were intolerant of HU and received Jakafi achieved a consistent response over time1,2

Percent of patients achieving the primary and a key secondary endpoint1

  • 91% of patients who responded to Jakafi achieved a durable primary response, defined as maintaining that response at week 481

Jakafi helped achieve complete hematologic remission1

Key secondary endpoint from RESPONSE trial1

  • Proportion of patients achieving complete hematologic remission at week 32, defined as achieving hematocrit control, platelet count ≤400 x 109/L, and white blood cell count <10 x 109/L1

Efficacy in myelofibrosis

Efficacy in myelofibrosis demonstrated in COMFORT-I and COMFORT-II, the largest clinical programs in myelofibrosis to date.1,5,6

The efficacy and safety of Jakafi were evaluated in two clinical trials of patients with intermediate-2 or high-risk myelofibrosis.

  • COMFORT-I compared Jakafi to placebo1,5
  • COMFORT-II compared Jakafi to best available therapy (BAT)1,2,6

In COMFORT-I, Jakafi significantly improved intermediate or high-risk myelofibrosis-related symptoms and splenomegaly1,5

Superior to placebo at reducing spleen volume1,5

  • 42% of patients taking Jakafi achieved a ≥35% reduction in spleen volume at Week 24 vs 0.7% of patients taking placebo (P <0.0001)1,5

Superior to placebo at improving symptoms1,5

  • 46% of patients taking Jakafi achieved a ≥50% improvement in Total Symptom Score vs 5% of patients taking placebo (P <0.0001)1,5
  • Symptoms were measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 tool, a daily diary capturing the debilitating symptoms of myelofibrosis (abdominal discomfort, early satiety, pain under left ribs, pruritus, night sweats and bone/muscle pain), using a scale of 0 to 10, where 0 is absent and 10 is the worst imaginable1,8*

*These scores were added to create the daily total score, which has a maximum value of 60. At baseline, mean Total Symptom Score was 18.0 in the Jakafi group and 16.5 in the placebo group.

Chart shows the percent change in total symptom score in individual patients from baseline to week 24 or last observation.

Overall survival data from COMFORT-I1

COMFORT-I: At 3 years, survival probability for the population randomized to Jakafi was 70% and 61% for the population randomized to placebo.1

Overall survival was a secondary endpoint in COMFORT-I. Patients in the placebo group were eligible for crossover in the study, and the median time to crossover was 9 months.2

Chart shows the percent change in total symptom score in individual patients vs worsening with placebo from baseline at week 24.

Improvements were seen in all 6 of the individual symptoms that contributed to the Total Symptom Score—all measured symptoms worsened in patients taking placebo5,8

Reductions in spleen volume and improvements in Total Symptom Score were seen with Jakafi in both JAK2V617F-positive and JAK2V617F-negative patients, relative to placebo.5,8

Chart shows the percent change in total symptom score in individual patients vs worsening with placebo from baseline at week 24.

Additional analysis of COMFORT-I data showed that benefits of Jakafi were seen in patients with and without new onset anemia2,8

Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi. See below for related and other important safety information.

Chart shows the effects of grade 3 or 4 anemia  on spleen volume over time vs. tss over time.

Additional data from COMFORT-I show that patients with intermediate-2 or high-risk MF experienced similar reductions in spleen volume and improvements in Total Symptom Score independent of spleen size and Total Symptom Score at baseline5,9

Palpable spleen length from the costal margin ranged from 5–34 cm. Patients with the lowest observed palpable spleen length of 5 cm (n = 6) had a median spleen volume of 1073.5 cm3 (approximately 5 times the normal median spleen volume of 200 cm3).2,5,6

Patients with intermediate-1 risk myelofibrosis may have symptoms that require treatment.7

Chart shows the mean change in total symptom score from baseline.
Chart shows the  mean change in spleen volume from baseline.

COMFORT-II: A 48-week, phase 3 trial of Jakafi vs best available therapy1,6

  • 29% of patients receiving Jakafi achieved a ≥35% reduction in spleen volume at Week 48 vs 0% of patients receiving best available therapy (P <0.0001)1,6
  • Symptoms improved in patients taking Jakafi but worsened in those taking best available therapy, as measured by established scales of cancer symptom burden6

Overall survival data from COMFORT-II1

In COMFORT-II: At 3 years, survival probability for the population randomized to Jakafi was 79% and 59% for the population randomized to best available therapy (BAT).1

Overall survival was a secondary endpoint in COMFORT-II. Patients in the best available therapy (BAT) group were eligible for crossover, and the median time to crossover was 17 months.1

Expand References +
  • Jakafi Prescribing Information. Incyte Corporation.
  • Data on file, Incyte Corporation.
  • Barosi G, Birgegard G, Finazzi G, et al. Br J Haematol. 2009;148(6):961-96.
  • Spivak JL. Ann Intern Med. 2010;152(5):300-306.
  • Verstovsek S, Mesa RA, Gotlib J, et al. N Engl J Med. 2012;366:799-807. [also supplementary appendix: http://www.nejm.org/action/showSupplements?doi=10.1056%2FNEJMoa1110557&viewType=Popup&viewClass=Suppl]
  • Harrison C, Kiladjian JJ, Al-Ali HK, et al. N Engl J Med. 2012;366:787-798.
  • Deisseroth AB, Kaminskas E, Grillo J, et al. Clin Cancer Res. 2012;18:3212-3217.
  • Verstovsek S, Mesa RA, Gotlib J, et al. N Engl J Med. 2012;366(suppl):1-38.
  • Verstovsek S, Mesa RA, Gotlib J, et al. Br J Haematol. 2013;161:508-516.

INDICATIONS AND USAGE

Jakafi is indicated for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is indicated for treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF.

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 x 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
  • 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 ruxolitinib treatment for myelofibrosis. If PML is suspected, stop Jakafi and evaluate
  • Advise patients about early signs and symptoms of herpes zoster and to seek early treatment
  • 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 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
  • The three most frequent non‐hematologic adverse reactions (incidence >10%) were bruising, dizziness and headache
  • A dose modification is recommended when administering Jakafi with strong CYP3A4 inhibitors or fluconazole 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 breast‐feed

Please see Full Prescribing Information for Jakafi.

 
IMPORTANT SAFETY INFORMATION
 
INDICATIONS AND USAGE
Jakafi is indicated for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is indicated for treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF.
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 x 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
  • 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 ruxolitinib treatment for myelofibrosis. If PML is suspected, stop Jakafi and evaluate
  • Advise patients about early signs and symptoms of herpes zoster and to seek early treatment
  • 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 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
  • The three most frequent non‐hematologic adverse reactions (incidence >10%) were bruising, dizziness and headache
  • A dose modification is recommended when administering Jakafi with strong CYP3A4 inhibitors or fluconazole 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 breast‐feed

Please see Full Prescribing Information for Jakafi.