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Favorable Response Rates Suggest Promise of Ibrutinib (IMBRUVICAÂ®) Combination Therapy in Two Common Types of Non-Hodgkin’s Lymphoma

On December 4, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported encouraging efficacy and safety findings from two separate studies evaluating ibrutinib (IMBRUVICA) as a combination therapy in two of the most common types of non-Hodgkin’s lymphoma: diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) (Press release, AbbVie, DEC 4, 2016, View Source [SID1234516911]). IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

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In a Phase 1b study of patients with relapsed/refractory (R/R) DLBCL, the investigational combination of ibrutinib, rituximab, and escalating doses of lenalidomide were tested (abstract #473). Preliminary efficacy results demonstrated the highest response rate was observed in patients with the worst prognosis subtype (non-GCB) and in patients with transformed disease.1 These data will be presented today in an oral presentation at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, CA.

"Though standard therapy can cure over half of patients with diffuse large B-cell lymphoma (the most common form of aggressive lymphoma), patients with relapsed or refractory disease do overall poorly with only less than a quarter of patients efficiently salvaged with current strategies including stem cell transplantation," said Andre Goy, M.D., Chairman and Executive Director at John Theurer Cancer Center at Hackensack University Medical Center in New Jersey and lead investigator of the study.* "We are encouraged by these results in a heavily pretreated and refractory population and look forward to further evaluating the efficacy of ibrutinib combination therapy with rituximab and lenalidomide in the Phase 2 portion of the study."

Separately at the meeting, data from a Phase 2 multicenter study showed that the combination of ibrutinib and rituximab produced favorable response rates in patients with previously untreated FL (abstract #1804). At a median time on study of 22 months, the overall response rate (ORR) was 85%, with 35% of patients achieving a complete response (CR).2 The data were presented in a poster presentation on Saturday, December 3.

"We are highly encouraged by this longer-term data showing strong and durable responses that appear to improve with an extended treatment duration," said Nathan Fowler, M.D., Associate Professor, Department of Lymphoma/Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX and lead investigator of the study.* "The results of the study to date suggest that the addition of ibrutinib to rituximab in the front-line follicular lymphoma setting provides enhanced outcomes over rituximab alone."

DLCBL is an aggressive B-cell lymphoma and the most common subtype of non-Hodgkin’s lymphoma. Despite 50-60% of patients being cured with standard chemo-immunotherapy, patients who relapse have poor outcomes.3 FL is the most common subtype of indolent non-Hodgkin’s lymphoma. It is often slow-growing, but is considered incurable in advanced stages. Over time, about one-third of FL cases advance to the fast-growing DLBCL.4

"The response rates observed with ibrutinib combination therapy in treatment-naïve follicular lymphoma and relapsed/refractory diffuse large B-cell lymphoma show promise for patients with two different types of non-Hodgkin’s lymphoma," said Darrin Beaupre, M.D., Ph.D., Head of Early Development and Immunotherapy at Pharmacyclics LLC, an AbbVie company. "We pioneered the development of BTK inhibition with ibrutinib, and we continue to progress our robust development program. Based on the encouraging Phase 2 study results in FL, we are initiating a Phase 3 study of the combination of ibrutinib and rituximab in the first-line setting."

About the Studies

Abstract #473: A multicenter, open-label phase 1b/2 study of ibrutinib in combination with lenalidomide and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (Oral Presentation; Sunday, December 4, 4:30 PM PT)

Subjects with R/R DLBCL were treated with the investigational combination of ibrutinib 560 mg once daily, rituximab 375 mg/m2 on day one for six cycles and escalating doses of lenalidomide. Preliminary data for 45 patients showed responses on 15 mg, 20 mg, and 25 mg lenalidomide, with responses for patients with the non-GCB subtype (response-evaluable population) seen in more than half of the subjects. Patients with transformed disease also showed favorable responses. Overall, the treatment combination was tolerable. The most frequent Grade 3 or 4 adverse events (AEs) were neutropenia (38%), thrombocytopenia (11%), and maculopapular rash (11%). Based on safety data from this portion of the study, the Phase 2 portion of the trial is being initiated.1

Abstract #1804: Ibrutinib combined with rituximab in treatment-naïve patients with follicular lymphoma: Arm 1 + arm 2 results from a multicenter, open-label phase 2 study (Poster Presentation; Saturday, December 3, 5:30 PM – 7:30 PM PT)

Updated data were presented for 80 patients with FL receiving two different administration schedules of ibrutinib and rituximab (Arm 1, 60 patients; Arm 2, 20 patients). In Arm 1 at a median time on study of 22 months, the ORR was 85%, with 35% CR. Median time to best response was 2.7 months. With a median time on study of 15 months in Arm 2, ORR was 75%, with 35% CR. Median time to best response was 4.3 months. Median duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were not reached in either arm.2

In Arm 1, patients received ibrutinib 560 mg once daily until disease progression or unacceptable toxicity and rituximab 375 mg/m2 once weekly for four weeks. In Arm 2, patients received ibrutinib 560 mg once daily for eight weeks, then concurrent rituximab once weekly for four weeks, followed by ibrutinib 560 mg once daily until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed ORR. Secondary endpoints included DOR, PFS and OS.2

Treatment was well tolerated, with no new safety signals with longer follow up. AEs were primarily Grade 1 or 2. The most common AEs included fatigue (68%), diarrhea (52%), nausea (47%), headache (30%), cough, myalgia, maculopapular rash (28% each), and muscle spasms (23%) in Arm 1, and fatigue (80%), diarrhea (60%), nausea (55%), myalgia (45%), maculopapular rash (35%), and headache, cough and muscle spasms (25% each) in Arm 2. Common Grade 3 or 4 AEs in either Arm 1 or 2 included maculopapular rash (5% and 10%, respectively), fatigue (7% and 5%), pyrexia (3% and 10%) and diarrhea (2% and 10%).2

About IMBRUVICA
IMBRUVICA is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.5,6 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.5

IMBRUVICA is approved to treat patients with CLL/SLL including patients with 17p deletion, patients with mantle cell lymphoma who have received at least one prior therapy and patients with Waldenström’s macroglobulinemia. Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.5

IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry with nearly 30 (n=27) company-sponsored trials underway, 14 of which are Phase 3. In addition, there are more than 40 (n=44) investigator-sponsored trials taking place around the world. To date, more than 65,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage – Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.

Infections – Fatal and nonfatal infections have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA. Evaluate patients for fever and infections and treat appropriately.

Cytopenias – Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 9%) based on laboratory measurements occurred in patients treated with single agent IMBRUVICA. Monitor complete blood counts monthly.

Atrial Fibrillation – Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.

Hypertension – Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.

Second Primary Malignancies – Other malignancies (range, 5% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4% to 13%).

Tumor Lysis Syndrome – Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity – Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS

The most common adverse reactions (?20%) in patients with B-cell malignancies (MCL, CLL/SLL, and WM) were neutropenia** (64%), thrombocytopenia** (63%), diarrhea (43%), anemia** (41%), musculoskeletal pain (30%), rash (29%), nausea (29%), bruising (29%), fatigue (27%), hemorrhage (21%), and pyrexia (21%).

**Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).

The most common Grade 3 or 4 non-hematologic adverse reactions (?5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

Approximately 6% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse reactions.

Approximately 4%-10% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse reactions. Most frequent adverse reactions leading to discontinuation were pneumonia, hemorrhage, atrial fibrillation, rash and neutropenia (1% each) in CLL patients and subdural hematoma (1.8%) in MCL patients.

DRUG INTERACTIONS

CYP3A Inhibitors – Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.

CYP3A Inducers – Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment – Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA dose.

Please see Full Prescribing Information: View Source

Kite Pharma Initiates Rolling Submission of U.S. Biologics License Application (BLA) for KTE-C19, its Investigational anti-CD19 CAR-T Therapy, for the Treatment of Patients with Relapsed/Refractory Aggressive B-cell Non-Hodgkin Lymphoma (NHL)

On December 4, 2016 Kite Pharma, Inc. (Nasdaq:KITE) reported that it has initiated the rolling submission with the U.S. Food and Drug Administration (FDA) of the Biologics License Application (BLA) for KTE-C19 as a treatment for patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant (ASCT) (Press release, Kite Pharma, DEC 4, 2016, View Source [SID1234516910]). The pivotal ZUMA-1 study supporting this submission enrolled patients with chemorefractory diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL), three subtypes of aggressive NHL. The company expects to complete its BLA submission by the end of the first quarter of 2017.

"I am both proud and appreciative of the Kite team and our clinical investigators, who have helped to make this key milestone possible," said Arie Belldegrun, M.D., FACS, Chairman, President, and Chief Executive Officer of Kite. "This is an important first step toward Kite’s biggest goal – bringing to market a potentially life-saving treatment for patients suffering from aggressive NHL."

Kite also announced that the United States Adopted Name, or USAN, for KTE-C19 will be axicabtagene ciloleucel.

Axicabtagene ciloleucel (KTE-C19) received Breakthrough Therapy Designation (BTD) by the FDA in December 2015. If approved, Kite plans to commercially launch KTE-C19 in 2017. Kite is also planning a regulatory submission to the European Medicines Agency (EMA) for axicabtagene ciloleucel in 2017. Kite was granted access to Priority Medicines (PRIME) regulatory support in 2016 by the EMA for axicabtagene ciloleucel (KTE-C19) for the treatment of refractory DLBCL.

About axicabtagene ciloleucel

Kite Pharma’s lead product candidate, axicabtagene ciloleucel, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. Axicabtagene ciloleucel has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.

Kite Pharma Reports 82 Percent of Patients Achieved Complete Remission in Preliminary Analysis from Phase 1 ZUMA-3 and ZUMA-4 Trials of KTE-C19 in Adult and Pediatric Patients with High Burden Relapsed/Refractory Acute Lymphoblastic Leukemia

On December 4, 2016 Kite Pharma, Inc. (Nasdaq:KITE) reported that 82 percent of patients (9 out of 11) achieved complete remission or complete remission with incomplete or partial hematological recovery in a preliminary analysis of the Phase 1 ZUMA-3 and ZUMA-4 trials of KTE-C19 in adult and pediatric relapsed/refractory acute lymphoblastic leukemia (r/r ALL) (Press release, Kite Pharma, DEC 4, 2016, View Source [SID1234516909]). In these patients, 100 percent of responders tested negative for minimal residual disease (MRD), which has been shown to correlate with risk of disease relapse in ALL. The data were presented today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, CA.

In the Phase 1 trials, 13 patients were treated with KTE-C19. Eleven patients were evaluable for response and two patients have not reached the evaluation time point at the data cutoff. Patients received a low-dose conditioning chemotherapy regimen based on extensive clinical experience at the National Cancer Institute (NCI).

"We are encouraged by the KTE-C19 safety and efficacy profile in ALL that is suggested by these data," said David Chang M.D., Ph.D., Executive Vice President, Research and Development, and Chief Medical Officer of Kite. "In the Phase 1 portion of these studies, we are enrolling patients with high disease burden to rigorously evaluate safety and efficacy of KTE-C19. We look forward to initiating the Phase 2 portions of these studies in 2017."

Five of 13 (38 percent) patients had ≥ grade 3 cytokine release syndrome (CRS) and five of 13 (38 percent) had ≥ grade 3 neurological events. One patient in ZUMA-3 died from KTE-C19 related CRS and one patient in ZUMA-4 died from a disseminated fungal infection unrelated to KTE-C19. No cerebral edema has been observed.

KTE-C19 was successfully manufactured in these 13 patients across a range of absolute lymphocyte and blast counts in a centralized and streamlined process of six to eight days. The KTE-C19 manufacturing process used in the multicenter ZUMA-3 and ZUMA-4 studies will be discussed in an oral presentation on Monday, December 5, 2016, at 6:45 p.m. PST.

Production of Anti-CD19 CAR T Cells for ZUMA-3 and -4: Phase 1/2 Multicenter Studies Evaluating KTE-C19 in Patients with Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (R/R ALL)

Abstract #1227 View Source
Presenter: Marianna Sabatino, M.D., Kite Pharma, Director of Product Sciences

About KTE-C19

Kite Pharma’s lead product candidate, KTE-C19, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. KTE-C19 has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.

Further clinical data for lirilumab and IPH4102 presented at ASH annual meeting reinforcing confidence in our programs

On December 5, 2016 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that clinical data for lirilumab and IPH4102 were presented in two posters at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s (ASH) (Free ASH Whitepaper) 2016 Annual Meeting (December 3-6, 2016), San Diego, CA, U.S.:

Poster 1826 entitled "First-in-Human, Multicenter Phase I Study of IPH4102, First-in-Class Humanized Anti-KIR3DL2 Monoclonal Antibody, in Relapsed/Refractory Cutaneous T-Cell Lymphomas: Preliminary Safety, Exploratory and Clinical Activity Results" was presented by Prof. Y. Kim from the Stanford Cancer Institute and investigator of the study(Press release, Innate Pharma, DEC 4, 2016, View Source [SID1234516908]). IPH4102 is Innate Pharma’s wholly-owned first-in-class anti-KIR3DL2 antibody.
This poster presented preliminary results from the first seven dose levels of the dose-escalation part of the Phase I trial of IPH4102 (1). They showed that the drug candidate is well tolerated in patients with relapsed/refractory CTCL (2) and a preliminary global objective response rate (ORR) of 38% in the evaluable population across all dosage levels.

Explorative assessments show that clinical improvement in skin comes along with decreases of malignant cells and normalization of immune parameters in the tumor microenvironment. All responses were ongoing at the time of poster presentation.

Dose level 8 (3 mg/kg) has been completed without dose-limiting toxicity. Two further dose levels (6 and 10 mg/kg) remain to be explored in the dose-escalation part of this study.

Poster 1641 entitled "Phase IB/II Study of Lirilumab in Combination with Azacytidine in Patients with Relapsed Acute Myeloid Leukemia" was presented by Dr N. Daver from the Department of Leukemia at the MD Anderson Cancer Center.
Lirilumab is a first-in-class fully human monoclonal antibody that blocks inhibitory killer-cell immunoglobulin-like receptors (KIRs) expressed predominantly on natural killer (NK) cells to potentiate an anti-tumor immune response mediated by the latter. Lirilumab is licensed to Bristol-Myers Squibb Company by Innate Pharma.

In this Phase Ib/II study testing lirilumab in combination with azacytidine in a heavily pretreated patient population with relapsed AML, full doses of azacytidine and lirilumab (3) were well tolerated. No dose-limiting toxicities were observed. Preliminary efficacy data for 25 evaluable patients showed a response rate of 20% including two patients achieved a CR (4) or a CR with insufficient count recovery and three achieving hematologic improvement.

"Preliminary results presented at ASH (Free ASH Whitepaper) 2016 are encouraging, as they further reinforce the favorable safety profile of both lirilumab and IPH4102. The study of IPH4102 conducted in patients with CTCL is progressing very well and we look forward to the completion of the dose-escalation part of the trial to confirm the encouraging efficacy signal seen across dose levels to date," said Pierre Dodion, Chief Medical Officer of Innate Pharma. "The good safety profile of lirilumab in combination with azacytidine in patients with relapsed AML further supports the view that lirilumab is well tolerated in numerous combinations."

Posters Details

IPH4102

Poster title: "First-in-Human, Multicenter Phase I Study of IPH4102, First-in-Class Humanized Anti-KIR3DL2 Monoclonal Antibody, in Relapsed/Refractory Cutaneous T-Cell Lymphomas: Preliminary Safety, Exploratory and Clinical Activity Results"
Date: Saturday, December 3, 2016
Time: 5:30 p.m. – 7:30 p.m. PST
Presenter: Pr Youn Kim, Division of Oncology, Department of Medicine, Stanford Cancer Institute, Palo Alto, CA, U.S
Location: Hall GH, San Diego Convention Center, San Diego, CA, U.S.
The poster #1826 is available on Innate Pharma’s website.

Lirilumab

Poster title: "Phase IB/II Study of Lirilumab in Combination with Azacytidine (AZA) in Patients (pts) with Relapsed Acute Myeloid Leukemia (AML)"
Date: Saturday, December 3, 2016
Time: 5:30 p.m. – 7:30 p.m. PST
Presenter: Dr Naval Daver, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.
Location: Hall GH, San Diego Convention Center, San Diego, CA, U.S.
The poster #1641 will be soon available on Innate Pharma’s website.

Pooled Analysis of Five-Year Data from Two Phase 3 Studies Further Supports Overall Survival Advantage Observed in Patients with Myelofibrosis Treated With Jakafi® (ruxolitinib)

On December 4, 2016 Incyte Corporation (Nasdaq:INCY) reported an exploratory pooled analysis of data from the five-year follow-up of the Phase 3 COMFORT-I and COMFORT-II trials which further supports previously published overall survival findings and suggests that earlier treatment with Jakafi (ruxolitinib) may result in an improved survival advantage for patients with intermediate-2 or high-risk myelofibrosis (MF) than best available therapy (BAT) or placebo (Press release, Incyte, DEC 4, 2016, View Source;p=RssLanding&cat=news&id=2227338 [SID1234516907]). These data also reinforce previous long-term results observed with ruxolitinib compared with controls (BAT or placebo).

"Understanding how earlier treatment with Jakafi may impact overall survival for appropriate patients with myelofibrosis is critical as physicians look to identify the most effective treatment approach for patients with this rare and debilitating disease," said Peg Squier, M.D., Ph.D., Incyte’s Head of U.S. Medical Affairs.

The 5-year, intent-to-treat analysis of pooled data from two Phase 3 studies showed prolonged survival for patients with intermediate-2 or high-risk MF randomized to ruxolitinib, with the risk of death reduced by 30 percent for patients who received ruxolitinib compared with the control groups. Ruxolitinib also exhibited an overall survival (OS) advantage in various patient subgroup analyses including age, sex, disease type, risk status, JAK2V617F mutation status, baseline spleen length, anemia, white blood cell count, and platelet count. Additionally, using data-modeling techniques aimed at correcting for crossover delay, overall survival advantage was more pronounced for patients who were randomized to receive ruxolitinib at the start of the trial compared with patients who crossed over from control to ruxolitinib.

These data are scheduled for presentation today at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2016 taking place in San Diego, California.

Results from the COMFORT-I & COMFORT-II Pooled Analysis
The double-blind COMFORT-I trial and the open-label COMFORT-II trial were both randomized Phase 3 studies that evaluated the safety and efficacy of ruxolitinib in 528 patients with intermediate-2 or high-risk primary MF, post–polycythemia vera MF, or post–essential thrombocythemia MF. Across the pooled analysis, there were a total of 301 patients randomized to ruxolitinib (COMFORT-I, n=155; COMFORT-II, n=146), 227 to placebo in COMFORT-I (n=154) or to BAT in COMFORT-II (n=73).

In both COMFORT-I and COMFORT-II, patients were permitted to cross over to ruxolitinib from control treatment if they had progressive splenomegaly or a protocol-defined progression event. Crossover was mandatory following treatment unblinding in COMFORT 1. All continuing patients in the control arm in COMFORT II crossed over to ruxolitinib by the 3 year follow-up.

At the five-year intent-to-treat analysis, 42.5 percent (n=128) of the patients randomized to the ruxolitinib group died compared with 51.5 percent (n=117) of the patients randomized to the control group. Key findings include the following results:
Median overall survival for ruxolitinib was 5.3 years compared with 3.8 years for the control group.

Using a rank-preserving structural failure time modeling method, the OS advantage was more pronounced for patients originally randomized to ruxolitinib compared with patients who crossed over from control to ruxolitinib (median OS: ruxolitinib, 5.3 y; control, 2.3 y; HR, 0.35; 95% CI, 0.23–0.59), which suggests that the delay in ruxolitinib treatment may be the underlying reason for the difference in survival.

This analysis (Abstract #3110) is being presented as a part of a poster session (#634) on Sunday, December 4, 2016, 6:00-8:00 PM PST, Hall GH.

About Myelofibrosis (MF)
MF is part of a group of related rare blood cancers known as myeloproliferative neoplasms (MPNs). In MF, a patient’s bone marrow can no longer produce enough normal blood cells, causing the spleen and or liver to enlarge.1 MF is a progressive disease, which leads to bone marrow scarring and significant debilitating disease-related symptoms such as anemia, fatigue, and itching which can result in a poor quality of life.2 Patients with MF have a decreased life expectancy, with an average survival of approximately five to six years.3 The cause of MF is unknown but is linked to genetic mutations—between 50% and 60% of people with MF have a specific mutation of the Janus Kinase 2 gene (JAK2).4

About Jakafi (ruxolitinib)
Jakafi is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. Food and Drug Administration, for treatment of people with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF, and post–essential thrombocythemia MF.

Jakafi is also indicated for treatment of people with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi (ruxolitinib) outside the United States. Jakafi is a registered trademark of Incyte Corporation. Jakavi is a registered trademark of Novartis AG in countries outside the United States.

Important Safety Information
Jakafi can cause serious side effects, including:
Low blood counts: Jakafi (ruxolitinib) may cause your platelet, red blood cell, or white blood cell counts to be lowered. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will perform blood tests to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of
Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you develop or have worsening symptoms such as unusual bleeding, bruising, tiredness, shortness of breath, or a fever.

Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.
Skin cancers: Some people who take Jakafi have developed certain types of non-melanoma skin cancers. Tell your healthcare provider if you develop any new or changing skin lesions.

Increases in Cholesterol: You may have changes in your blood cholesterol levels. Your healthcare provider will do blood tests to check your cholesterol levels during your treatment with Jakafi.

The most common side effects of Jakafi include: low platelet count, low red blood cell counts, bruising, dizziness, headache.
These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Tell your healthcare provider about any side effect that bothers you or that does not go away.

Before taking Jakafi, tell your healthcare provider about: all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had tuberculosis (TB), or have been in close contact with someone who has TB, have or had hepatitis B, have or had liver or kidney problems, are on dialysis, had skin cancer or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change or stop taking Jakafi without first talking to your healthcare provider. Do not drink grapefruit juice while on Jakafi.

Women should not take Jakafi while pregnant or planning to become pregnant, or if breast-feeding.
Full Prescribing Information, which includes a more complete discussion of the risks associated with Jakafi, is available at www.jakafi.com.