On June 10, 2016 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported that interim data were presented from a Phase 1/2 study of ALXN1210, an investigational, highly innovative longer-acting anti-C5 antibody, in patients with paroxysmal nocturnal hemoglobinuria (PNH), a debilitating, ultra-rare blood disorder characterized by complement-mediated hemolysis (destruction of red blood cells) (Press release, Alexion, JUN 10, 2016, View Source [SID:1234513201]).1 In this study, once-monthly dosing of ALXN1210 achieved rapid and sustained reductions in mean levels of lactate dehydrogenase (LDH), a marker of hemolysis, in 100 percent of treated patients, which were observed through up to five once-monthly dosing intervals. Researchers also reported that, at this time, 80 percent of patients who required at least 1 blood transfusion in the 12 months prior to treatment with ALXN1210 did not require transfusions while on treatment.2 These findings were presented in a late-breaking poster at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Copenhagen, Denmark.

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In a separate late-breaking poster at EHA (Free EHA Whitepaper), additional interim results were presented from a Phase 2 trial evaluating ALXN1007, a novel anti-inflammatory antibody targeting complement protein C5a, in patients with acute graft-versus-host disease of the lower GI tract (GI-GVHD). Acute GI-GVHD is a severe and life-threatening rare autoimmune disease that can occur as a complication of stem cell or bone marrow transplantation.3,4,5 The study showed an overall 28-day response rate—defined as improvement from diagnosis in any organ by ≥1 stage, without progression in any other organ and no need for additional therapy—of 77 percent in ALXN1007-treated patients.6

"Alexion has more than 20 years of experience in complement research and discovery, and we are pleased to have late-breaking data from two of our highly innovative, investigational complement inhibitors, ALXN1210 and ALXN1007, presented at EHA (Free EHA Whitepaper)," said Martin Mackay, Ph.D., Executive Vice President and Global Head of R&D at Alexion. "Interim results from the Phase 1/2 study of ALXN1210 in patients with PNH showed rapid, complete, and sustained complement inhibition, as measured by reductions in LDH levels, with a once-monthly dosing regimen in all treated patients. A Phase 2 study is ongoing to evaluate the safety and efficacy of ALXN1210 in additional dosing cohorts evaluating longer dosing intervals."

ALXN1210, a Long-Acting C5 Inhibitor, Results in Rapid and Sustained Reduction of LDH with a Monthly Dosing Interval in Patients with PNH: Preliminary Data from a Dose-Escalation Study (Abstract LB2247) 2

In a poster session, interim results were presented from a Phase 1/2, open-label, 24-week dose-escalating study of ALXN1210 in patients with PNH. The primary efficacy endpoint was the percent change in LDH levels from baseline; other efficacy endpoints included change in blood transfusion requirements and change in hematologic parameters from baseline. Patients with PNH (aged 18 and older; n=13) with mean LDH levels ≥3 times the upper limit of normal and who were complement inhibitor-naïve were separated into two study cohorts. Patients in Cohort 1 (n=6) received either 400 mg or 600 mg induction doses of ALXN1210, followed by a 900 mg maintenance dose once-monthly. Patients in Cohort 2 (n=7) received 600 mg and 900 mg induction doses of ALXN1210, followed by an 1,800 mg maintenance dose once-monthly.

All patients showed rapid reductions in mean LDH levels at Day 8 (the first evaluable time point of the study), which were sustained for up to five once-monthly dosing intervals. At the most recent evaluable time point, the mean percentage reduction in LDH levels from baseline was 85.4 percent in Cohort 1 (Day 148) and 86.0 percent in Cohort 2 (Day 85). Among five patients with one or more transfusions in the year prior to the study, only one patient, from Cohort 1, required a transfusion during treatment with ALXN1210. This patient received two units of packed red blood cells (RBC) while receiving ALXN1210, compared to 12 units of RBC in the six months prior to ALXN1210. In addition, mean levels of hemoglobin, another direct marker of intravascular hemolysis, were improved or stable in both cohorts.

"PNH is a devastating, ultra-rare blood disorder caused by uncontrolled activation of complement, putting patients at risk for severe and life-threatening consequences," said lead author Jong-Wook Lee, M.D., of The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, Korea. "The interim data presented at EHA (Free EHA Whitepaper) suggest that treatment with ALXN1210 results in effective blockade of complement-mediated hemolysis and reduces transfusion requirements in patients with PNH. All patients achieved rapid decreases in LDH levels that were sustained through extended, once-monthly dosing intervals, consistent with the longer half-life of ALXN1210."

No serious adverse events or study withdrawals were observed in either patient cohort. The most common treatment-related adverse events were headache and upper respiratory tract infection (each occurring in 3 patients), which resolved during ongoing treatment with ALXN1210.

Phase 2A Study of ALXN1007, A Novel C5a Inhibitor, in Subjects with Newly Diagnosed Acute Graft-Versus-Host Disease (GVHD) Involving the Lower Gastrointestinal Tract (Abstract LB2269) 6

In a poster session, additional interim results were presented from an ongoing Phase 2, open-label study of ALXN1007 in patients with newly diagnosed acute GI-GVHD. The primary efficacy endpoint is the overall acute GVHD response rate at Day 28. Other efficacy endpoints include complete GI-GVHD response rate at Day 28 and Day 56. Patients were treated once-weekly with 10 mg/kg of ALXN1007 for eight weeks in combination with methylprednisolone or equivalent, with one year of follow-up.

At both Day 28 and Day 56, the overall acute GVHD response rate was 77 percent in 13 evaluable patients. Complete GI-GVHD response rates at Days 28 and 56 were 69 percent and 77 percent, respectively. Additionally, at Day 180, the non-relapse mortality rate from causes other than the underlying malignancy was 12.5 percent, and the overall survival rate was 69.2 percent, among 13 evaluable patients.

The study also evaluated the degree of C5a inhibition relative to PK and acute GI-GVHD response suggesting that higher doses and frequency may be needed to optimize C5a inhibition and maximize clinical response. The trial protocol was subsequently amended to evaluate an ALXN1007 dose of 20 mg/kg weekly and twice-weekly.

Two patients (13 percent) experienced serious treatment-related adverse events and one patient had a grade 2 infusion-related reaction. There were no grade 3 or higher non-serious adverse events related to treatment with ALXN1007. One patient withdrew from the study due to a treatment-emergent adverse event (relapse of T-cell lymphoma). Six deaths were reported, none of which were considered related to treatment with ALXN1007.

About Paroxysmal Nocturnal Hemoglobinuria (PNH)

PNH is an ultra-rare blood disorder in which chronic, uncontrolled activation of complement, a component of the normal immune system, results in hemolysis (destruction of the patient’s red blood cells). PNH strikes people of all ages, with an average age of onset in the early 30s.1 Approximately 10 percent of all patients first develop symptoms at 21 years of age or younger.7 PNH develops without warning and can occur in men and women of all races, backgrounds and ages. PNH often goes unrecognized, with delays in diagnosis ranging from one to more than 10 years.8 In the period of time before Soliris (eculizumab) was available, it had been estimated that approximately one-third of patients with PNH did not survive more than five years from the time of diagnosis.1 PNH has been identified more commonly among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).9,10,11 In patients with thrombosis of unknown origin, PNH may be an underlying cause.1

About ALXN1210

ALXN1210 is a highly innovative, longer-acting C5 antibody being evaluated by Alexion for the treatment of patients with PNH. In early studies, ALXN1210 has demonstrated rapid, complete, and sustained reduction of free C5 activity and a terminal half-life of more than 30 days, which may facilitate a monthly or longer dosing interval.12 Alexion is conducting two clinical studies of ALXN1210 in patients with PNH—a Phase 1/2 dose-escalating study and an open-label, multi-dose Phase 2 study.

About Graft-Versus-Host Disease of the Lower GI tract (GI-GVHD)

GI-GVHD is an immune-mediated disease that affects 10 to 12 percent of patients who receive an allogeneic hematopoietic stem cell transplant.3,4 Patients with severe, acute GI-GVHD have a 30 to 40 percent mortality rate within the first six months post-transplant.13 There are no approved treatments for GI-GVHD.

About ALXN1007

ALXN1007 is a novel anti-inflammatory antibody targeting complement protein C5a being evaluated in a Phase 2 trial for patients with acute GI-GVHD.

About Soliris (eculizumab)

Soliris is a first-in-class terminal complement inhibitor developed from the laboratory through regulatory approval and commercialization by Alexion. Soliris is approved in the U.S. (2007), European Union (2007), Japan (2010) and other countries as the first and only treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. PNH is a debilitating, ultra-rare and life-threatening blood disorder, characterized by complement-mediated hemolysis (destruction of red blood cells). Soliris is also approved in the U.S. (2011), European Union (2011), Japan (2013) and other countries as the first and only treatment for patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, or TMA (blood clots in small vessels). aHUS is a debilitating, ultra-rare and life-threatening genetic disorder characterized by complement-mediated TMA. Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS). For the breakthrough medical innovation in complement inhibition, Alexion and Soliris have received some of the pharmaceutical industry’s highest honors: the Prix Galien USA (2008, Best Biotechnology Product) and France (2009, Rare Disease Treatment).

More information, including the full U.S. prescribing information, on Soliris is available at www.soliris.net.

Important Safety Information

The U.S. product label for Soliris includes a boxed warning: "Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early [see Warnings and Precautions (5.1)]. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies. Immunize patients with a meningococcal vaccine at least two weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. [See Warnings and Precautions (5.1) for additional guidance on the management of the risk of meningococcal infection]. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected. Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program [see Warnings and Precautions (5.2)]. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747)."

In patients with PNH, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, nasopharyngitis (runny nose), back pain and nausea. Soliris treatment of patients with PNH should not alter anticoagulant management because the effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. In patients with aHUS, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, and pyrexia. Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS). Please see full prescribing information for Soliris, including BOXED WARNING regarding risk of serious meningococcal infection.

On June 10, 2016 Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) reported that the United States District Court for the District of Delaware has ruled in favor of Teva in the Company’s patent infringement lawsuit against Hetero USA, Inc., InnoPharma Inc., Hospira Inc., Sagent Pharmaceuticals Inc., and Accord Healthcare Inc., regarding Teva’s TREANDA (bendamustine hydrochloride) for Injection (Filing, 6-K, Teva, JUN 10, 2016, View Source [SID:1234513199]).

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At trial, the defendants alleged that certain claims of U.S. Patents 8,436,190; 8,609,863; 8,791,270; and 8,895,756, listed in the Orange Book for TREANDA, are invalid. The defendants had previously stipulated to infringement of certain claims of these patents. Today the court issued a ruling affirming the validity of the relevant claims of all four patents. As a result, we expect that the court will enter an order enjoining the defendants from launching their respective generic versions of TREANDA until patent expiry in 2026.

"Teva is very pleased that the court has upheld the validity of its patents for the lyophilized formulation of TREANDA," said Rob Koremans, M.D., President and CEO of Teva Global Specialty Medicines. "This ruling is a testament to the strength of Teva’s intellectual property and commitment to defending our bendamustine franchise."

On June 10, 2016 TG Therapeutics, Inc. (NASDAQ:TGTX) reported data presented during the 21st Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) being held in Copenhagen, Denmark (Press release, TG Therapeutics, JUN 10, 2016, View Source [SID:1234513197]). These presentations include long term follow-up data of TGR-1202, the Company’s once daily PI3K delta inhibitor, both alone and in combination with TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody, as well as data presented for the first time from a Phase I/Ib study of TGR-1202 in combination with ibrutinib in patients with relapsed/refractory CLL or MCL.

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Michael S. Weiss, the Company’s Executive Chairman and Interim CEO commented on the data, "EHA is a great opportunity to showcase to the European hematology community the exciting data for TGR-1202 and for the combination of TGR-1202 plus TG-1101 that we recently presented at ASCO (Free ASCO Whitepaper). We were also excited to present for the first time, the safety and preliminary activity of the all oral combination of TGR-1202 and the BTK inhibitor, ibrutinib, by Dr. Matthew Davids and the team from Dana-Farber. We were pleased to report today that the data demonstrates that TGR-1202 at our Phase 3 dose of 800 mg plus full dose ibrutinib appears safe, well-tolerated and produced high response rates, especially in patients with advanced CLL, including one complete response, a depth of response not generally observed with either agent alone. We thank all the investigators involved and look forward to continued enrollment in the combination of TGR-1202 plus ibrutinib, as well as the ongoing triplet combinations with TGR-1202 and TG-1101 in combination with either ibrutinib, bendamustine or pembrolizumab."

The following summarizes the posters presented yesterday and today during the EHA (Free EHA Whitepaper) meeting:

E-Poster Title: Preliminary results of a Phase I/Ib study of ibrutinib in combination with TGR-1202 in patients with relapsed/refractory CLL or MCL

This poster includes data from patients with relapsed or refractory CLL or mantle cell lymphoma (MCL), all of whom were treated with TGR-1202 in combination with ibrutinib. A total of 27 patients were evaluable for safety, 17 patients with CLL and 10 with MCL, and 21 evaluable for efficacy, 11 patients with CLL and 10 with MCL (6 CLL patients were too early for assessment). CLL patients had a median of 2 prior lines of therapy (range 1-6), with 2 patients receiving prior ibrutinib and 2 receiving prior PI3K inhibitors. MCL patients had a median of 3 prior lines of therapy (range 2-5), with 2 patients also receiving prior ibrutinib.

Highlights from this poster include:

82% (9/11) ORR in patients with CLL, with 1 patient achieving a CR confirmed by a negative bone marrow and several other patients approaching a CR radiographically
60% (6/10) ORR in patients with MCL, with clinical benefit observed in two additional patients
The combination was well tolerated with no DLTs observed up to the highest dose tested (800 mg TGR-1202 + full dose ibrutinib) with the toxicity profile being comparable to the additive toxicity of the two agents given individually
In addition to the above E-Poster, the Company is also presenting integrated analysis data from 165 patients with relapsed or refractory hematologic malignancies, which has been previously presented during the ASCO (Free ASCO Whitepaper) conference earlier this week. The data has been separated into two posters evaluating patients with CLL and then patients with NHL.

Long-term follow-up of the next generation PI3K-delta inhibitor TGR-1202 demonstrates safety and high response rates in CLL: Integrated-analysis of TGR-1202 monotherapy and combined with ublituximab (Abstract P207)

Long-term follow-up of the next generation PI3Kδ inhibitor TGR-1202 demonstrates safety and high response rates in NHL: Integrated-analysis of TGR-1202 monotherapy and combined with ublituximab (Abstract P315)

Updated information from the presentations at ASCO (Free ASCO Whitepaper) earlier this week include:

Median Progression Free Survival (PFS) for TGR-1202 monotherapy was 24 months, while median PFS and DOR were not reached for TGR-1202 plus TG-1101 with median follow-up of 10.5 months, supporting our ongoing UNITY-CLL registration Phase 3 trial

Median DOR of 12.1 months observed in DLBCL patients treated with TGR-1202 plus TG-1101, providing a strong rationale for our UNITY-DLBCL registration program

Median DOR not reached in iNHL patients treated with TGR-1202 plus TG-1102 with a median follow-up of 15.8 months, further supporting our UNITY-iNHL registration directed trial, planned to launch by YE 2016
POSTER PRESENTATION DETAILS

A copy of the above mentioned poster presentations are available on the Company’s website at www.tgtherapeutics.com, located on the Publications Page, within the Pipeline section.

On June 10, 2016 Stemline Therapeutics, Inc. (Nasdaq:STML) reported that its SL-401 Phase 2 clinical data in blastic plasmacytoid dendritic cell neoplasm (BPDCN) will be the subject of an oral presentation this weekend at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) being held in Copenhagen, Denmark (Press release, Stemline Therapeutics, JUN 10, 2016, View Source [SID:1234513196]).

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Details on the EHA (Free EHA Whitepaper) presentation are as follows:

Title: Results from ongoing Phase 2 registration study of SL-401 in patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Presenter: Naveen Pemmaraju, M.D., MD Anderson Cancer Center
Abstract No.: S812
Session: Treatment in Specific AML Subgroups
Date/Time: Sunday, June 12, 2016; 9:00 – 9:15 AM CET
Location: Hall C13

Ivan Bergstein, M.D., Stemline’s Chief Executive Officer, commented, "We believe the selection by the EHA (Free EHA Whitepaper) of the SL-401 clinical results in BPDCN for oral presentation, to be delivered this weekend, highlights SL-401’s significant clinical activity in BPDCN, a devastating malignancy of high unmet medical need. Awareness of BPDCN is increasing across both the U.S. and Europe, driven in part by the emergence of this targeted agent, its high level of activity, and a greater understanding of the BPDCN diagnostic criteria."

Dr. Bergstein concluded, "Over the remainder of the year, we plan to continue to enroll first-line and relapsed/refractory patients in this ongoing trial and advance our ongoing interactions with the regulatory authorities. Our goal is to bring this promising agent to market as soon as possible."

On June 10, 2016 Novartis reported Phase III data from RESPONSE-2 showing that Jakavi (ruxolitinib) helped patients with polycythemia vera (PV), who did not have an enlarged spleen and were resistant to or intolerant of hydroxyurea, achieve superior hematocrit control compared to best available therapy (BAT) at 28 weeks (62.2% vs 18.7%, respectively; p<0.0001)[1] (Press release, Novartis, JUN 10, 2016, View Source [SID:1234513182]). The findings were presented for the first time at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Copenhagen, Denmark.

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Polycythemia vera is a rare and incurable blood cancer associated with an overproduction of blood cells that can cause serious cardiovascular complications, such as blood clots, stroke and heart attack[4]. As the disease progresses, the spleen can become enlarged as it works to clear a greater number of blood cells than normal[5]. In this study, patients did not have an enlarged spleen as assessed by physical examination at baseline (spleen palpation) and a majority (approximately 70%) were previously treated with hydroxyurea only, therefore considered less advanced. The remaining patients were treated with multiple lines of therapy (approximately 30%)[1].

"RESPONSE-2 is the first study of this scale to focus on patients with inadequately controlled polycythemia vera in a less advanced phase of the disease," said lead study investigator, Francesco Passamonti, MD, the University of Insubria, Varese, Italy. "The study supports the use of Jakavi as a second-line treatment option to help this patient population gain better control of their disease."

Patients with PV in the study were classified as inadequately controlled based on the modified European LeukemiaNet (ELN) criteria, which defines resistance to or intolerance of hydroxyurea as hematocrit levels greater than 45%, elevated white blood cell count and/or platelet count, and the presence of hydroxyurea-related non-hematologic toxicities[6].

"Given the limited research and treatment options for polycythemia vera, this trial was initiated to gain a better understanding of Jakavi in patients whose disease is not adequately controlled with hydroxyurea," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "The results demonstrate the potential benefit of Jakavi to help manage the disease in patients who have few other options."

In addition to meeting its primary endpoint of proportion of patients achieving hematocrit control, the RESPONSE-2 study showed that nearly five times more patients with PV achieved complete hematologic remission with Jakavi compared to BAT at 28 weeks (23.0% vs 5.3%, respectively; p=0.0019). Patients taking Jakavi also experienced complete resolution of their symptoms related to PV compared to BAT (50.0% vs 7.7%, respectively). Overall, Jakavi was well tolerated. Findings from this study are consistent with data from the RESPONSE pivotal trial evaluating patients with inadequately controlled PV with an enlarged spleen[1,2].

Additionally, Phase III data from the COMFORT-I study were also presented at EHA (Free EHA Whitepaper). These data suggest an overall survival advantage in patients with intermediate-2 or high-risk myelofibrosis (MF) randomized to Jakavi compared to patients randomized to placebo. The five-year survival showed a 31% reduced risk of death (HR=0.69; 95% CI: 0.50, 0.96; p=0.025) in the Jakavi arm despite more than 70% of patients randomized to the placebo arm crossing over to receive treatment with Jakavi (median time to crossover was 41.1 weeks). Patients treated with Jakavi maintained spleen response (>=35% reduction in size) for an average of three years. These findings further support the durable efficacy and long-term safety profile of Jakavi in MF[3].

About the RESPONSE-2 Study
The Phase IIIb RESPONSE-2 (Randomized Study of Efficacy and Safety in POlycythemia Vera with JAK INhibitor Ruxolitinib VerSus BEst Available Care) study evaluated the efficacy and safety of Jakavi versus BAT. The trial randomized 149 patients with PV who were resistant to or intolerant of hydroxyurea, dependent on phlebotomy for hematocrit control and did not have an enlarged spleen. Patients were randomized 1:1, to receive either Jakavi (10 mg twice daily) or BAT, which was defined as investigator-selected monotherapy or observation only[1].

The primary endpoint of the trial was the proportion of patients who achieved hematocrit control at week 28 (without phlebotomy from week 8 to 28 with no more than one phlebotomy eligibility between randomization and week 8). The key secondary endpoint was the proportion of patients who achieved complete hematologic remission (CHR) at week 28. CHR was defined as achieving hematocrit control without the use of phlebotomy, platelet count <=400 x 109/L and white blood cell count <=10 × 109/L, which are all important markers of disease control in PV[1].

In the study, anemia occurred in 16.2% of patients in the Jakavi-treatment arm compared to 2.7% in the BAT arm. The most common non-hematologic adverse events (>=10% of patients) in either the Jakavi or BAT arm were headache (12.2% vs 10.7%, respectively), constipation (10.8% vs 5.3%, respectively), hypertension (10.8% vs 4.0%, respectively), pruritus (10.8% vs 20.0%, respectively), and weight increase (10.8% vs 1.3%, respectively), which were mainly Grade 1 or 2. Patients treated with Jakavi had fewer thromboembolic events compared to patients taking BAT (1 vs 3, respectively)[1].

About the COMFORT-I Study
The Phase III COMFORT-I (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) study included 309 patients with primary MF, post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF) in 89 study locations in Canada, Australia and the United States. Half of the patients (155) received Jakavi (starting dose 15 or 20 mg twice daily) and half (154) received placebo. Patients receiving placebo could crossover to the Jakavi arm after the primary analysis or at any time if they had pre-specified worsening of their enlarged spleen. A final analysis of the study at five years was performed to evaluate the safety and efficacy of Jakavi in patients with MF[3].

Notable adverse events (AE) at the five-year analysis included herpes zoster (10.3% and 13.5% in Jakavi patients and patients who crossed over from placebo, respectively), basal cell carcinoma (7.7% and 9.0%, respectively) and acute myeloid leukemia (5 patients in each arm)[3].

About Polycythemia Vera
Polycythemia vera affects up to three per 100,000 people globally each year[7]. The disease is driven by the dysregulation of the JAK-STAT pathway[8]. It is typically characterized by elevated hematocrit, the volume percentage of red blood cells in whole blood, which can lead to a thickening of the blood and an increased risk of blood clots, as well as an elevated white blood cell and platelet count[4]. This can cause serious cardiovascular complications, such as stroke and heart attack, resulting in increased morbidity and mortality[9]. PV can also persist for many years and in some cases evolve to myelofibrosis (post-PV MF) or acute myeloid leukemia (AML)[10].

A common PV treatment includes phlebotomy, a procedure to remove blood from the body to reduce the concentration of red blood cells, which is used to help maintain a hematocrit level below 45%[4,9]. However, for a subset of patients, phlebotomy may be unsuitable as a permanent treatment option due to its inability to control symptoms or effectively manage the overproduction of red blood cells, therefore cytoreductive agents, such as hydroxyurea, may be added[9]. For patients requiring phlebotomy in combination with hydroxyurea, hematocrit may fluctuate and remain at unsafe levels for significant periods of time[11]. Unfortunately, approximately 25% of patients with PV become resistant to or intolerant of hydroxyurea treatment according to ELN criteria, resulting in inadequate disease control and an increased risk of progression[12].

About Myelofibrosis
Myelofibrosis is a rare and life-threatening blood cancer that affects approximately one in every 100,000 people and has similar survival rates as other malignancies, such as breast cancer and colon cancer[7,13,14,15,16]. In patients with MF, their bone marrow can no longer produce enough normal blood cells, causing the spleen to enlarge[13]. As a result, patients may suffer from debilitating symptoms and have a poor quality of life[17]. Approximately 90% of patients with MF have mutations that directly or indirectly activate the JAK/STAT signaling pathway, which may explain the development of the disease[18].

Although allogeneic stem cell transplantation may cure MF, the procedure is associated with significant morbidity and transplant-related mortality, and is available to less than 5% of patients who are young and fit enough to undergo the procedure[19].

About Jakavi
Jakavi (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. Jakavi is approved by the European Commission for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF. Jakavi is approved in more than 95 countries for patients with MF, including countries in the European Union, Canada, Japan and countries in Asia, Latin and South America, and in 60 countries for patients with PV, including countries in the European Union, Japan and Canada. The exact indication for Jakavi varies by country. Additional worldwide regulatory filings are underway in MF and PV.

Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization outside the United States. Jakavi is marketed in the United States by Incyte Corporation as Jakafi for the treatment of patients with PV who have had an inadequate response to or are intolerant of hydroxyurea and for the treatment of patients with intermediate or high-risk MF.

The recommended starting dose of Jakavi in PV is 10 mg given orally twice daily. The recommended starting dose of Jakavi in MF is 15 mg given orally twice daily for patients with a platelet count between 100,000 cubic millimeters (mm3) and 200,000 mm3, and 20 mg twice daily for patients with a platelet count of >200,000 mm3. Doses may be titrated based on safety and efficacy. There is limited information to recommend a starting dose for MF and PV patients with platelet counts between 50,000/mm3 and <100,000/mm3. The maximum recommended starting dose in these patients is 5 mg twice daily, and patients should be titrated cautiously[20].

Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte Corporation. The safety and efficacy profile of Jakavi has not yet been established outside the approved indications.

Jakavi Important Safety Information for Treatment of Myelofibrosis (MF) and Polycythemia Vera (PV)
Jakavi can cause serious side effects, including a decrease in blood cell count and infections. Complete blood count monitoring is recommended. Dose reduction or interruption may be required in patients with any hepatic impairment or severe renal impairment or in patients developing hematologic adverse reactions such as thrombocytopenia, anemia and neutropenia. Dose reductions are also recommended when Jakavi is co-administered with strong CYP3A4 inhibitors or fluconazole. Use of Jakavi during pregnancy is not recommended, and women should avoid becoming pregnant during Jakavi therapy. Women taking Jakavi should not breast feed. Progressive multifocal leukoencephalopathy (PML) has been reported. Physicians should be alert for neuropsychiatric symptoms suggestive of PML. Hepatitis B viral load (HBV-DNA titer) increases have been reported in patients with chronic HBV infections. Patients with chronic HBV infection should be treated and monitored according to clinical guidelines. Non-melanoma skin cancer (NMSC) has been reported in Jakavi treated patients. Periodic skin examination is recommended. Very common adverse reactions in MF (>10%) include urinary tract infections, anemia, thrombocytopenia, neutropenia, hypercholesterolemia, dizziness, headache, alanine aminotransferase increased, aspartate aminotransferase increased, bruising and weight gain. Common adverse reactions in MF (1 to 10%) include herpes zoster and flatulence. Uncommon adverse reactions in MF include tuberculosis. Very common adverse reactions in PV (>10%) include anemia, thrombocytopenia, hypercholesterolemia, hypertriglyceridemia, dizziness, alanine aminotransferase increased and aspartate aminotransferase increased. Common adverse reactions in PV (1 to 10%) include urinary tract infections, herpes zoster, weight gain, constipation and hypertension.

Please see full Prescribing Information available at www.jakavi.com (link is external).