On May 31, 2015 Gilead Sciences, Inc. (Nasdaq:GILD) reported results from the Phase 3 clinical Study 119 of an investigational use of Zydelig (idelalisib) in combination with ofatumumab in previously-treated patients with chronic lymphocytic leukemia (CLL) (Press release, Gilead Sciences, MAY 31, 2015, View Source;p=irol-newsArticle&ID=2054590 [SID:1234506559]). In Study 119, there was a 73 percent reduction in the risk of disease progression or death in patients receiving Zydelig in combination with ofatumumab compared to ofatumumab alone (hazard ratio (HR) = 0.27; 95 percent CI: 0.19, 0.39; p<0.0001). Detailed results will be presented today during a poster session at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago (Abstract #7023).

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"The data reported today reinforce prior results showing that idelalisib, here in combination with the anti-CD20 monoclonal antibody ofatumumab, not only significantly improved overall and lymph node response rates, but more importantly progression-free survival in patients with previously treated CLL," said Jeffrey A. Jones, MD, MPH, Associate Professor of Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). "Importantly, these improvements were also observed in patients with genetic features typically associated with poor prognosis."

Study 119 was a randomized, controlled, open-label Phase 3 study evaluating the efficacy and safety of Zydelig in combination with ofatumumab. The study enrolled 261 adult patients with previously treated CLL whose disease had progressed less than 24 months following completion of prior therapy, and had not previously been refractory to ofatumumab. Eligible patients were randomized 2:1 to receive an ofatumumab 1,000 mg dosing regimen (12 infusions, first infusion 300mg) over 24 weeks plus Zydelig (150 mg) twice daily (n=174) continuously until disease progression or unacceptable toxicity or an ofatumumab 2,000 mg dosing regimen (12 infusions, first infusion 300mg) over 24 weeks (n=87).

The primary endpoint was progression-free survival (PFS), defined as the time from randomization to definitive disease progression or death assessed by an independent review committee. Median PFS in the Zydelig/ofatumumab arm was 16.3 months, compared to 8.0 months in the ofatumumab monotherapy arm. Statistically significant improvements were also observed for overall response rate (75 percent vs. 18 percent; odds ratio (OR) = 15.9, p<0.0001) and lymph node response rate (93.3 percent vs. 4.9 percent; OR=486.96, p<0.0001). Median PFS in the approximately 40 percent of patients with 17p deletion or TP53 mutation was 13.7 months vs. 5.8 months (HR=0.32, p<0.0001). A statistically significant difference was not achieved in median overall survival (20.9 months vs. 19.4 months; HR=0.74, p=0.27).

The safety profile of Zydelig was similar to prior studies in previously-treated patients with CLL. Grade ≥3 adverse events occurring in the Zydelig plus ofatumumab arm included diarrhea/colitis (20.2 percent), pneumonia (12.7 percent) and febrile neutropenia (11.6 percent).

Based on the Study 119 trial results, Gilead has filed a supplemental New Drug Application (sNDA) with the U.S. Food and Drug Administration to include data from this study in the U.S. label. Gilead plans to submit a supplemental filing to the European Medicines Agency later this year.

"Zydelig has now demonstrated strong efficacy in two randomized Phase 3 studies among previously treated CLL patients," said Norbert Bischofberger, PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer. "We continue to explore the clinical profile of Zydelig in combination with both standard and novel treatment regimens, including seven ongoing or completed Phase 3 clinical trials for B-cell malignancies."

The Zydelig U.S. Prescribing Information includes a BOXED WARNING regarding fatal and serious toxicities of hepatotoxicity, severe diarrhea/colitis, pneumonitis, and intestinal perforation; see below for Important Safety Information.

The use of Zydelig in combination with ofatumumab is investigational and the safety and efficacy of this combination has not yet been established.

Dr. Jones is an uncompensated advisory board member to Gilead and receives research grant support to support this Phase 3 trial at The OSUCCC – James.

About Zydelig (idelalisib)

Zydelig is an oral inhibitor of phosphoinositide 3-kinase (PI3K) delta, a protein that plays a role in the activation, proliferation and viability of B cells, a critical component of the immune system. PI3K delta signaling is active in many B-cell leukemias and lymphomas, and by inhibiting the protein, Zydelig blocks several cellular signaling pathways that drive B-cell viability.

On July 23, 2014, Zydelig received accelerated approval from the U.S. Food and Drug Administration as monotherapy for patients with relapsed follicular lymphoma (FL) or small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies, and full approval in combination with rituximab for patients with relapsed CLL for whom rituximab alone would be considered appropriate therapy due to comorbidities. On September 19, 2014, the European Commission granted marketing authorization for Zydelig as monotherapy in FL patients who are refractory to two prior lines of treatment, and in combination with rituximab for CLL patients who have received at least one prior therapy, or in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemoimmunotherapy.

Additional information about clinical studies of Zydelig and Gilead’s investigational cancer agents can be found at www.clinicaltrials.gov.

Important U.S. Safety Information

BOXED WARNING: FATAL AND SERIOUS TOXICITIES: HEPATIC, SEVERE DIARRHEA, COLITIS, PNEUMONITIS AND INTESTINAL PERFORATION

Fatal and/or serious hepatotoxicity occurred in 14 percent of Zydelig-treated patients. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue Zydelig as recommended.

Fatal and/or serious and severe diarrhea or colitis occurred in 14 percent of Zydelig-treated patients. Monitor for the development of severe diarrhea or colitis. Interrupt and then reduce or discontinue Zydelig as recommended.

Fatal and serious pneumonitis can occur. Monitor for pulmonary symptoms and bilateral interstitial infiltrates. Interrupt or discontinue Zydelig as recommended.

Fatal and serious intestinal perforation can occur in Zydelig-treated patients. Discontinue Zydelig for intestinal perforation.

Contraindications

History of serious allergic reactions, including anaphylaxis and toxic epidermal necrolysis (TEN).
Warnings and Precautions

Hepatotoxicity: Findings were generally observed within the first 12 weeks of treatment and reversed with dose interruption. Upon rechallenge at a lower dose, ALT/AST elevations recurred in 26% of patients. In all patients, monitor ALT/AST every 2 weeks for the first 3 months, every 4 weeks for the next 3 months, and every 1 to 3 months thereafter. If ALT/AST is >3x upper limit of normal (ULN), monitor for liver toxicity weekly. If ALT/AST is >5x ULN, withhold Zydelig and monitor ALT/AST and total bilirubin weekly until resolved. Discontinue Zydelig for recurrent hepatotoxicity. Avoid concurrent use with other hepatotoxic drugs.
Severe diarrhea or colitis: Grade 3+ diarrhea can occur at any time and responds poorly to antimotility agents. Avoid concurrent use with other drugs that cause diarrhea.

Pneumonitis: Evaluate for pneumonitis in patients presenting with pulmonary symptoms such as cough, dyspnea, hypoxia, interstitial infiltrates on radiologic exam, or oxygen saturation decline by ≥5 percent

Intestinal perforation: Advise patients to promptly report any new or worsening abdominal pain, chills, fever, nausea, or vomiting.

Severe cutaneous reactions: One case of TEN occurred in a study of Zydelig in combination with rituximab and bendamustine. Other severe or life-threatening (grade ≥3) cutaneous reactions have been reported. Monitor patients for the development of severe cutaneous reactions and discontinue Zydelig if a reaction occurs.

Anaphylaxis: Serious allergic reactions including anaphylaxis have been reported. Discontinue Zydelig permanently and institute appropriate supportive measures if a reaction occurs.

Neutropenia: Treatment-emergent grade 3-4 neutropenia occurred in 31 percent of Zydelig-treated patients in clinical trials. In all patients, monitor blood counts ≥every 2 weeks for the first 3 months. In patients with neutrophil counts <1.0 Gi/L, monitor weekly.

Embryo-fetal toxicity: Zydelig may cause fetal harm. Women who are or become pregnant while taking Zydelig should be apprised of the potential hazard to the fetus. Advise women to avoid pregnancy while taking Zydelig and to use effective contraception during and at least 1 month after treatment with Zydelig.

Adverse Reactions

Most common adverse reactions (incidence ≥10 percent and ≥2 percent than rituximab alone, all grades) were pyrexia, nausea, pneumonia, diarrhea, chills, rash, vomiting and headache.

Most frequent serious adverse reactions (SAR) were pneumonia (17 percent), pyrexia (9 percent), sepsis (8 percent), febrile neutropenia (5 percent) and diarrhea (5 percent); SAR were reported in 49 percent of patients and 10 percent of patients discontinued due to adverse reactions.

Most common lab abnormalities (incidence ≥30 percent and ≥5 percent than rituximab alone; all grades) were neutrophils decreased, hypertriglyceridemia, hyperglycemia and ALT elevation.

Drug Interactions

CYP3A inducers: Avoid coadministration with strong CYP3A inducers.
CYP3A inhibitors: When coadministered with strong CYP3A inhibitors, monitor closely for Zydelig toxicity.
CYP3A substrates: Avoid coadministration with CYP3A substrates.

Dosage and Administration

Adult starting dose: One 150 mg tablet twice daily, swallowed whole with or without food. Continue treatment until disease progression or unacceptable toxicity. The safe dosing regimen for patients who require treatment longer than several months is unknown.

Dose modification: Consult the Zydelig full Prescribing Information for dose modification and monitoring recommendations for the following specific toxicities: pneumonitis, ALT/AST elevations, bilirubin elevations, diarrhea, neutropenia, and thrombocytopenia. For other severe or life-threatening toxicities, withhold Zydelig until toxicity is resolved and reduce the dose to 100 mg, twice daily, upon resuming treatment. If severe or life-threatening toxicities recur upon rechallenge, Zydelig should be permanently discontinued.

– See more at: View Source;p=irol-newsArticle&ID=2054590#sthash.5MtJF7En.dpuf

On May 30, 2015 CTI BioPharma and Baxter International reported data from PERSIST-1 – a randomized Phase 3 registration-directed trial examining pacritinib for the treatment of myelofibrosis – in a late-breaking oral session at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), May 29-June 2, 2015 in Chicago, Ill (Press release, Baxter International, JUN 5, 2015, View Source [SID:1234505233]). Pacritinib is an investigational oral multikinase inhibitor with specificity for JAK2 and FLT3. Data presented at ASCO (Free ASCO Whitepaper) (Abstract #LBA7006) show that compared to best available therapy (exclusive of a JAK inhibitor), pacritinib therapy resulted in a significantly higher proportion of patients with spleen volume reduction and control of disease-related symptoms. Data were also selected for inclusion in the official ASCO (Free ASCO Whitepaper) Press Program.

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"Myelofibrosis is a difficult-to-treat, rare chronic blood cancer in need of new options that can help overcome the many unique and burdensome symptoms that patients with this disease face on a regular basis, such as blood transfusions and debilitating pain and fatigue," stated Claire Harrison, M.D., Consultant Hematologist, Guy’s and St. Thomas’ NHS Foundation Trust, Guy’s Hospital, London, United Kingdom and one of the principal investigators for PERSIST-1. "Based on data showing improvement in bone marrow function, pacritinib may have the potential to modify disease in the sickest patients as monotherapy and warrants further evaluation in combination with other potential disease-modifying agents."

Myelofibrosis is associated with significantly reduced quality of life and shortened survival. Spleen enlargement (splenomegaly) is a common and debilitating symptom of myelofibrosis. As the disease progresses, the body slows production of important blood cells and within one year of diagnosis the incidence of disease-related thrombocytopenia (very low blood platelet counts), severe anemia, and red blood cell transfusion requirements increase significantly.

PERSIST-1 Findings Presented at ASCO (Free ASCO Whitepaper)
PERSIST-1 is a randomized (2:1), controlled Phase 3 registration-directed trial comparing the efficacy and safety of pacritinib to best available therapy (BAT) – which included a range of currently utilized off-label treatments – in 327 patients with myelofibrosis (primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis), regardless of the patients’ platelet counts. At study entry, 46 percent of patients were thrombocytopenic; 32 percent of patients had platelet counts less than 100,000 per microliter (<100,000/uL); and 16 percent of patients had platelet counts less than 50,000 per microliter (<50,000/uL); normal platelet counts range from 150,000 to 450,000 per microliter. The median duration of treatment was 16.2 months in patients treated with pacritinib, compared to 5.9 months in patients treated with BAT. The majority (79 percent) of patients on the BAT arm eventually crossed over to receive pacritinib therapy.

As previously reported, the trial met its primary endpoint of spleen volume reduction (35 percent or greater from baseline to Week 24 by MRI/CT scan) in the intent-to-treat population (ITT). These results included patients with severe or life-threatening thrombocytopenia. Data presented at ASCO (Free ASCO Whitepaper) show that when measuring the volume of spleen reduction, the greatest difference in treatment arms was observed in evaluable patients with the lowest platelet counts (<50,000/uL platelets) (33.3 percent with pacritinib vs 0 percent with BAT) (p=0.037).

Beyond the statistically significant reductions in spleen volume, patients treated with pacritinib also experienced a sustained improvement in myelofibrosis-associated symptoms or Total Symptom Score (TSS) as measured by the Myeloproliferative Neoplasm Symptom Assessment Form electronic diary (MPN-SAF TSS and MPN-SAF TSS 2.0). The patient-reported outcomes instrument captures in an electronic diary how a patient feels or functions in relation to their health condition or treatment, including: fatigue, concentration, early satiety/fullness, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. When measuring the secondary endpoint (the proportion of patients with a 50 percent or greater reduction in TSS from baseline to Week 24), patients treated with pacritinib experienced greater improvement in their symptoms when compared to BAT, regardless of their baseline platelet counts (ITT patient population: 24.5 percent of pacritinib-treated patients vs 6.5 percent of BAT-treated patients) (p<0.0001); Evaluable patient population: 40.9 percent of pacritinib-treated patients vs 9.9 percent of BAT-treated patients) (p<0.0001).

Twenty-five percent (25%) of patients treated with pacritinib who were severely anemic and transfusion dependent – requiring at least six units of blood in the 90 days prior to study entry – became transfusion independent, compared to zero patients treated with BAT (p<0.05). Among patients with the lowest baseline platelets (<50,000/uL) who received treatment with pacritinib, a significant increase in platelet counts was observed over time compared to BAT (p=0.003) – with a 35 percent increase in platelet counts from baseline to Week 24.

The most common adverse events, occurring in 10 percent or more of patients treated with pacritinib within 24 weeks, of any grade, were: mild to moderate diarrhea (53.2 percent vs 12.3 percent with BAT), nausea (26.8 percent vs 6.6 percent with BAT), anemia (22.3 percent vs 19.8 percent with BAT), thrombocytopenia (16.8 percent vs 13.2 percent with BAT), and vomiting (15.9 percent vs 5.7 percent with BAT). Of the patients treated with pacritinib, 3 discontinued therapy and 13 patients required dose interruption (average one week) for diarrhea. Patients received a daily full dose of pacritinib over the duration of treatment. Gastrointestinal symptoms typically lasted for approximately one week and few patients discontinued treatment due to side effects. There were no Grade 4 gastrointestinal events reported.

"Results from PERSIST-1 add to the growing body of data showing the potential for pacritinib to address an unmet medical need that currently exists for patients with myelofibrosis, particularly patients with severely low platelet counts that result either from their disease or as a side effect from current treatment," said James A. Bianco, M.D., CTI BioPharma’s President and CEO. "Based on the results observed in this trial, we are continuing to advance the broad clinical development program for pacritinib across a range of hematologic malignancies."

"PERSIST-1 is the most inclusive randomized study of patients with myelofibrosis ever conducted, as we believe it is truly representative of healthcare providers’ real-world clinical experience, including patients with advanced disease, severe cytopenias, and a broad range of platelet count levels with the greatest need for effective treatment options," said David Meek, Head of Oncology at Baxter BioScience. "We look forward to advancing the clinical trial program of pacritinib for the treatment of myelofibrosis and to sharing these data with regulatory authorities."

Data will be presented today by Ruben Mesa, M.D., Deputy Director, Mayo Clinic Cancer Center, Chair of the Division of Hematology & Medical Oncology, Mayo Clinic Cancer Center in both the official ASCO (Free ASCO Whitepaper) Press Program (titled ‘Targeted Therapy’) at 8:00 a.m. CT, as well as in a late-breaking oral session at 2:37 p.m. CT.

About the PERSIST Phase 3 Development Program of Pacritinib
Pacritinib is currently being evaluated in two Phase 3 clinical trials, known as the PERSIST program, for patients with myelofibrosis. The PERSIST clinical trials are intended to support a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA). In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high risk myelofibrosis, including but not limited to patients with disease-related thrombocytopenia, patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy, or patients who are intolerant of, or whose symptoms are sub-optimally managed on other JAK2 inhibitor therapy. The FDA’s Fast Track process is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

PERSIST-1 is a randomized (2:1), open-label, multinational Phase 3 clinical trial comparing the efficacy and safety of pacritinib with that of best available therapy (BAT), other than JAK inhibitors, in 327 enrolled patients with primary and secondary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF), without exclusion for low platelet counts. PERSIST-2 is a randomized (2:1), open-label, multinational Phase 3 clinical trial evaluating pacritinib compared to BAT, including the approved JAK1/JAK2 inhibitor dosed according to product label for patients with myelofibrosis whose platelet counts are less than or equal to 100,000 per microliter. The trial is designed to enroll up to 300 patients in North America, Europe, Australia, New Zealand, and Russia. Additional details are available at www.clinicaltrials.gov or www.PERSISTprogram.com.

CTI BioPharma and Baxter BioScience, which is expected to become Baxalta in mid-2015, entered into a worldwide license agreement in November 2013 to develop and commercialize pacritinib. CTI BioPharma and Baxter will jointly commercialize pacritinib in the U.S. while Baxter has exclusive commercialization rights for all indications outside the U.S.

About Pacritinib
Pacritinib is an oral multikinase inhibitor with specificity for JAK2 and FLT3. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia, and lymphoma. The kinase profile of pacritinib suggests its potential therapeutic utility in conditions such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and chronic lymphocytic leukemia (CLL) due to its potent inhibition of c-fms, IRAK1, JAK2, and FLT3.1

About Myelofibrosis and Myeloproliferative Neoplasms
Myelofibrosis is a one of three main types of myeloproliferative neoplasms (MPN), which are a closely related group of hematological blood cancers. The three main types of MPNs are myelofibrosis, polycethemia vera, and essential thrombocythemia.2 Myelofibrosis is a serious and life-threatening chronic bone marrow disorder caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response and scars the bone marrow. The replacement of bone marrow with scar tissue limits its ability to produce red blood cells, prompting the spleen and liver to take over this function. Symptoms that arise from this disease include enlargement of the spleen, anemia, extreme fatigue, and pain.

The estimated prevalence of MPNs suggest there are approximately 300,000 people living with the disease in the U.S. of which myelofibrosis accounts for approximately 18,000 patients.3 In Europe, there is a wide variation of prevalence observed across data sources. Myelofibrosis has a median age of 64 at the time of diagnosis3 and is a progressive disease with approximately 20 percent of patients eventually developing acute myeloid leukemia.4 The median survival for high-risk patients is less than one and a half years; median survival for myelofibrosis patients overall is approximately six years.5

On May 30, 2015 Bellicum Pharmaceuticals reported the presentation of a poster at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) highlighting the potent anti-tumor effects of CAR T cells constructed with its novel, proprietary, dual co-stimulatory domain, "MC" (MyD88/CD40) (Press release, Bellicum Pharmaceuticals, MAY 30, 2015, View Source;p=RssLanding&cat=news&id=2055229 [SID:1234505205]). MC is incorporated alongside Bellicum’s proprietary CaspaCIDe safety switch in the Company’s CIDeCAR product candidates, including BPX-401.

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The studies evaluated in vivo tumor-killing abilities of two different CIDeCARs: CD19-targeted CIDeCAR cells (BPX-401) were evaluated in a Raji lymphoma model, and Her2-targeted CIDeCAR cells were evaluated in an SK-BR-3 breast cancer model.

Study Highlights:

MC co-stimulation resulted in increased T cell proliferation and enhanced efficacy in lymphoma and solid tumor models in vivo compared to control CAR T cells that included the more commonly utilized co-stimulatory molecule, CD28.

The Company’s CD19-targeted CAR (BPX-401) elicited dose-dependent elevation of cytokines, analogous to cytokine release syndrome, but cytokine levels were rapidly normalized upon administration of rimiducid, without loss of tumor control.
The percentage of BPX-401 cells eliminated upon rimiducid administration was dose-dependent across a 2-3 log range.
"We believe the development of more potent CAR T cells will be critical to success in bulky lymphomas and solid tumors," commented Tom Farrell, Bellicum’s President and Chief Executive Officer. "These data suggest that our novel, dual co-stimulatory domain, MC, enhances anti-tumor efficacy compared to traditional CAR constructs.
Furthermore, the risk of toxicity can be mitigated through our proprietary CaspaCIDe safety switch, potentially in such a way that therapeutic benefit can be maintained even when the switch is activated."

The poster, titled "MyD88/CD40-based costimulation to enhance survival and proliferation of chimeric antigen receptor (CAR)-modified T cells," can be accessed on the Events and Presentations page of the Company’s website.

On May 30, 2015 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported results from the Phase III GADOLIN study showing that Gazyva (obinutuzumab) plus bendamustine followed by Gazyva alone provided significant benefit for people with indolent non-Hodgkin’s lymphoma (NHL) that is refractory to Rituxan (rituximab)-based treatment (Press release, Genentech, MAY 30, 2015, View Source [SID:1234506560]). In the study, Gazyva plus bendamustine followed by Gazyva alone reduced the risk of disease worsening or death (progression-free survival, PFS) by 45 percent (HR=0.55, p=0.0001), compared to bendamustine alone. The study was stopped prior to its protocol-specified final analysis due to the high level of benefit seen in the Gazyva arm compared to the bendamustine arm. There were no unexpected safety signals identified with Gazyva.

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"Unfortunately, some people with indolent non-Hodgkin’s lymphoma have disease that is refractory to Rituxan-based therapy, a standard of care treatment. We’re excited by these data showing that Gazyva could help these people who have few treatment options remaining," said Sandra Horning, M.D., chief medical officer and head of Global Product Development.

The late-breaking data from the GADOLIN study will be featured in the official press program of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on Saturday, May 30, at 8:00 A.M. CDT. The data will be presented during ASCO (Free ASCO Whitepaper)’s 51st Annual Meeting by Dr. Laurie Sehn, British Columbia Cancer Agency/University of British Columbia (Abstract #LBA8502, Monday, June 1, 10:09-10:21 A.M. CDT), and subsequently at the 20th annual congress of the European Hematology Association (EHA) (Free EHA Whitepaper) and the 13th International Conference on Malignant Lymphoma (ICML) in June 2015.

Data from this pivotal study will be submitted to the U.S. Food and Drug Administration, European Medicines Agency and other health authorities around the world for approval consideration.

About the GADOLIN Study

GADOLIN (NCT01059630; GA04753g) is a Phase III open-label, multicenter, randomized two-arm study evaluating Gazyva plus bendamustine followed by Gazyva alone for up to two years compared to bendamustine alone. GADOLIN included 413 patients with indolent NHL whose disease progressed during or within six months of prior Rituxan-based therapy. The primary endpoint of the study is progression-free survival (PFS) as assessed by an independent review committee (IRC), with secondary endpoints including PFS as assessed by investigator review, response rate (RR), best response and overall survival (OS).

Results to be presented at ASCO (Free ASCO Whitepaper) showed:

The median PFS was not reached in the Gazyva-based treatment group versus 14.9 months with bendamustine alone (HR=0.55, p=0.0001) as assessed by IRC.

The median PFS with Gazyva-based treatment was more than double that with bendamustine alone (29.2 months vs. 14.0 months, HR=0.52, p<0.0001), as assessed by investigator review.

No unexpected safety signals were identified in the Gazyva-based treatment arm. Grade 3-4 adverse events that occurred in at least two percent of patients in the Gazyva-treated group or bendamustine alone group included low white blood cell count (33 percent vs. 26.3 percent), low blood platelet count (10.8 percent vs. 16.2 percent), infusion-related reactions (10.8 percent vs. 5.6 percent), low red blood cell count (7.7 percent vs. 10.1 percent), low white blood cell count with fever (4.6 percent vs. 3.5 percent), nausea (1 percent vs. 3 percent), fatigue (1.5 percent vs. 2.5 percent), diarrhea (1 percent vs. 2.5 percent), vomiting (2.1 percent vs. 1 percent), respectively.

About Non-Hodgkin’s Lymphoma
There are two main types of lymphoma: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (NHL). NHL represents approximately 85 percent of all lymphomas diagnosed. There are more than 60 different types of NHL that fall under two subsets, aggressive and indolent (slow-growing). According to the American Cancer Society, it is expected that nearly 72,000 people will be diagnosed with NHL in the United States in 2015, and nearly 20,000 will die from the disease.

Most cases of NHL start in B-lymphocytes, cells that are part of the body’s immune system and help to defend the body against infections. B-cell lymphoma develops when these cells become cancerous and begin to multiply and collect in the lymphatic system, such as lymph nodes, lymphatic tissues or the spleen.

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein found only on B-cells. It attacks targeted cells both directly and together with the body’s immune system. Gazyva is thought to have an increased ability to induce direct cell death and induces greater activity in how it recruits the body’s immune system to attack B-cells (antibody dependent cellular cytotoxicity; ADCC) when compared to Rituxan. Gazyva was discovered by Roche Glycart AG, a wholly owned, independent research unit of Roche. In the United States, Gazyva is part of a collaboration between Genentech and Biogen Idec.

Gazyva is being studied in a large clinical program, including the Phase III GOYA and GALLIUM studies. GOYA is comparing Gazyva head-to-head with Rituxan plus chemotherapy in first line diffuse large B-cell lymphoma (DLBCL) and GALLIUM is comparing Gazyva head-to-head with Rituxan plus chemotherapy in first line indolent NHL. Additional combination studies investigating Gazyva with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are planned or underway across a range of blood cancers.

Gazyva Indication

Gazyva is a prescription medicine used with the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.

Important Safety Information

Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that can become serious or life-threatening, including:

Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If a patient has had history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen for hepatitis B before, and monitor the patient for hepatitis during and after, treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes.

Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. A patient’s weakened immune system could put the patient at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems.

Additional possible serious side effects of Gazyva:

Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that may become severe or life threatening, including:

Infusion Reactions: These side effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. If a patient has a reaction, the infusion is either slowed or stopped until the patient’s symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is serious, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take a few steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment.

Signs of infusion reactions may include: dizziness, nausea, chills, fever, vomiting, diarrhea, breathing problems, and chest pain.
Tumor Lysis Syndrome (TLS): Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness.

Infections: While a patient is taking Gazyva, the patient may develop infections. Some of these infections may be severe. Fatal infections have been reported, so the patient should be sure to talk to the doctor if the patient thinks the patient has one. Patients with active infection should not be treated with Gazyva. Infections may continue even after the patient stops taking Gazyva. The patient’s doctor may prescribe medications to help prevent infections. Symptoms of infection include fever and cough.

Low White Blood Cell Count: When a patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, the patient’s doctor will do blood work to check the patient’s white blood cell counts. Neutropenia can develop during or after treatment with Gazyva. It may also last for more than one month. If a patient’s white blood cell count is low, the patient’s doctor may prescribe medication to help prevent infections.

Low Platelet Count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in the blood. This may affect the clotting process. While the patient is taking Gazyva, the patient’s doctor will do blood work to check the patient’s platelet count.
Most common side effects of Gazyva

The most common side effects of Gazyva are infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

Before receiving Gazyva, patients should talk to their doctor about:

Immunizations: Before receiving Gazyva therapy, the patient should tell the patient’s healthcare provider if the patient has recently received or is scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines.

Pregnancy: A patient should tell the doctor if the patient is pregnant, plans to become pregnant, or is breastfeeding. It is not known if Gazyva may harm the patient’s unborn baby or pass into the patient’s breast milk. The patient should use birth control while using Gazyva and for 12 months after treatment. Mothers who have been exposed to Gazyva during pregnancy should discuss the safety and timing of live virus vaccinations for their infants with their child’s healthcare providers. The patient should speak to the doctor about discontinuing Gazyva if the patient is breastfeeding.

Patients must tell their doctor about any side effect that bothers them or that does not go away.

These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the full Prescribing Information, including Boxed WARNINGS, for additional Important Safety Information.

Rituxan Indications

Rituxan (rituximab) is indicated for the treatment of patients with:

Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent

Previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to Rituxan in combination with chemotherapy, as single-agent maintenance therapy

Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy
Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens

Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)
Rituxan is not recommended for use in patients with severe, active infections.

Important Safety Information:

Rituxan can cause serious side effects that can lead to death, including:

Infusion Reactions: may occur during or within 24 hours of the infusion. The patient’s doctor should give the patient medicines before their treatment. Symptoms can include hives, rash, itching, facial or oral swelling, sudden cough, shortness of breath, difficulty breathing, weakness, dizziness, feeling faint, racing heart or chest pain.
Severe Skin and Mouth Reactions: symptoms can include painful sores, ulcers, or blisters on the skin, lips or mouth; peeling skin; rash; or pustules.

Hepatitis B Virus (HBV) Reactivation: may cause serious liver problems including liver failure and death. If patients have had hepatitis B or are carriers of HBV, receiving Rituxan could cause the virus to become an active infection again. Patient should not receive Rituxan if they have active HBV liver disease. The patient’s doctor will do blood tests to check for HBV infection prior to treatment and will monitor the patient during and for several months following their treatment.

Progressive Multifocal Leukoencephalopathy (PML): a rare, serious brain infection that can lead to severe disability and death and for which there is no known prevention, treatment or cure. Symptoms can include difficulty thinking, loss of balance, changes in speech or walking, weakness on one side of the body or blurred or lost vision.

What are the additional possible serious side effects of Rituxan?

Patients must tell their doctor right away about any side effects they experience. Rituxan can cause serious side effects that can lead to death, including:

Tumor Lysis Syndrome (TLS): may cause kidney failure and the need for dialysis treatment, abnormal heart rhythm and can lead to death. The patient’s doctor may give the patient medicines before their treatment to help prevent TLS.

Serious Infections: can happen during and after treatment and can lead to death. These infections may be bacterial, fungal or viral. Symptoms can include fever; cold or flu symptoms; earache or headache; pain during urination; white patches in the mouth or throat; cuts or scrapes that are red, warm, swollen or painful.

Heart Problems: symptoms can include chest pain and irregular heartbeats that may require treatment. The patient’s doctor may need to stop their treatment.

Kidney Problems: the patient’s doctor should do blood tests to check how well the patient’s kidneys are working.
Stomach and Serious Bowel Problems: can include blockage or tears in the bowel that can lead to death. Stomach area pain during treatment can be a symptom.

Low Blood Cell Counts: the patient’s blood cell counts may be monitored during treatment.

The most common side effects of Rituxan are infusion reactions, chills, infections, body aches, tiredness and low white blood cells.

Patients must tell their doctor if they are pregnant, plan to become pregnant or are breastfeeding. It is not known if Rituxan may harm the patient’s unborn baby or pass into the patient’s breast milk. Women should use birth control while using Rituxan and for 12 months after treatment.

Patients must tell their doctor about any side effect that bothers them or that does not go away.

These are not all of the possible side effects of Rituxan. For more information, patients should ask their doctor or pharmacist.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please see the Rituxan full Prescribing Information, including Most Serious Side Effects, for additional important safety information at View Source

Targeting BCR/ABL with tyrosine kinase inhibitors (TKIs) is a proven concept for the treatment of Philadelphia chromosome-positive (Ph+) leukemias. Resistance attributable to either kinase mutations in BCR/ABL or nonmutational mechanisms remains the major clinical challenge. With the exception of ponatinib, all approved TKIs are unable to inhibit the ‘gatekeeper’ mutation T315I. However, a broad spectrum of kinase inhibition increases the off-target effects of TKIs and may be responsible for cardiovascular issues of ponatinib. Thus, there is a need for more selective options for the treatment of resistant Ph+ leukemias. PF-114 is a novel TKI developed with the specifications of (i) targeting T315I and other resistance mutations in BCR/ABL; (ii) achieving a high selectivity to improve safety; and (iii) overcoming nonmutational resistance in Ph+ leukemias. PF-114 inhibited BCR/ABL and clinically important mutants including T315I at nanomolar concentrations. It suppressed primary Ph+ acute lymphatic leukemia-derived long-term cultures that either displayed nonmutational resistance or harbor the T315I. In BCR/ABL- or BCR/ABL-T315I-driven murine leukemia as well as in xenograft models of primary Ph+ leukemia harboring the T315I, PF-114 significantly prolonged survival to a similar extent as ponatinib. Our work supports clinical evaluation of PF-114 for the treatment of resistant Ph+ leukemia.

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