On October 3, 2016 Bristol-Myers Squibb Company (NYSE:BMY) reported new data across eight tumor types evaluating Opdivo (nivolumab) and Yervoy (ipilimumab), as monotherapy or in combination, as well as new assets, to be presented at the 2016 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Copenhagen, Denmark from October 7–11 (Press release, Bristol-Myers Squibb, OCT 3, 2016, View Source [SID:SID1234515557]). Data presented at this congress underscore the Company’s commitment to its portfolio and to discover the next wave of transformational Immuno-Oncology medicines, including combination therapies, for difficult-to-treat cancers.

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"Bristol-Myers Squibb continues to lead the scientific understanding of Immuno-Oncology with an extensive portfolio and a differentiated clinical development program where we have set a high bar of success to look for clear and differentiated improvements over currently available therapies," said Fouad Namouni, M.D., head of development, Oncology, Bristol-Myers Squibb. "We remain focused on expanding the use of the Opdivo and Yervoy combination to more tumors, and bringing forward novel agents and combination regimens in earlier lines of therapy, to help even more patients with cancer."

Bristol-Myers Squibb assets featured in a total of 26 data presentations. A select listing of Presidential Symposia and oral abstract sessions is included below:

CheckMate -064: Baseline tumor T cell receptor sequencing analysis and neo-antigen load is associated with response and survival in melanoma patients receiving sequential Opdivo and Yervoy (Abstract #1047O). Data will be presented during an oral proferred paper session on Friday, October 7 at 4:45 – 5:00 p.m. CEST.
CheckMate -275: First disclosure of efficacy and safety of Opdivo monotherapy in patients with metastatic urothelial cancer who have received prior treatment (Abstract #LBA31_PR). Data will be presented during an oral proffered paper session on Saturday, October 8 at 9:15 – 9:30 a.m. CEST.
CA184-169: First disclosure of overall survival and safety data from a Phase 3 trial evaluating Yervoy at 3 mg/kg vs. 10 mg/kg in patients with metastatic melanoma (Abstract #1106O). Data will be presented during an oral proffered paper session on Saturday, October 8 at 3:37 – 3:50 p.m. CEST.
CA184-029 (EORTC 18071): Initial report of survival data from a Phase 3 trial evaluating Yervoy versus placebo after complete resection of stage III melanoma (Abstract #LBA2_PR). Data will be featured during the ESMO (Free ESMO Whitepaper) Press Program on Saturday, October 8 at 8:15 a.m. CEST and presented during a Presidential Symposium at 5:00 – 5:15 p.m. CEST.
CheckMate -040: Interim analysis of a Phase 1/2 study evaluating the safety and preliminary efficacy of Opdivo in patients with advanced hepatocellular carcinoma (Abstract #615O). Data will be presented during an oral proffered paper session on Sunday, October 9 at 12:00 – 12:15 p.m. CEST.
CheckMate -141: Evaluation of patient-reported outcomes data in recurrent or metastatic squamous cell carcinoma of the head and neck treated with Opdivo or investigator’s choice (Abstract #LBA4_PR). Data will be presented during a Presidential Symposium on Sunday, October 9 at 4:25 – 4:40 p.m. CEST.
CheckMate -026: Phase 3 trial of Opdivo versus investigator’s choice of platinum-based doublet chemotherapy as first-line therapy for stage IV/recurrent PD-L1 positive non-small cell lung cancer (Abstract #LBA7_PR). Data will be presented during a Presidential Symposium on Sunday, October 9 at 5:35 – 5:50 p.m. CEST.
The full set of data to be presented by Bristol-Myers Squibb include:

Bladder

CheckMate -275: Efficacy and safety of nivolumab monotherapy in patients with metastatic urothelial cancer who have received prior treatment; results from the phase 2 study

Author: Galsky
Abstract # LBA31_PR
Proffered Paper Session, Genitourinary Tumors, Non-Prostate
Saturday, October 8, 2016, 9:15 – 9:30 a.m. CEST, Madrid

CheckMate -032: Nivolumab monotherapy in metastatic urothelial cancer: Updated efficacy by subgroups and safety results

Author: J. Rosenberg
Abstract #784P
Poster Session, Genitourinary Tumours, Non-Prostate
Sunday, October 9, 2016, 1:00 – 2:00 p.m. CEST, Hall E

Colorectal

CheckMate -142: Nivolumab ± ipilimumab treatment efficacy, safety, and biomarkers in patients with metastatic colorectal cancer with and without high microsatellite instability

Author: M. Overman
Abstract #479P
Poster Session, Gastrointestinal Tumours, Colorectal
Saturday, October 8, 2016, 1:00 – 2:00 p.m. CEST, Hall E

Glioblastoma

CheckMate -548: A randomized phase 2, single-blind study of temozolomide and radiotherapy combined with nivolumab or placebo in newly diagnosed adult patients with tumor O6-methylguanine DNA methyltransferase-methylated glioblastoma

Author: M. Weller
Abstract # 356TiP
Poster Session, CNS Tumors
Sunday, October 9, 2016, 1:00 – 2:00 p.m. CEST, Hall E

Head and Neck

Safety of the natural killer cell-targeted anti-KIR antibody, lirilumab, in combination with nivolumab or ipilimumab in two phase 1 studies in advanced refractory solid tumors

Author: N. Segal
Abstract #1086P
Poster Session, Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)
Sunday, October 9, 2016, 1:00 – 2:00 p.m. CEST, Hall E

CheckMate -651: A randomized, open-label, phase 3 study of nivolumab in combination with ipilimumab vs extreme regimen (cetuximab + cisplatin/carboplatin + fluorouracil) as first-line therapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck

Author: A. Argiris
Abstract #1016TiP
Poster Session, Head and Neck Cancer
Sunday, October 9, 2016, 1:00 – 2:00 p.m. CEST, Hall E

CheckMate -714: Double-blind, two-arm, phase 2 study of nivolumab in combination with ipilimumab versus nivo and ipi-placebo as first-line therapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck

Author: R. Haddad
Abstract #1017TiP
Poster Session, Head and Neck Cancer
Sunday, October 9, 2016, 1:00 – 2:00 p.m. CEST, Hall E

CheckMate -141: Evaluation of patient-reported outcomes data in recurrent or metastatic squamous cell carcinoma of the head and neck treated with nivolumab or investigator’s choice

Author: K. Harrington
Abstract # LBA4_PR
Presidential Symposium 2
Sunday, October 9, 2016, 4:25 – 4:40 p.m. CEST, Copenhagen

Hepatocellular Carcinoma

CheckMate -040: Safety and preliminary efficacy of nivolumab in patients with advanced hepatocellular carcinoma: Phase 1/2 interim analysis

Author: I. Melero
Abstract # 615O
Proffered Paper, Gastrointestinal Tumors, Non-Colorectal 2
Sunday, October 9, 2016, 12:00 – 12:15 p.m. CEST, Vienna

Lung

CheckMate -017 and -057: Healthcare resource utilization in patients with advanced non-small cell lung cancer based on treatment-related adverse events

Author: M. Venkatachalam
Abstract #1220P
Poster Session, NSCLC, Metastatic
Saturday, October 8, 2016, 1:00 – 2:00 p.m. CEST, Hall E

Cost of care in first line advanced non-small cell lung cancer patients: Chemotherapy vs. targeted therapy

Author: J. Radtchenko
Abstract #1273P
Poster Session, NSCLC, Metastatic
Saturday, October 8, 2016, 1:00 – 2:00 p.m. CEST, Hall E

FRACTION-Lung: A phase 2, fast real-time assessment of combination therapies in immuno-oncology trial in patients with advanced non-small cell lung cancer

Author: P. Fracasso
Abstract #1295TiP
Poster Session, NSCLC, Metastatic
Saturday, October 8, 2016, 1:00 – 2:00 p.m. CEST, Hall E

The humanistic burden of small cell lung cancer: A systematic review of health-related quality of life literature

Author: C. Panter
Abstract: #1429P
Poster Session, SCLC
Saturday, October 8, 2016, 1:00 – 2:00 p.m. CEST, Hall E

CheckMate -017 and CheckMate -057: Long-term outcomes with nivolumab versus docetaxel in patients with advanced non-small cell lung cancer: two-year update

Author: F. Barlesi
Abstract #1215PD
Poster Discussion, NSCLC, Metastatic
Sunday, October 9, 2016, 2:45 – 4:15 p.m. CEST (3:46 – 4:06 p.m. CEST), Oslo

CheckMate -057: Overall health status in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel

Author: M. Reck
Abstract #1217PD
Poster Discussion, NSCLC, Metastatic
Sunday, October 9, 2016, 2:45 – 4:15 p.m. CEST (3:46 – 4:06 p.m. CEST), Oslo

A phase 1/2 trial of a monoclonal antibody targeting fucosyl GM1 in relapsed/refractory small cell lung cancer: Safety and preliminary efficacy

Author: Q. Chu
Abstract #1427PD
Poster Discussion, Non-Metastatic NSCLC and Other Thoracic Malignancies
Monday, October 10, 2016, 3:00 – 4:00 p.m. CEST (3:20 – 3:30 p.m. CEST), Berlin

CheckMate -026: A phase 3 trial of nivolumab vs investigator’s Choice of platinum-based doublet chemotherapy as first-line therapy for stage IV/recurrent programmed death ligand 1−positive non-small cell lung cancer

Author: M. Socinski
Abstract #LBA7_PR
Presidential Symposium 2
Sunday, October 9, 2016, 5:35 – 5:50 p.m. CEST, Copenhagen

Melanoma

Baseline tumor T cell receptor sequencing analysis and neo antigen load is associated with benefit in melanoma patients receiving sequential nivolumab and ipilimumab

Author: J. Weber
Abstract #1047O
Proffered Paper, Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)
Friday, October 07, 2016, 4:45 – 5:00 p.m. CEST, Copenhagen

Overall survival and safety results from a phase 3 trial of ipilimumab at 3 mg/kg vs. 10 mg/kg in patients with metastatic melanoma

Author: P. Ascierto
Abstract #1106O
Proffered Paper, Melanoma and Other Skin Tumors
Saturday, October 8, 2016, 3:37 – 3:50 p.m. CEST, Copenhagen

Ipilimumab vs. placebo after complete resection of stage III melanoma: final overall survival results from the EORTC 18071 randomized, double-blind, phase 3 trial

Author: L. Eggermont
Abstract #LBA2_PR
Presidential Symposium 1
Saturday, October 8, 2016, 5:00 – 5:15 p.m. CEST, Copenhagen

Safety profile of nivolumab and ipilimumab combination therapy in patients with advanced melanoma

Author: M. Sznol
Abstract #1123P
Poster Session, Melanoma And Other Skin Tumors
Sunday, October 9, 2016, 1:00 – 2:00 p.m. CEST, Hall E

Safety of reduced infusion times for nivolumab plus ipilimumab and nivolumab alone in advanced melanoma

Author: S. Martin-Algarra
Abstract #1125P
Poster Session, Melanoma and Other Skin Tumors
Sunday, October 9, 2016, 1:00 – 2:00 p.m. CEST, Hall E

PD-L1 expression as a biomarker for nivolumab plus ipilimumab and nivolumab alone in advanced melanoma: A pooled analysis

Author: G. Long
Abstract #1112PD
Poster Discussion, Melanoma and Other Skin Tumors
Monday, October 10, 2016, 11:00 a.m. – 12:00 p.m. CEST (11:30 – 11:50 a.m. CEST), Rome

Renal Cell Carcinoma

Cost-effectiveness of nivolumab in patients with advanced renal cell carcinoma in Sweden

Author: S. Johal
Abstract #1032P
Poster Session, Health Economics
Sunday, October 9, 2016, 1:00 – 2:00 p.m. CEST, Hall E

CheckMate -016: Updated results from a phase 1 study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma

Author: H. Hammers
Abstract #1062P
Poster Session, Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)
Sunday, October 9, 2016, 1:00 – 2:00 p.m. CEST, Hall E

Pan-Tumor

Assessment of nivolumab benefit-risk profile from a 240-mg flat dose versus a 3-mg/kg dosing regimen in patients with solid tumors

Author: X. Zhao
Abstract #1098P
Poster Session, Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)
Sunday, October 9, 2016, 1:00 – 2:00 p.m. CEST, Hall E

On October 3, 2016 Exosome Diagnostics, Inc. reported that it has entered into an agreement with Amgen to evaluate the potential to advance drug development with Exosome’s proprietary liquid biopsy diagnostics technology and platform (Press release, Exosome Diagnostics, OCT 3, 2016, View Source [SID:SID1234515554]). Under the terms of the agreement, the companies will collaborate to identify a potential liquid biopsy diagnostic. Financial terms of the agreement were not disclosed.

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Liquid biopsies are effective in advancing therapeutics because of their distinct advantage over tissue biopsies. A significant advantage is that they are less invasive, resulting in fewer complications and risks to the patient during sample collection. Liquid biopsies enable easier sample collection and may help facilitate patient enrollment into trials.

"We are excited to initiate this agreement with Amgen on developing technology that may advance the use of liquid biopsy tests in clinical development," stated Mario Morken, Head of Business Development for Exosome Diagnostics. "Exosome Diagnostic’s technology and expertise allows for the development of highly sensitive liquid biopsy assays."

"The strategy and positioning of the company since the beginning of 2016 is garnering significant results, and we look forward to expounding upon these successes," stated John Boyce, President and CEO of Exosome Diagnostics.

On September 27, 2016, Infinity Pharmaceuticals, Inc. (the "Company" or "we") reported that it entered into a second amendment (the "Second Amendment") to our agreement with Intellikine LLC ("Intellikine" and such agreement, as amended, the "Intellikine Agreement") (Filing, 8-K, Infinity Pharmaceuticals, OCT 3, 2016, View Source [SID:SID1234515550]).

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Under the Second Amendment, effective upon the execution of a transaction in which we or our affiliates (i) grant a license or sublicense of rights under certain intellectual property to use, develop and/or commercialize our product candidate IPI-145 or (ii) sell, in an asset sale, any rights necessary to practice IPI-145 (such transaction, a "Qualifying Transaction"), all milestones for our first licensed compound or product under the Intellikine Agreement shall be deemed satisfied as if they had been achieved by IPI-145, and all of our obligations to report the achievement of such milestones and to make accompanying milestone payments to Intellikine for our first licensed compound or product shall be terminated. Additionally, upon the execution of a Qualifying Transaction, our obligation to use diligent efforts to develop products under the Intellikine Agreement shall be reduced from two products to one. We will pay Intellikine fifty percent (50%) of all revenue arising from each Qualifying Transaction, subject to certain exceptions.
The foregoing description of the Second Amendment does not purport to be complete and is qualified in its entirety by reference to the complete text of the Second Amendment, which we intend to file with the Securities and Exchange Commission as an exhibit to our Quarterly Report on Form 10-Q for the period ending September 30, 2016.

On October 3, 2016 Amgen (NASDAQ:AMGN) reported that the Journal of Clinical Oncology (JCO) published results from the Phase 1/2 ‘205 single-arm trial evaluating BLINCYTO (blinatumomab) in pediatric patients with Philadelphia chromosome‑negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) (Press release, Amgen, OCT 3, 2016, View Source [SID:SID1234515549]). Based on data from an exploratory pooled analysis of 70 patients who received the recommended dose of BLINCYTO in the Phase 1 or Phase 2 portions of the study, 27 patients (39 percent, 95 percent confidence interval [CI], 27–51 percent) achieved complete remission within the first two cycles.

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The most frequent grade ≥3 adverse events (AEs) among the patients who received the recommended dose were anemia (36 percent), thrombocytopenia (21 percent), febrile neutropenia (17 percent), hypokalemia (17 percent) and neutropenia (17 percent). The most common AEs overall were pyrexia (80 percent), anemia (41 percent), nausea (33 percent) and headache (30 percent).

"This study showed that BLINCYTO can induce deep molecular remissions in children with highly refractory, multiply relapsed ALL," said senior author Lia Gore, M.D., professor of Pediatrics, Medical Oncology and Hematology, University of Colorado Anschutz Medical Campus.

"Pediatric patients with relapsed or refractory Ph- B-cell precursor ALL are in critical need of new treatment options," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The publication of this data in the Journal of Clinical Oncology provides clinical evidence of the potential of BLINCYTO in this patient population and underscores the significance of the recent regulatory approval for use of BLINCYTO in these patients."

Among patients who achieved complete remission within the first two cycles of treatment, 52 percent had a complete minimal residual disease (MRD) response, a measure of eradication of residual disease at the molecular level. Complete MRD response was an exploratory endpoint in both phases of the study.

Data from the ‘205 study were the basis of a supplemental Biologics License Application (sBLA) for BLINCYTO to include new data supporting the treatment of pediatric patients with Ph- relapsed or refractory B-cell precursor ALL. On Aug. 30, 2016, the U.S. Food and Drug Administration (FDA) approved the sBLA for BLINCYTO to include this new data supporting the treatment of pediatric patients with Ph- relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval, and continued approval may be contingent upon verification of clinical benefit in subsequent trials.

ALL is a rapidly progressing cancer of the blood and bone marrow. Although very rare in adults, it is the most common type of cancer in children.1,2 Of the children diagnosed with ALL in the U.S. each year, approximately 15-20 percent (375-500) will experience relapse.3-5 Prognosis for children with ALL who are refractory or experience a relapse is extremely poor, and post-relapse survival is only achieved in 40-50 percent of patients.6-8

About Study ‘205
Study ‘205 evaluated the safety and efficacy of BLINCYTO in a Phase 1/2 open-label, multicenter, single-arm study in 93 pediatric patients with Ph- relapsed or refractory B-cell precursor ALL (second or later bone marrow relapse, any marrow relapse after allogeneic hematopoietic stem cell transplantation [alloHSCT], or refractory to other treatments and had >25 percent blasts in bone marrow). Treatment in this study has been completed and subjects are being monitored for long-term efficacy.

BLINCYTO was administered as a continuous intravenous infusion. The recommended dose for this study was determined to be 5 μg/m2/day on Days 1-7 and 15 μg/m2/day on Days 8-28 for cycle 1, and 15 μg/m2/day on Days 1-28 for subsequent cycles. Dose adjustment was possible in case of adverse events. Patients who responded to BLINCYTO, but later relapsed, had the option to be retreated with BLINCYTO.

The treated population included 70 patients who received at least one infusion of BLINCYTO at the recommended dose; the median number of treatment cycles was one (range: 1 to 5). Among treated patients, the median age was eight years (range: seven months to 17 years), 40 out of 70 (57.1 percent) had undergone alloHSCT prior to receiving BLINCYTO, and 39 out of 70 (55.7 percent) had refractory disease. Four patients had less than the 25 percent bone marrow blasts required for protocol entry, but had more than five percent.

About BLINCYTO (blinatumomab)
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

BLINCYTO was granted breakthrough therapy, priority review and orphan drug designations by FDA, and is now approved in the U.S. for the treatment of Ph- relapsed or refractory B-cell precursor ALL.

In November 2015, BLINCYTO was granted conditional marketing authorization in the European Union for the treatment of adults with Ph- relapsed or refractory B-cell precursor ALL.

BLINCYTO U.S. Product Safety Information

Important Safety Information Regarding BLINCYTO (blinatumomab) U.S. Indication
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications
BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO as outlined in the Prescribing Information (PI).
Neurological Toxicities: Approximately 64% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. The median time to onset of any neurological toxicity was 4 days. The most common (≥ 10%) manifestations of neurological toxicity were headache, tremor, dizziness, and altered state of consciousness. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 17% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The neurological toxicity profile varied by age group. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO as outlined in the PI.

Infections: Approximately 25% of patients receiving BLINCYTO experienced serious infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.

Tumor Lysis Syndrome (TLS): TLS, which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.

Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.

Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.

Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment. The median time to onset of elevated liver enzymes was 3 days. In patients receiving BLINCYTO, the majority of these events were observed in the setting of CRS. The median time to onset for these events was 15 days. Grade 3 or greater elevations in liver enzymes occurred in 6% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.

Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO and dexamethasone as needed.

Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO treatment, during treatment, and until immune recovery following last cycle of BLINCYTO.
Adverse Reactions

The most common adverse reactions (≥ 20%) in the safety population studied in clinical trials were pyrexia (66%), headache (34%), nausea (27%), edema (26%), hypokalemia (26%), anemia (25%), febrile neutropenia (24%), neutropenia (22%), thrombocytopenia (20%), and abdominal pain (20%). The safety population included 225 patients weighing 45 kg or more and 57 patients weighing less than 45 kg. For some adverse reactions, there were differences in the incidence rates by age subgroup.
In patients weighing greater than or equal to 45 kg, serious adverse reactions were reported in 61% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia (9%), pyrexia (6%), sepsis (5%), pneumonia (5%), device-related infection (4%), neutropenia (3%), tremor (3%), overdose (3%), encephalopathy (3%), infection (2%), confusion (3%) and headache (2%).
In patients weighing less than 45 kg, serious adverse reactions were reported in 51% of patients. The most common serious adverse reactions (≥ 2%) included pyrexia (12%), febrile neutropenia (9%), cytokine release syndrome (4%), convulsion (4%), device-related infection (4%), hypoxia (4%), sepsis (4%), and overdose (4%).
U.S. Dosage and Administration Guidelines

BLINCYTO is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide, for BLINCYTO at www.BLINCYTO.com.

On October 3, 2016 Jazz Pharmaceuticals plc (Nasdaq; JAZZ) reported the initiation of a rolling submission of a New Drug Application (NDA) to the United States (U.S.) Food and Drug Administration (FDA) on September 30, 2016, seeking marketing approval of Vyxeos (cytarabine and daunorubicin liposome injection), an investigational agent for the treatment of acute myeloid leukemia (AML) (Press release, Jazz Pharmaceuticals, OCT 3, 2016, View Source [SID:SID1234515536]). The company expects to complete the submission of the NDA by early 2017, and will request a priority review.

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"Our initiation of the rolling NDA submission for Vyxeos brings us closer to an important goal of providing a new treatment option for patients with acute myeloid leukemia, a devastating and life-threatening disease," said Karen Smith M.D., Ph.D., global head of research and development and chief medical officer at Jazz Pharmaceuticals. "AML represents a disease area within the hematological cancers, where there remains a significant unmet medical need. Vyxeos, if approved, would be the first new treatment demonstrating a significant advancement in treating AML in over 20 years."

Vyxeos was granted Breakthrough Therapy Designation in May 2016 for the treatment of adults with therapy-related AML or AML with myelodysplasia-related changes. The FDA grants Breakthrough Therapy designation to expedite the development and review of new medicines that are intended to treat serious or life-threatening diseases when the clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on at least one clinically significant endpoint. The Breakthrough Therapy designation allows a company to submit individual sections of its NDA for review by the FDA as they are completed rather than waiting until the entire application is complete before it can be submitted and reviewed.

Celator Pharmaceuticals, Inc. completed and announced the results of its Phase 3 trial evaluating Vyxeos in patients with high-risk AML in March 2016. Jazz Pharmaceuticals completed the acquisition of Celator Pharmaceuticals in July 2016.

About Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a rapidly progressing and life-threatening blood cancer that rises in frequency with age.1 The American Cancer Society estimates that there will be 19,950 new cases of AML and 10,430 deaths from AML in the U.S. in 2016.2 In the European Union, the number of new cases is estimated to be 20,100 in 2016.3

The median age at diagnosis is 67 and with rising age there is progressive worsening of prognosis.1,4 Advancing age is associated with increasing risk of specific chromosomal/mutational changes and risk of pre-malignant marrow disorders which give rise to more aggressive and less responsive forms of AML.5,6 As patients age there is also reduced tolerance for intensive chemotherapy.7 As a consequence, advances in supportive care, intensive chemotherapy, and bone marrow transplantation have primarily benefitted younger patients with approximately one third of patients 18-60 years of age achieving cure.5,7 Older patients have not achieved higher rates of cure or improved upon a 5-year survival rate of 10-20% in spite of 40 years of research. 7, 8

About Vyxeos

Vyxeos (cytarabine and daunorubicin liposome injection), or CPX-351, is a combination of cytarabine and daunorubicin encapsulated within a nano-scale liposome at a 5:1 molar ratio. Vyxeos was granted orphan drug status by the FDA and the European Commission for the treatment of acute myeloid leukemia. Vyxeos was granted Breakthrough Therapy Designation for the treatment of adults with therapy-related AML or AML with myelodysplasia-related changes and was also granted Fast Track designation by the FDA for the treatment of older patients with secondary AML.