On February 14, 2017 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX), an oncology company developing innovative medicines and other products for targeting and treating cancer, reported that enrollment of an investigator initiated Phase 1 clinical trial with 131-I-MIP-1095 (1095) has begun at MSK (Press release, Progenics Pharmaceuticals, FEB 14, 2017, View Source [SID1234517717]). 1095 is one of Progenics’ PSMA-targeted small molecule radiopharmaceutical candidates being developed for the treatment of metastatic prostate cancer.

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1095 is designed to bind to the extracellular domain of prostate specific membrane antigen (PSMA), a protein that is expressed in greater than 95% of prostate cancer cells, and upon binding, internalized by the prostate cancer cells where its iodine-131 beta particles kill the tumor cells. When administered under a compassionate use setting, 1095 was well tolerated and demonstrated markedly reduced PSA levels and bone pain in a group of heavily-pretreated advanced prostate cancer patients (N=28) following a single cycle of treatment.1

"MIP 1095 holds the promise of optimizing tumor-specific delivery of radiation, with the added potential benefit of rapid clearance of the molecule and its radioactive payload that can minimize radiation exposure to normal tissues," said Michael J. Morris, MD of Memorial Sloan Kettering Cancer Center, and lead investigator of the study. "The totality of the preclinical and compassionate use data provides strong support for 1095 in metastatic castration-resistant prostate cancer, and I look forward to further evaluating this drug in the clinical setting."

This Phase 1 open-label dose-escalation study will enroll approximately 40 patients with mCRPC who have demonstrated tumor avidity to 1095. The primary objectives of this study include determination of maximum tolerated dose, safety and tolerability, biodistribution, and efficacy. Findings from this trial will guide the decision of an optimal dose for a Phase 2 trial.

"The initiation of this trial reflects our commitment to advancing PSMA-targeted candidates that have the potential to transform how prostate cancer is detected, managed and treated," said Mark Baker, CEO of Progenics. "The insights we gain from this trial will help guide the design of the future clinical development program of 1095."

About 1095

Progenics’ small molecule therapeutic candidate 1095 is designed to bind to the extracellular domain of prostate specific membrane antigen (PSMA), a protein that is expressed in >95% of prostate cancer cells, and upon binding, to be internalized by the prostate cancer cells, where its iodine-131 beta particles kill the malignant cell. The ability to specifically deliver radiation to prostate cancer cells anywhere in the body allows a commonly used therapy (radiation) to be used with precision to attack systemic disease. Preclinical data has shown high tumor uptake and a favorable tumor to kidney discrimination yielding a lethal radiation dose to the tumor while minimizing normal tissue dose. In human prostate cancer mouse models, the compound, administered in single or multiple dose schedules, significantly reduced tumor burden for a prolonged period of time and enhanced survival with no significant signs of toxicity. When used in a compassionate use setting, 1095 markedly reduced PSA levels and bone pain in a group of 22 heavily-pretreated advanced prostate cancer patients.

On February 14, 2017 Incyte Corporation (Nasdaq:INCY) reported 2016 fourth-quarter and year-end financial results, highlighting strong revenue growth driven by increased sales of Jakafi (ruxolitinib) in the U.S. and Iclusig (ponatinib) in Europe, and royalties from ex-U.S. sales of Jakavi (ruxolitinib) by Novartis (Press release, Incyte, FEB 14, 2017, View Source [SID1234517714]).

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Additionally, Incyte is providing financial guidance for 2017.

“We have had a very productive year at Incyte, during which we expanded our geographic footprint to include Europe and further advanced our clinical portfolio, including the recently announced expansion of the epacadostat development program,” stated Hervé Hoppenot, Incyte’s Chief Executive Officer. “Having now surpassed $1 billion in total annual revenue for the first time, we believe we are in a strong position to execute on our discovery and development objectives and build a global biopharmaceutical company bringing medicines to patients in need.”
Baricitinib, a potential new oral treatment for patients with rheumatoid arthritis (RA) licensed to Eli Lilly and Company (Lilly), is now approved in Europe as Olumiant and is under regulatory review globally. The European approval of Olumiant triggers a $65 million payment to Incyte from Lilly, and Incyte is eligible to receive additional potential milestone payments, as well as royalties on sales of Olumiant. Incyte has recently opted into co-development of multiple new indications for baricitinib, including psoriatic arthritis, in which Lilly is expected to begin a Phase 3 trial in 2017.

Incyte continues to expand its development portfolio—the Company anticipates the initiation of new pivotal trials in at least six indications from its broad late-stage portfolio during 2017 and is conducting four Phase 2 trials which, if successful, could also potentially act as registration-enabling studies. Two recent strategic collaborations have added to Incyte’s early-stage R&D programs—the alliance with Merus provides access to bispecific drug discovery and the licensing agreement with Calithera adds INCB01158, a first-in-class oral arginase inhibitor, to Incyte’s immuno-oncology development portfolio.

Portfolio Update
Cancer – Targeted Therapies
The pivotal program investigating ruxolitinib as a treatment for patients with graft-versus-host disease (GVHD) has begun. REACH1, the pivotal Phase 2 trial in patients with steroid-refractory acute GVHD, enrolled its first patient in December 2016; the REACH2 and REACH3 randomized Phase 3 trials in steroid-refractory acute and steroid-refractory chronic GVHD, respectively, are expected to begin in 2017 in collaboration with Novartis.
A pivotal program of ruxolitinib as a treatment for patients with essential thrombocythemia is also expected to begin in 2017.
Itacitinib (formerly INCB39110), Incyte’s selective JAK1 inhibitor, is anticipated to enter a global pivotal development program for the treatment of patients with treatment-naïve acute GVHD during 2017.
In January 2017, Incyte disclosed its FGFR4 inhibitor discovery program, the lead molecule from which, INCB62079, is expected to enter proof-of-concept clinical trials during 2017.

Indication Status Update
Ruxolitinib (JAK1/JAK2) Steroid-refractory acute GVHD Pivotal (REACH1) trial underway; Phase 3 (REACH2) trial expected to begin in 2017
Ruxolitinib (JAK1/JAK2) Steroid-refractory chronic GVHD Phase 3 (REACH3) trial expected to begin in 2017
Ruxolitinib (JAK1/JAK2) Essential thrombocythemia Pivotal program expected to begin in 2017
Itacitinib (JAK1) Treatment-naïve acute GVHD Pivotal program expected to begin in 2017
Itacitinib (JAK1) Non-small cell lung cancer Phase 1/2 in combination with osimertinib (EGFR)
INCB52793 (JAK1) Advanced malignancies Phase 1/2 dose-escalation
INCB50465 (PI3Kδ) Diffuse large B cell lymphoma Phase 2 (CITADEL-202) expected to begin in first half of 2017
INCB54828 (FGFR1/2/3) Bladder cancer, cholangiocarcinoma; 8p11 MPNs Phase 2
INCB54329 (BRD) Advanced malignancies Phase 1/2 dose-escalation
INCB57643 (BRD) Advanced malignancies Phase 1/2 dose-escalation
INCB53914 (PIM) Advanced malignancies Phase 1/2 dose-escalation
INCB59872 (LSD1) Acute myeloid leukemia, small cell lung cancer Phase 1/2 dose-escalation
INCB62079 (FGFR4) Hepatocellular carcinoma Phase 1/2 dose-escalation expected to begin in 2017

Cancer – Immune Therapies
In January 2017, Incyte and Merck announced the decision to expand the clinical development program investigating epacadostat with pembrolizumab, and plan to initiate Phase 3 trials of the combination in four additional tumors beyond melanoma: non-small cell lung cancer, renal cell carcinoma, bladder cancer and squamous cell carcinoma of the head and neck. These Phase 3 trials are expected to begin in 2017.
In January 2017, Incyte announced that it licensed worldwide rights from Calithera Biosciences to develop and commercialize INCB01158, a first-in-class, oral arginase inhibitor in hematology and oncology indications.
In February 2017, Incyte and Agenus announced an amended agreement, converting the ongoing GITR and OX40 antibody programs from co-funded development and profit-sharing arrangements to royalty-bearing programs, with Incyte now responsible for global development and commercialization.

Indication Status Update
Epacadostat (IDO1) Unresectable or metastatic melanoma Phase 3 (ECHO-301) in combination with pembrolizumab (PD-1)
NSCLC, renal, bladder and head & neck cancer Phase 3 in combination with pembrolizumab (PD-1) expected to begin in 2017
Multiple tumor types Phase 2 (ECHO-202) expansion cohorts in combination with pembrolizumab (PD-1)
Multiple tumor types Phase 2 (ECHO-204) expansion cohorts in combination with nivolumab (PD-1)
Multiple tumor types Phase 2 (ECHO-203) expansion cohorts in combination with durvalumab (PD-L1)
NSCLC, bladder cancer Phase 1/2 (ECHO-110) dose-escalation in combination with atezolizumab (PD-L1)
INCB01158 (ARG, co-developed with Calithera)
Solid tumors Phase 1/2 dose-escalation
INCSHR1210 (PD-1, licensed from Hengrui)
Solid tumors Phase 1/2 dose-escalation completed; enrollment suspended
INCAGN1876 (GITR) Solid tumors Phase 1/2 dose-escalation
INCAGN1949 (OX40) Solid tumors Phase 1/2 dose-escalation

PD-1 platform study Solid tumors Phase 1/2, pembrolizumab (PD-1) in combination with itacitinib (JAK1) or INCB50465 (PI3Kδ)
JAK1 platform study Solid tumors Phase 1/2, itacitinib (JAK1) in combination with epacadostat (IDO1) or INCB50465 (PI3Kδ)

Non-oncology
A Phase 2 trial of topical ruxolitinib for the treatment of patients with atopic dermatitis has recently been initiated, and a Phase 2 trial in patients with vitiligo is expected to begin during 2017.

Indication Status Update
Topical ruxolitinib (JAK1/JAK2) Alopecia areata, atopic dermatitis Phase 2
Vitiligo Phase 2 expected to begin in 2017

Partnered
In February 2017, the European Commission approved baricitinib – which will be marketed as Olumiant – for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to, one or more disease-modifying antirheumatic drugs (DMARDs). In January 2017, the FDA extended the review period for the new drug application (NDA) for baricitinib by three months to allow time to review additional data analyses submitted by Lilly.
Lilly has announced its intention to initiate a Phase 3 program investigating baricitinib as a treatment for patients with psoriatic arthritis during 2017, and Incyte has opted into co-development in this indication. Incyte has also opted into co-development in axial spondyloarthritis and atopic dermatitis, should Lilly decide to progress into a pivotal program in these indications.
Novartis anticipates submitting an NDA for capmatinib, Incyte’s potent and selective c-MET inhibitor, in 2018.

Indication Status Update
Baricitinib (JAK1/JAK2, licensed to Lilly) Rheumatoid arthritis Approved in Europe; FDA review extended by three months
Psoriatic arthritis Phase 3 expected to begin in 2017
Atopic dermatitis, systemic lupus erythematosus Phase 2
Capmatinib (c-MET, licensed to Novartis) Non-small cell lung cancer, liver cancer Phase 2 in EGFR wild-type ALK negative NSCLC patients with c-MET amplification and mutation

2016 Fourth-Quarter and Full-Year Financial Results
Revenues For the quarter ended December 31, 2016, net product revenues of Jakafi were $238 million as compared to $182 million for the same period in 2015, representing 30 percent growth. For the full year ended December 31, 2016, net product revenues of Jakafi were $853 million as compared to $601 million for the same period in 2015, representing 42 percent growth.
For the quarter and seven month period ended December 31, 2016, net product revenues of Iclusig were $13 million and $30 million, respectively1.
For the quarter and full year ended December 31, 2016, product royalties from sales of Jakavi outside of the United States received from Novartis were $33 million and $111 million, respectively, as compared to $24 million and $75 million, respectively, for the same periods in 2015.
For the quarter and full year ended December 31, 2016, contract revenues were $43 million and $113 million, respectively, as compared to $38 million and $78 million, respectively, for the same periods in 2015. The increase in contract revenues for the full year ended December 31, 2016 relates to milestone payments earned.
For the quarter ended December 31, 2016, total revenues were $326 million as compared to $244 million for the same period in 2015. For the full year ended December 31, 2016, total revenues were $1,106 million as compared to $754 million for the same period in 2015.

Year Over Year Revenue Growth
(in thousands, unaudited)

Three Months Ended Twelve Months Ended
December 31, % December 31, %
2016 2015 Change 2016 2015 Change
Revenues:
Jakafi net product revenue $ 237,531 $ 182,021 30% $ 852,816 $ 601,015 42%
Iclusig net product revenue 12,867 – – 29,588 – –
Product royalty revenues 33,225 23,646 41% 110,711 74,821 48%
Contract revenues 42,869 38,214 – 112,512 77,857 –
Other revenues 6 – – 92 58 –
Total revenues $ 326,498 $ 243,881 34% $ 1,105,719 $ 753,751 47%

Research and development expenses Research and development expenses for the quarter and full year ended December 31, 2016 were $162 million and $582 million, respectively, as compared to $117 million and $480 million, respectively, for the same periods in 2015. Included in research and development expenses for the quarter and full year ended December 31, 2016 were non-cash expenses related to equity awards to our employees of $17 million and $60 million, respectively. The increase in research and development expenses for the full year ended December 31, 2016 was primarily due to the expansion of the Company’s clinical portfolio.
Selling, general and administrative expenses Selling, general and administrative expenses for the quarter and full year ended December 31, 2016 were $96 million and $303 million, respectively, as compared to $52 million and $197 million, respectively, for the same periods in 2015. Included in selling, general and administrative expenses for the quarter and full year ended December 31, 2016 were non-cash expenses related to equity awards to our employees of $10 million and $36 million, respectively. Increased selling, general and administrative expenses are driven primarily by additional costs related to the commercialization of Jakafi and the geographic expansion in Europe.
Change in fair value of acquisition-related contingent consideration The change in fair value of acquisition-related contingent consideration of $7 million and $17 million for the quarter and seven month period ended December 31, 2016 represents the fair market value adjustments of the Company’s contingent liability related to the acquisition of the European business of ARIAD Pharmaceuticals, Inc.
Unrealized loss on long term investment Unrealized loss on long term investment for the quarter and full year ended December 31, 2016 were of $24 million and $3 million, respectively, as compared to $0 million and $5 million, respectively, for the same periods in 2015. The unrealized loss on long term investment represents the fair market value adjustments of the Company’s investment in Agenus.
Net income Net income for the quarter ended December 31, 2016 was $9 million, or $0.05 per basic and diluted share, as compared to net income of $55 million, or $0.30 per basic and $0.29 per diluted share for the same period in 2015. Net income for the full year ended December 31, 2016 was $104 million, or $0.55 per basic and $0.54 per diluted share, as compared to net income of $7 million, or $0.04 per basic and $0.03 per diluted share for the same period in 2015.
Cash, cash equivalents and marketable securities position As of December 31, 2016, cash, cash equivalents and marketable securities totaled $809 million, as compared to $708 million as of December 31, 2015.
2017 Financial Guidance
The Company has provided full year 2017 financial guidance, as detailed below.

Guidance
Jakafi net product revenues $1,020-$1,070 million
Iclusig net product revenues $60-$65 million
Research and development expenses: ongoing $785-$835 million
Research and development expenses: anticipated one-time items* $205 million
Selling, general and administrative expenses $340-$360 million
Change in fair value of acquisition-related contingent consideration $30-$35 million
* One-time items related to the amended Agenus collaboration, and the Merus and Calithera collaborations

On February 14, 2017 Amgen (NASDAQ:AMGN) reported the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for BLINCYTO (blinatumomab) to include overall survival (OS) data from the Phase 3 TOWER study, supporting the conversion of BLINCYTO’s accelerated approval to full approval (Press release, Amgen, FEB 14, 2017, View Source [SID1234517716]). The sBLA also includes new data supporting the treatment of patients with Philadelphia chromosome-positive (Ph+) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The application aims to broaden BLINCYTO’s indication for the treatment of patients with relapsed or refractory B-cell precursor ALL.

BLINCYTO was previously granted breakthrough therapy designation and accelerated approval in December 2014. It is also the first FDA-approved bispecific CD19-directed CD3 T cell engager (BiTE) antibody, and the first single-agent immunotherapy to treat patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL.

“Acute lymphoblastic leukemia is one of the most aggressive B-cell malignancies, and adult patients who relapse or are refractory to treatment often go through multiple lines of therapy,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “We are excited to potentially receive full approval for BLINCYTO, the first immunotherapy to demonstrate an overall survival benefit versus standard of care chemotherapy in patients with relapsed or refractory Ph- B-cell precursor ALL, and bring a much needed new treatment option to those who are Ph+.”

Results from the TOWER study, investigating the efficacy of BLINCYTO versus standard of care (SOC) chemotherapy in adult patients with Ph- relapsed or refractory B-cell precursor ALL, were presented during the Presidential Symposium at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper). BLINCYTO has a BOXED WARNING in its product label regarding Cytokine Release Syndrome (CRS) and Neurological Toxicities.

ALL is a rare and rapidly progressing cancer of the blood and bone marrow.1,2 In adult patients with relapsed or refractory ALL, median OS is just three to five months.3 Currently, there is no broadly accepted standard treatment regimen for adult patients with relapsed or refractory ALL beyond chemotherapy.4 In adult ALL, approximately 75 percent is B-cell precursor ALL, of which 75-80 percent is Ph- and roughly half will be refractory to treatment or experience relapse.5

About the TOWER Study
The TOWER study was a Phase 3, randomized, active-controlled, open-label study investigating the efficacy of BLINCYTO versus SOC chemotherapy in 405 adult patients with Ph- relapsed or refractory B-cell precursor ALL. The study enrolled a difficult-to-treat patient population which included patients from several stages of relapse, 17 percent of whom had relapsed post-allogenic stem cell transplant (alloSCT), and excluded those with late first relapse (≥ 12 months after initial remission). Patients were randomized in a 2:1 ratio to receive BLINCYTO (n=271) or treatment with investigator choice of one of four protocol-defined SOC chemotherapy regimens (n=134). The primary endpoint was OS. Key secondary endpoints included complete remission within 12 weeks, the combined endpoint of complete remission plus complete remission with partial or incomplete hematologic recovery and event-free survival. Other secondary endpoints included remission duration, minimal residual disease (MRD) remission (<10–4), alloSCT rate and adverse event rates. The TOWER study is the confirmatory trial for BLINCYTO. Click here to read about the trial on ClinicalTrials.gov. About the ALCANTARA Study The ALCANTARA study was a Phase 2, single-arm, multicenter, open-label study investigating the efficacy and tolerability of BLINCYTO in 45 adult patients with Ph+ B-cell precursor ALL who had relapsed after or were refractory to at least one second or later (2+)-generation tyrosine kinase inhibitor (TKI), or were intolerant to 2+-generation TKI and intolerant or refractory to imatinib. BLINCYTO was administered in 28-day cycles by continuous intravenous infusion. The primary endpoint was complete remission or complete remission with partial hematologic recovery during the first two cycles. Key secondary endpoints included MRD response, rate of allogeneic hematopoietic stem cell transplantation (alloHSCT), relapse-free survival, OS and adverse events. 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 and priority review designations by the FDA, and is now approved in the U.S. for the treatment of Ph- relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials. In November 2015, BLINCYTO was granted conditional marketing authorization in the EU for the treatment of adults with Ph- relapsed or refractory B-cell precursor ALL. About BiTE Technology Bispecific T cell engager (BiTE) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body's immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com. 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 with a median time to onset of 3 days. In patients receiving BLINCYTO, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 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.a