On February 14, 2018 Amgen (NASDAQ:AMGN) reported that the Oncologic Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) will review data supporting the BLINCYTO (blinatumomab) supplemental Biologics License Application (sBLA) for the treatment of patients with minimal residual disease (MRD)-positive B-cell precursor acute lymphoblastic leukemia (ALL) at a meeting on March 7, 2018 (Press release, Amgen, FEB 14, 2018, View Source;p=RssLanding&cat=news&id=2332494 [SID1234523963]).

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MRD refers to the presence of a small amount of detectible cancer cells that remain in the patient after treatment.

"After achieving remission, the presence of MRD is the strongest prognostic factor for relapse in acute lymphoblastic leukemia. However, today up to half of patients remain MRD-positive after induction treatments and receive limited clinical benefit from treatments like chemotherapy or stem cell transplantation as a result of failure to identify and treat this residual disease," said David M. Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. "Currently there are no approved therapies for patients with MRD-positive ALL, representing a significant unmet need. This sBLA for BLINCYTO is the first application to ever be submitted for an MRD positive indication, and we look forward to discussing the supporting data with members of the Committee."

The Committee will review results from clinical studies in support of this potential new indication, including results from the Phase 2 BLAST study evaluating patients with B-cell precursor ALL and persistent or recurrent MRD after at least three cycles of intensive chemotherapy.

BLINCYTO is the first-and-only approved bispecific CD19-directed CD3 T cell engager (BiTE) immunotherapy. It is also the first bispecific antibody construct from Amgen’s BiTE platform, which helps the body’s immune system target cancer cells and represents an entirely new area of oncology research.

The sBLA for BLINCYTO was accepted by the FDA for priority review, and a Prescription Drug User Fee Act (PDUFA) target action date of March 29, 2018 has been set.

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 in 2014 for the treatment of relapsed or refractory B-cell precursor ALL in adults and children, and is now approved in the U.S. for this indication.

In November 2015, BLINCYTO was granted conditional marketing authorization in the European Union for the treatment of adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL. Additional regulatory applications for BLINCYTO are underway and have been submitted to health authorities worldwide.

About the BLAST Study
The BLAST study is the largest prospective trial in patients with MRD-positive ALL. It is an open-label, multicenter, confirmatory single-arm, Phase 2 study evaluating the efficacy, safety and tolerability of BLINCYTO in adult patients with MRD-positive B-cell precursor ALL in complete hematologic remission after three or more cycles of intensive chemotherapy treatments and a presence of MRD. Patients received continuous IV infusion of 15 μg/m2/d for four weeks, followed by two weeks off. Patients received up to four cycles of treatment, or could undergo a hematopoietic stem cell transplantation (HSCT) at any time after the first cycle, if eligible. The primary endpoint was the rate of complete MRD response within the first treatment cycle. The key secondary endpoint was relapse-free survival at 18 months. Additional secondary endpoints include incidence and severity of adverse events, overall survival (OS), time to hematological remission and duration of complete MRD response. Results from the BLAST study were presented at the 57th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper) in 2015.

About ALL and MRD
ALL is a rare and rapidly progressing cancer of the blood and bone marrow that occurs in both adults and children.1,2 Many adult patients with ALL relapse, often within one year of their diagnosis, from which the median survival is only 4 to 8 months.3 Poor outcomes have been observed in patients who relapse after achieving a complete response but have persistent MRD, with 5-year OS rates as high as 75 percent for patients that achieve MRD-negative status, compared with 33 percent among patients that remain MRD-positive.4 In pediatric patients, MRD-positive status after treatment is associated with a 15-times higher risk of relapse compared with those with undetectable residual disease.5

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 bridge T cells to tumor cells, using the patient’s own immune system to eradicate their cancer. 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

Indication and Important Safety Information, including Boxed WARNINGS, for BLINCYTO (blinatumomab) for injection, for intravenous use

INDICATION

BLINCYTO is indicated for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children.

IMPORTANT SAFETY INFORMATION

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 65% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. The median time to the first event was within the first 2 weeks of BLINCYTO treatment and the majority of events resolved. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. 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 19 days. Grade 3 or greater elevations in liver enzymes occurred in 7% 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.
Risk of Serious Adverse Reactions in Pediatric Patients due to Benzyl Alcohol Preservative: Serious and fatal adverse reactions including "gasping syndrome," which is characterized by central nervous system depression, metabolic acidosis, and gasping respirations, can occur in neonates and infants treated with benzyl alcohol-preserved drugs including BLINCYTO (with preservative). When prescribing BLINCYTO (with preservative) for pediatric patients, consider combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO (with preservative) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known. Due to the addition of bacteriostatic saline, 7-day bags of BLINCYTO solution for infusion with preservative contain benzyl alcohol and are not recommended for use in any patients weighing < 22 kg.
Adverse Reactions

The most common adverse reactions in Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL (TOWER Study) (≥ 20%) in the BLINCYTO arm were infections (bacterial and pathogen unspecified), pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, and neutropenia. Serious adverse reactions were reported in 62% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, sepsis, pneumonia, overdose, septic shock, CRS, bacterial sepsis, device related infection, and bacteremia.
Adverse reactions that were observed more frequently (≥ 10%) in the pediatric population compared to the adult population were pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%), infusion-related reaction (49% vs. 34%), thrombocytopenia (34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17% vs. 6%).
In pediatric patients less than 2 years old (infants), the incidence of neurologic toxicities was not significantly different than for the other age groups, but its manifestations were different; the only event terms reported were agitation, headache, insomnia, somnolence, and irritability. Infants also had an increased incidence of hypokalemia (50%) compared to other pediatric age cohorts (15-20%) or adults (17%).
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.

About Amgen’s Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen’s supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.

On February 14, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, today reported business highlights and financial results for the fourth quarter and year ended December 31, 2017 (Press release, Agios Pharmaceuticals, FEB 14, 2018, View Source [SID1234523961]). In addition, Agios highlighted select 2018 corporate milestones and data presentations for its clinical development programs.

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"2017 was an extraordinary year for Agios with the U.S. approval of IDHIFA, our first internally discovered and developed drug, the NDA submission for our wholly owned medicine ivosidenib and our sixth IND submission since the company’s inception," said David Schenkein, M.D., chief executive officer at Agios. "It was a data-rich year where we set the stage for building long-term value across our cancer and rare disease portfolios. Execution in 2018 will be equally critical as we ready our organization for the potential approval and launch of ivosidenib, initiate our pivotal program for AG-348 in pyruvate kinase deficiency and advance our robust discovery portfolio."

KEY UPCOMING MILESTONES

The company plans to achieve the following key milestones in 2018:

Cancer:

Potential approval and commercialization of ivosidenib in the United States for relapsed/refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase-1 (IDH1) mutation in the third quarter of 2018.
Potential submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for ivosidenib for IDH1m R/R AML in the fourth quarter of 2018.
Support, in conjunction with Celgene, the initiation of an intergroup sponsored, global, registration-enabling Phase 3 trial combining ivosidenib or enasidenib with standard induction and consolidation chemotherapy in frontline AML patients with an IDH1 or IDH2 mutation in the fourth quarter of 2018.
Initiate a perioperative ‘window’ trial with ivosidenib and AG-881 in low-grade glioma in the first quarter of 2018 to further investigate their effects on brain tumor tissue.
Initiate a Phase 1 dose-escalation trial for AG-270, a first-in-class methionine adenosyltransferase 2a (MAT2A) inhibitor, in patients with methylthioadenosine phosphorylase (MTAP)-deleted tumors in the first quarter of 2018.
Rare Genetic Diseases:

Initiate two global pivotal trials for AG-348 in pyruvate kinase (PK) deficiency in the first half of 2018:
ACTIVATE-T: A single arm trial of approximately 20 regularly transfused patients is expected to initiate in the first quarter of 2018.
ACTIVATE: A placebo-controlled trial of approximately 80 patients who do not receive regular transfusions is expected to initiate in the second quarter of 2018.
Initiate a global registry, known as PEAK, for adult and pediatric patients with PK deficiency in the first quarter of 2018.
Initiate a Phase 2 proof of concept trial of AG-348 in thalassemia in the fourth quarter of 2018.
Research:

Submit an investigational new drug (IND) application for our newest development candidate, an inhibitor of the metabolic enzyme dihydroorotate dehydrogenase (DHODH) for the treatment of hematologic malignancies in the fourth quarter of 2018.
ANTICIPATED KEY 2018 DATA PRESENTATIONS

Updated data from the expansion phase of the ongoing Phase 1 study of ivosidenib in IDH1m R/R AML has been submitted to the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
Updated data from the ongoing Phase 1/2 combination trial of enasidenib or ivosidenib with VIDAZA in patients with newly diagnosed AML with an IDH2 or IDH1 mutation ineligible for intensive chemotherapy has been submitted to ASCO (Free ASCO Whitepaper).
First clinical data from the Phase 1 study of AG-881 in advanced IDHm positive solid tumors, including glioma, has been submitted to ASCO (Free ASCO Whitepaper).
Updated data from the ongoing Phase 1 combination trial of enasidenib or ivosidenib with standard-of-care intensive chemotherapy in patients with newly diagnosed AML with an IDH2 or IDH1 mutation to be submitted to the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.
FOURTH QUARTER 2017 HIGHLIGHTS & RECENT PROGRESS

Completed an underwritten public offering in January of 8,152,986 shares of common stock at the offering price of $67.00 per share, resulting in proceeds, net of underwriting discounts and commissions, of approximately $516.2 million.
Submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for ivosidenib for the treatment of patients with R/R AML with an IDH1 mutation.
Received FDA clearance of an IND application for AG-270, a MAT2A inhibitor, for the treatment of MTAP-deleted tumors.
Presented new and updated data from the IDH and PKR programs at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH) (Free ASH Whitepaper):
First data from the expansion phase of the ongoing Phase 1 trial of ivosidenib in IDH1m R/R AML and advanced hematologic malignancies
First data from the ongoing Phase 1 combination trial of ivosidenib or enasidenib with standard-of-care intensive chemotherapy in patients with newly diagnosed AML with an IDH1 or IDH2 mutation
First data from the ongoing Phase 1/2 combination trial of ivosidenib or enasidenib with VIDAZA in patients with newly diagnosed AML with an IDH1 or IDH2 mutation ineligible for intensive chemotherapy
Updated data from the AG-348 Phase 2 DRIVE PK study in PK deficiency
Appointed Jacqualyn "Jackie" Fouse, Ph.D., former president and chief financial officer of Celgene, to Agios’ board of directors.
Presented updated data from the glioma expansion cohort of the ongoing Phase 1 trial of ivosidenib in advanced IDH1m positive solid tumors at the 2017 Society for NeuroOncology Annual Meeting.
FULL YEAR 2017 FINANCIAL RESULTS

Cash, cash equivalents and marketable securities as of December 31, 2017 were $567.8 million, compared to $573.6 million as of December 31, 2016. The decrease in cash was driven by expenditures to fund operations of $306.8 million during the year ended December 31, 2017. These expenditures were offset by an increase in cash driven by net proceeds of $270.2 million from the April follow on offering, $17.0 million of cost reimbursements under our collaboration agreements with Celgene and $14.2 million received from employee stock transactions.

Revenue for the year ended December 31, 2017 was $43.0 million, which includes $41.1 million of collaboration revenue and $1.9 million of royalty revenue from net sales of IDHIFA. Revenue for the year ended December 31, 2016 was $69.9 million, which included a $25.0 million milestone payment related to the initiation of the Phase 3 IDHENTIFY trial with IDHIFA under the 2010 Agreement.

Research and development (R&D) expenses were $292.7 million, including $30.8 million of stock-based compensation expense, for the year ended December 31, 2017, compared to $220.2 million, including $25.4 million in stock-based compensation expense, for the year ended December 31, 2016. The increase in R&D expense was primarily attributable to the ivosidenib program, including manufacturing and regulatory activities to prepare the NDA submission, start-up costs for the Phase 3 AGILE clinical trial, and on-going site activation and patient enrollment of the Phase 3 ClarIDHy clinical trial. R&D expense also increased compared to the prior year due to IND enabling activities for AG-270.

General and administrative (G&A) expenses were $71.1 million, including $17.0 million of stock-based compensation expense, for the year ended December 31, 2017, compared to $50.7 million, including $16.7 million of stock-based compensation expense, for the year ended December 31, 2016. The increase in G&A expense was primarily attributable to an increase of $21.1 million to support our growing commercial organization for the launch of IDHIFA and the potential launch of ivosidenib in 2018.

Net loss for the year ended December 31, 2017 was $314.7 million, compared to a net loss of $198.5 million for the year ended December 31, 2016.

CASH GUIDANCE

In January, Agios completed an underwritten public offering of 8,152,986 shares of common stock, which includes the full exercise of the underwriters’ option to purchase an additional 1,063,433 shares, at the offering price of $67.00 per share, resulting in proceeds, net of underwriting discounts and commissions, of approximately $516.2 million.

The company expects that its cash, cash equivalents and marketable securities as of December 31, 2017, together with the net proceeds from the recent financing, anticipated product and royalty revenue, anticipated interest income, and anticipated expense reimbursements, but excluding any additional program-specific milestone payments, will enable the company to fund its anticipated operating expenses and capital expenditure requirements through at least the end of 2020.

CONFERENCE CALL INFORMATION

Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss fourth quarter and full year 2017 financial results and recent business activities. To participate in the conference call, please dial 1-877-377-7098 (domestic) or 1-631-291-4547 (international) and referring to conference ID 3198522. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

On February 14, 2018 Athenex, Inc. (Nasdaq:ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported early completion of patient enrollment for both Phase III clinical studies of KX2-391 Ointment for actinic keratosis indications months ahead of schedule (Press release, Athenex, FEB 14, 2018, View Source;p=RssLanding&cat=news&id=2332390 [SID1234523964]).

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Actinic keratosis is a common skin condition that is induced through ultra-violet light damage, resulting in patches of thick, scaly, or crusty skin. Left untreated, the lesions have risk of progression to squamous cell carcinoma and consequently treatment by a dermatologist is recommended. Actinic keratosis is the most common pre-cancerous condition in dermatology and it affects more than 55 million Americans. Actinic keratosis constitutes between 14-29% of dermatologist visits in the USA.1

KX2-391, also known as KX-01, is a dual Src kinase and tubulin polymerization inhibitor and a first-in-class topical treatment of actinic keratosis. Phase I and Phase II clinical studies showed excellent efficacy and safety results. After the FDA end of Phase II meeting, two randomized double-blind controlled Phase III trials totaling 600 patients were initiated in September 2017 in the United States and completed patient recruitment in February 2018.

Dr. Rudolf Kwan, Athenex’s Chief Medical Officer, commented, "KX2-391 ointment, given its excellent clinical efficacy and safety profile compared to existing medical therapy, has the potential to change the paradigm of topical therapy for actinic keratosis. We are delighted to see that our investigators and patients are also seeing the potential of this new treatment as indicated by the rapid completion of patient enrollment in around four months which is extremely fast, and three months ahead of our original schedule. Such rapid patient recruitment rates in clinical trials underscores the excitement of the clinical and scientific communities."

Dr. Johnson Lau, Athenex’s Chief Executive Officer and Chairman of the Board, stated, "This excellent milestone highlights the quality of our clinical team members and operation. Our previous commitment to build an internal clinical operation will also ensure that the clinical trial monitoring and management, database management, and biostatistics will not be dependent on outside vendors. As such, we are confident that all aspects of treatment, follow up, monitoring, and database will be completed on time. We are now expecting topline data to be available in third quarter of 2018. We also look forward to presenting our Phase II data to the public in the upcoming American Academy of Dermatology meeting on February 17, 2018."

As previously announced on December 11, 2017, Athenex and Almirall, a leading skin-health focused global pharmaceutical company and one of the leaders in the field of actinic keratosis treatment, entered into a License Agreement in which Athenex granted Almirall an exclusive license under the Athenex Intellectual Property to research, develop and commercialize KX2-391 in the United States of America and European countries, including Russia. Athenex will receive an upfront fee and near-term payments of up to USD $55 million, and additional indications milestones payment and a royalty payment starting at 15% based on annual net sales, with incremental increases in royalty rates with increased sales. Athenex retains certain co-promotion rights in the USA and retains the rights for other parts of the world including Canada, Central and South America, Japan, Asia and China, Australia and New Zealand, and Africa including South Africa. Almirall will employ its expertise to support the development in Europe and also to commercialize the product in the defined territories. Milestones were established to encourage the joint effort of Athenex and Almirall to develop additional indications and additional formulations.

Peter Guenter, Chief Executive Officer at Almirall, said, "We are impressed by the Athenex team in their execution of drug development. KX2-391, given its efficacy and very good safety profile compared to existing medical therapies, has the potential to change the standard of care for actinic keratosis, as well as expand the market since many patients remain undiagnosed or untreated. Almirall’s experience in Europe, currently as leaders in actinic keratosis, and our presence in the United States will help to develop and commercialize this product. We are now expecting top line Phase III data to be available in the third quarter of 2018. We also look forward to the presentation of the Phase II data to the public in the upcoming American Academy of Dermatology meeting on February 17, 2018."

References
1. E. Stockfleth et al. Physician perceptions and experience of current treatment in actinic keratosis. JEADV 2015, 29, 298–306

On February 13, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, "Astellas") and Universal Cells, Inc. (CEO: Claudia Mitchell, "Universal Cells") reported that Astellas has acquired Universal Cells (Press release, Astellas, FEB 14, 2018, View Source [SID1234649901]). Astellas will gain Universal Cells’ proprietary Universal Donor Cell technology to create cell therapy products that do not require Human Leukocyte Antigen (HLA) matching, potentially overcoming a huge treatment challenge by reducing the risk of rejection.

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In October 2017, the Astellas Institute for Regenerative Medicine (AIRM) and Universal Cells entered into an exclusive license agreement to utilize Universal Donor Cell technology in a single indication. Today’s acquisition enables Astellas to fully utilize this proprietary technology in even more therapeutic areas. The acquisition combines Astellas’ capability of establishing differentiated functional cells from pluripotent stem cells with Universal Cell’s ability to produce pluripotent stem cells that have lower immunological rejection to further enable investigation of innovative cell therapy treatments for various diseases that currently have few or no treatment options.

"We have been very impressed with Universal Cells’ capabilities in cell therapy, including Universal Donor Cell technology, which led us to our initial collaboration and ultimately this acquisition," commented Yoshihiko Hatanaka, President and CEO, Astellas. "This additional capability will further enable Astellas to develop potential innovative cell therapies for numerous diseases with high unmet medical needs."

"We are thrilled to be able to leverage the full potential of our Universal Donor Cell technology by becoming an intrinsic part of Astellas’ effort to fulfill the promises of Regenerative Medicine to treat diseases," said Claudia Mitchell, CEO of Universal Cells. "The acquisition represents the recognition of the immense potential of our unique technology and of the outstanding work done by our team at Universal Cells."

Astellas will pay up to $102.5 million of upfront and milestones to acquire 100 percent ownership of Universal Cells depending on achievement of certain specified clinical milestones.

Universal Cells has become a wholly-owned subsidiary of Astellas following the close of the acquisition.

The impact of this transaction on Astellas’ financial results for the fiscal year ending

March 31, 2018 will be immaterial.

On February 14, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the U.S. Food and Drug Administration (FDA) has approved ERLEADA (apalutamide), a next-generation androgen receptor inhibitor,1 for the treatment of patients with non-metastatic castration-resistant prostate cancer (NM-CRPC) (Press release, Johnson & Johnson, FEB 14, 2018, View Source [SID1234523973]). ERLEADA is the first FDA-approved treatment for these patients. Today’s approval follows an FDA Priority Review designation based upon data from the Phase 3 SPARTAN study, which demonstrated a 72 percent reduction in risk of distant metastasis or death, and an increase in median metastasis-free survival (MFS) by more than two years (difference of 24.31 months) in patients with NM-CRPC.

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"The need to delay metastasis is critical to the treatment of prostate cancer. Nearly 90 percent of patients with castration-resistant prostate cancer will eventually develop bone metastases, at which point the prognosis sharply worsens," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. "We are excited about what this approval means for patients living with prostate cancer, and that physicians now have an important and much-needed treatment option that has been shown to delay the progression of castration-resistant prostate cancer."

ERLEADA received FDA approval based on the Phase 3 data from the SPARTAN clinical trial, which assessed the efficacy and safety of ERLEADA versus placebo in patients with NM-CRPC who had a rapidly rising PSA while receiving continuous androgen deprivation therapy.2 The study was recently presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) on Thursday, February 8, 2018 in San Francisco and published in The New England Journal of Medicine.2,3

"The SPARTAN trial results demonstrated impressive clinical benefits in patients with non-metastatic castration-resistant prostate cancer," said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program at the Massachusetts General Hospital Cancer Center, Professor of Medicine at Harvard Medical School, and co-principal investigator of the SPARTAN study. "As an oncologist and clinical investigator, I know how devastating it can be for patients and their families to hear that the cancer has spread. With this approval, doctors now have the chance to offer hope for delaying metastases in patients with castration-resistant prostate cancer."

"As the impact of prostate cancer continues to grow, we are reminded every day of the critical need for therapeutic options that offer patients with prostate cancer more time with their loved ones," Mark Scholz, M.D., Executive Director of the Prostate Cancer Research Institute. "Today’s approval is significant, as it means that patients with non-metastatic castration-resistant prostate cancer now have a treatment option that offers renewed hope."

SPARTAN, a Phase 3, randomized, double-blind, placebo-controlled, multi-center study, enrolled 1,207 patients with non-metastatic castration-resistant prostate cancer.4 Patients were randomized 2:1 to receive either ERLEADA orally at a dose of 240 mg once daily (n=806), or placebo once daily (n=401).4 All patients in the SPARTAN trial received a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy.4

ERLEADA decreased the risk of distant metastasis or death by 72 percent compared to placebo (HR = 0.28; 95% CI, 0.23-0.35; P<0.0001).4 The median MFS was 40.51 months for ERLEADA compared to 16.20 months for placebo, prolonging MFS by more than two years (difference of 24.31 months).4 MFS benefit was consistently seen across patient subgroups including prostate specific antigen doubling time (PSADT) (≤6 months or >6 months), use of a prior bone-sparing agent (yes or no), and locoregional disease (N0 or N1).4

The major efficacy outcome was supported by statistically significant improvements for the following secondary endpoints: time to metastasis (TTM), progression-free survival (PFS) and time to symptomatic progression.4 The median TTM was 40.51 months for ERLEADA compared to 16.59 months for placebo (HR=0.27; 95% CI, 0.22-0.34; P<0.0001) and the median PFS was 40.51 months compared to 14.72 months for placebo (HR=0.29; 95% CI, 0.24-0.36; P<0.0001).4 Overall survival data were not mature at the time of final MFS analysis (24% of the required number of events).4

Warnings and Precautions include seizure, falls and fractures.4 In the SPARTAN trial, the most common adverse reactions (≥10%) were fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.4

About Non-Metastatic Castration-Resistant Prostate Cancer
Non-metastatic castration-resistant prostate cancer (NM-CRPC) refers to a disease state when the cancer no longer responds to medical or surgical treatments that lower testosterone, but has not yet been discovered in other parts of the body using a total body bone scan or CT scan.5 Features include: lack of detectable metastatic disease;5 rapidly rising prostate-specific antigen while on androgen deprivation therapy (ADT) and serum testosterone level below 50 ng/dL.6,7 Ninety percent of patients with CRPC will eventually develop bone metastases, which can lead to pain, fractures and spinal cord compression.8 The relative 5-year survival rate for patients with distant stage prostate cancer is 30 percent.9 It is critical to delay the onset of metastasis in patients with NM-CRPC.

About ERLEADA
ERLEADA (apalutamide) is an androgen receptor (AR) inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.4

ERLEADA is an AR inhibitor that binds directly to the ligand-binding domain of the AR. ERLEADA inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription.4 A major metabolite, N-desmethyl apalutamide, is a less potent inhibitor of AR, and exhibited one-third the activity of ERLEADA in an in vitro transcriptional reporter assay.4 ERLEADA administration caused decreased tumor cell proliferation and increased apoptosis leading to decreased tumor volume in mouse xenograft models of prostate cancer.4

Full prescribing information will be available soon at www.ERLEADA.com.

Important Safety Information4

CONTRAINDICATIONS

Pregnancy – ERLEADA can cause fetal harm and potential loss of pregnancy.

WARNINGS AND PRECAUTIONS

Falls and Fractures – In the SPARTAN study, falls and fractures occurred in 16% and 12% of patients treated with ERLEADA compared to 9% and 7% treated with placebo respectively. Falls were not associated with loss of consciousness or seizure. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone targeted agents.

Seizure – In a randomized study (SPARTAN), two patients (0.2%) treated with ERLEADA experienced a seizure. Permanently discontinue ERLEADA in patients who develop a seizure during treatment. It is unknown whether anti-epileptic medications will prevent seizures with ERLEADA. Advise patients of the risk of developing a seizure while receiving ERLEADA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others.

ADVERSE REACTIONS

Adverse Reactions – The most common adverse reactions (≥10%) were fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.

Laboratory Abnormalities

Hematology: anemia ERLEADA 70% (Grade 3-4 0.4%) placebo 64% (Grade 3-4 0.5%) leukopenia ERLEADA 47% (Grade 3-4 0.3%) for, placebo 29% (Grades 3-4 0%), lymphopenia ERLEADA 41% (Grade 3-4 2%), placebo 21% (Grade 3-4 2%);
Chemistry – hypercholesterolemia ERLEADA 76%(Grade3-4 0.1%), placebo 46% (Grade 3-4 0%); hypertriglycemia ERLEADA 70%(Grade 3-4 2%) Placebo 59% (0.8%); hypertriglyceridemia ERLEADA 67%(Grade 3-4 2%) placebo 49%(Grade 3-4 0.8%); Hyperkalemia ERLEADA 32%(Grade 3-4 2%) Placebo 22%(Grade 3-4 0.5%)
Rash – Rash was most commonly described as macular or maculo-papular. Adverse reactions were 24% with ERLEADA versus 6% with placebo. Grade 3 rashes (defined as covering > 30% body surface area [BSA]) were reported with ERLEADA treatment (5%) versus placebo (0.3%).

The onset of rash occurred at a median of 82 days. Rash resolved in 81% of patients within a median of 60 days (range: 2 to 709 days) from onset of rash. Four (4%) of patients treated with ERLEADA received systemic corticosteroids. Rash recurred in approximately half of patients who were re-challenged with ERLEADA.

Hypothyroidism – Hypothyroidism was reported for 8% of patients treated with ERLEADA and 2% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. Elevated TSH occurred in 25% of patients treated with ERLEADA and 7% of patients treated with placebo. The median onset was Day 113. There were no Grade 3 or 4 adverse reactions. Thyroid replacement therapy, when clinically indicated, should be initiated or dose-adjusted.

Effect of Other Drugs on ERLEADA – Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state exposure of the active moieties. No initial dose adjustment is necessary however, reduce the ERLEADA dose based on tolerability [see Dosage and Administration (2.2)].

DRUG INTERACTIONS

Effect of ERLEADA on Other Drugs – ERLEADA is a strong inducer of CYP3A4 and CYP2C19, and a weak inducer of CYP2C9 in humans. Concomitant use of ERLEADA with medications that are primarily metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower exposure to these medications. Substitution for these medications is recommended when possible or evaluate for loss of activity if medication is continued. Concomitant administration of ERLEADA with medications that are substrates of UDP-glucuronosyl transferase (UGT) can result in decreased exposure. Use caution if substrates of UGT must be co-administered with ERLEADA and evaluate for loss of activity.

P-gp, BCRP or OATP1B1 substrates – Apalutamide is a weak inducer of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1) clinically. Concomitant use of ERLEADA with medications that are substrates of P-gp, BCRP, or OATP1B1 can result in lower exposure of these medications. Use caution if substrates of P-gp, BCRP or OATP1B1 must be co-administered with ERLEADA and evaluate for loss of activity if medication is continued.