Varian Halcyon Treatment System Receives China NMPA Approval

On November 28, 2018 Varian (NYSE: VAR) reported its Halcyon system has been approved by the China National Medical Product Administration (NMPA), which allows the company to market this new cancer treatment system in China (Press release, Varian Medical Systems, NOV 28, 2018, View Source [SID1234531710]). This approval further expands the global availability of Halcyon and access to high-quality, cost-effective cancer treatments.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As an advanced cancer treatment system with a human-centered and user-friendly design, Halcyon is engineered to revolutionize clinical workflow, accelerate installation timeframes, expedite commissioning, simplify training, and automate treatment. The system is well suited to treat cancer patients with radiotherapy, offering advanced treatments for lung, prostate, breast, head & neck, and many other forms of cancer.

"We are very excited to further expand the Halcyon system’s global availability," said Chris Toth, president Varian Oncology Systems. "With the most recent announcement by the Chinese government for expanding Category B licenses and enabling County hospital oncology services availability, Halcyon is a perfect fit."

Halcyon has already received FDA 510(k) clearance in the US, CE mark in Europe, Shonin approval in Japan, ANVISA registration in Brazil, Atomic Energy Regulatory Board (AERB) Certificate for Import and Supply as well as Type Approval in India and TFDA approval in Taiwan since its launch in May 2017.

XOSPATA® (gilteritinib) Approved by U.S. FDA for Adult Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) with a FLT3 Mutation

On November 29, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D. "Astellas") reported that the U.S. Food and Drug Administration (FDA) approved XOSPATA (generic name: gilteritinib) for the treatment of adult patients who have relapsed or refractory (resistant to treatment) Acute Myeloid Leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test.2 XOSPATA is an oral therapy and the first and only FLT3-targeting therapy to be approved by the FDA for this population (Press release, Astellas, NOV 28, 2018, View Source [SID1234531692]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Experience the interactive Multichannel News Release here: View Source

The American Cancer Society estimates that in 2018, approximately 19,000 people will be diagnosed with AML in the U.S.3 AML has been associated with various genetic mutations. XOSPATA has demonstrated inhibitory activity against two different mutations, FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain (TKD).2 Impacting approximately 30 percent of AML patients,4 the FLT3-ITD mutation is associated with worsened disease free survival and overall survival.5,6 FLT3-TKD mutations impact approximately 7 percent of AML patients4 and, although the impact of these mutations is less clear,7 they have been associated with treatment resistance.8

"Our ability to use precision medicine to help patients with FLT3-mutated AML takes an important step forward with the approval of XOSPATA," said Alexander Perl, M.D., Abramson Cancer Center, University of Pennsylvania. "There is an urgent need in the clinic for more targeted agents to help patients whose disease is either refractory to the initial therapy, or who have relapsed."

"XOSPATA offers new hope to patients for whom the treatment path forward is unclear," said Steven Benner, M.D., senior vice president and global therapeutic area head, Oncology Development, Astellas. "For the first time, people with relapsed or refractory FLT3 mutation-positive AML have an FDA approved FLT3-targeting treatment available to them. The approval of XOSPATA is also a proud, landmark moment for our oncology program and marks the first approval of a medicine that will be the cornerstone of our new presence in blood cancers."

The FDA’s approval of XOSPATA was based on the interim analysis of the following endpoints in the ADMIRAL clinical trial: the rate of complete remission (CR)/complete remission with partial hematologic recovery (CRh); the duration of CR/CRh (DOR); and the rate of conversion from transfusion dependence to transfusion independence. The CR/CRh rate was 21%. The median duration of CR/CRh was 4.6 months. The rate of conversion from transfusion dependence to transfusion independence was 31.1% for any 56 day post-baseline period. For patients who achieved a CR/CRh, the median time to first response was 3.6 months (range, 0.9 to 9.6 months). The CR/CRh rate was 29 of 126 in patients with FLT3-ITD or FLT3-ITD/TKD and 0 of 12 in patients with FLT3-TKD only.

Full results from the ADMIRAL trial will be submitted for presentation at an upcoming medical meeting.

The safety evaluation of XOSPATA was based on 292 patients with relapsed or refractory AML treated with 120 mg gilteritinib daily. The median duration of exposure to XOSPATA was 3 months (range 0.1 to 42.8 months). The most frequent non-hematological serious adverse reactions (≥5%) reported in patients were pneumonia (19%), sepsis (13%), fever (13%), dyspnea (7%) and renal impairment (5%). Overall, 22 of 292 patients (8%) discontinued XOSPATA treatment permanently due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were pneumonia (2%), sepsis (2%) and dyspnea (1%). The most common adverse reactions (≥20%) were myalgia/arthralgia (42%), transaminase increased (41%), fatigue/malaise (40%), fever (35%), non-infectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%) and vomiting (20%).

Previously, XOSPATA was granted both Orphan Drug designation9 and Fast Track10 designation by the U.S. FDA. Gilteritinib also received Orphan Designation from the European Commission (EC)11 and Orphan Drug Designation from the Japan Ministry of Health, Labor and Welfare (MHLW).12 The MHLW also granted SAKIGAKE designation to gilteritinib for FLT3mut+ relapsed/refractory AML and approved the treatment for this population in September 2018.13

Astellas reflected the impact from this approval in its financial forecast of the current fiscal year ending March 31, 2019.

About XOSPATA
XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory Acute Myeloid Leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.2

XOSPATA was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and potentially commercialize XOSPATA.

Important Safety Information

Contraindications
XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials.

Warnings and Precautions
Posterior Reversible Encephalopathy Syndrome (PRES) There have been rare reports of PRES with symptoms including seizure and altered mental status with XOSPATA. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XOSPATA in patients who develop PRES.

Prolonged QT Interval XOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). Of the 292 patients treated with XOSPATA in the clinical trial, 1.4% were found to have a QTc interval greater than 500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation of treatment with XOSPATA, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration.

Pancreatitis There have been rare reports of pancreatitis in patients receiving XOSPATA in clinical studies. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis.

Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, XOSPATA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 6 months after the last dose of XOSPATA. Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

Adverse Reactions
The most frequent non-hematological serious adverse reactions (≥5%) reported in patients were pneumonia (19%), sepsis (13%), fever (13%), dyspnea (7%) and renal impairment (5%).

Overall, 22 of 292 patients (8%) discontinued XOSPATA treatment permanently due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were pneumonia (2%), sepsis (2%) and dyspnea (1%). The most common adverse reactions (≥20%) were myalgia/arthralgia (42%), transaminase increased (41%), fatigue/malaise (40%), fever (35%), non-infectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%) and vomiting (20%).

Other clinically significant adverse reactions occurring in ≤10% of patients included: electrocardiogram QT prolonged (7%), cardiac failure (grouped terms) (4%), pericardial effusion (3%), pericarditis (2%), differentiation syndrome (1%), anaphylactic reaction (1%) and posterior reversible encephalopathy syndrome (1%).

Lab Abnormalities: The most common lab abnormalities (>20%) that were Grade ≥3 that occurred ≥10% were: hypophosphatemia (12%), alanine aminotransferase increased (12%), hyponatremia (12%), aspartate aminotransferase increased (10%).

Drug Interactions
Combined P-gp and Strong CYP3A Inducers: Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases XOSPATA exposure which may decrease XOSPATA efficacy. Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers.

Strong CYP3A inhibitors: Concomitant use of XOSPATA with a strong CYP3A inhibitor increases XOSPATA exposure. Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity.

Drugs that Target 5HT2B Receptor or Sigma Nonspecific Receptor: Concomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient.

Specific Populations
Lactation: Advise women not to breastfeed during treatment with XOSPATA and for 2 months after the last dose.

Please see Full Prescribing Information for additional safety information.

About the ADMIRAL Trial14
The Phase 3 ADMIRAL trial (NCT02421939) was an open-label, multicenter, randomized study of gilteritinib versus salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy. The primary endpoints of the trial are Overall Survival (OS) and complete remission/complete remission with partial hematologic recovery (CR/CRh) rates. The study enrolled 371 patients with FLT3 mutations present in bone marrow or whole blood, as determined by central lab. Subjects were randomized in a 2:1 ratio to receive gilteritinib (120 mg15) or salvage chemotherapy.

FDA approves treatment for adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a certain genetic mutation

On November 28, 2018 The U.S. Food and Drug Administration reported that it approved Xospata (gilteritinib) tablets for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test (Press release, US FDA, NOV 28, 2018, View Source [SID1234531690]). The FDA also approved an expanded indication for a companion diagnostic, to include use with Xospata. The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe Technologies, Inc., is used to detect the FLT3 mutation in patients with AML.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Approximately 25 to 30 percent of patients with AML have a mutation in the FLT3 gene. These mutations are associated with a particularly aggressive form of the disease and a higher risk of relapse," said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. "Xospata targets this gene and is the first drug to be approved that can be used alone in treating patients with AML having a FLT3 mutation who have relapsed or who don’t respond to initial treatment."

AML is a rapidly progressing cancer that crowds out normal cells in the bone marrow and bloodstream, resulting in low numbers of normal blood cells and a continuous need for transfusions. The National Cancer Institute estimates that approximately 19,520 people will be diagnosed with AML this year; approximately 10,670 patients with AML will die of the disease in 2018.

The efficiency of Xospata was studied in a clinical trial of 138 patients with relapsed or refractory AML having a confirmed FLT3 mutation. Twenty-one percent of patients achieved complete remission (no evidence of disease and full recovery of blood counts) or complete remission with partial hematologic recovery (no evidence of disease and partial recovery of blood counts) with treatment. Of the 106 patients who required red blood cell or platelet transfusions at the start of treatment with Xospata, 31 percent became transfusion-free for at least 56 days.

Common side effects reported by patients in clinical trials were muscle and joint pain (myalgia/arthralgia), fatigue and elevated liver enzymes (liver transaminase). Health care providers are advised to monitor patients for posterior reversible encephalopathy syndrome (a syndrome characterized by headache, confusion, seizures and visual loss), prolonged QT interval (a heart rhythm condition that can potentially cause fast, chaotic heartbeats) and pancreatitis (inflammation in the pancreas). Rare cases of differentiation syndrome (symptoms of which may include fever, cough, trouble breathing, fluid around the lungs or heart, rapid weight gain, swelling, and renal or hepatic dysfunction) have been seen in patients taking Xospata. Women who are pregnant or breastfeeding should not take Xospata because it may cause harm to a developing fetus or newborn baby.

The FDA granted this application Fast Track and Priority Review designation. Xospata also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted the approval of Xospata to Astellas Pharma.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Advaxis to Present at LD Micro Main Event

On November 28, 2018 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported that Kenneth A. Berlin, President and Chief Executive Officer of Advaxis, will present a corporate overview at the 11th Annual LD Micro Main Event on Tuesday, December 4, 2018 at 5:00 p.m. (Pacific) (Press release, Advaxis, NOV 28, 2018, View Source [SID1234531689]). The conference will be held on December 4-6, 2018 at the Luxe Sunset Bel-Air, California.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Mr. Berlin’s presentation will be webcast live and available for replay in the Investors section of the Company’s website at www.ir.advaxis.com .

US Bioservices Selected by Bayer and Its Collaboration Partner Loxo Oncology, Inc. to Dispense Vitrakvi® (larotrectinib)

On November 28, 2018 US Bioservices, a specialty pharmacy that is a part of AmerisourceBergen, reported that it has been selected by Bayer and its collaboration partner Loxo Oncology, Inc. to dispense Vitrakvi (larotrectinib). Vitrakvi was approved by the U.S. Food and Drug Administration (FDA) on November 26, 2018 (Press release, US Bioservices, NOV 28, 2018, View Source [SID1234531686]). Vitrakvi is an oral tropomyosin receptor kinase (TRK) inhibitor for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A tumor’s underlying genomic profile is increasingly important in oncology treatment. NTRK gene fusions are genomic alterations that result in the overexpression of TRK fusion proteins. Growing research suggests that the NTRK genes can become abnormally fused to other genes, producing a TRK fusion protein that can lead to the growth and survival of solid tumors in various sites of the body. TRK fusion cancer occurs across a broad range of tumor types with varying frequency in both adult and pediatric patients. Vitrakvi is designed to inhibit overexpressed TRK fusion proteins that lead to TRK fusion cancer growth and survival.

"We’re proud to be among a very select group of pharmacies providing patients access to this important therapy," said Randy Maloziec, Vice President of BioPharma Relations at US Bioservices. "Advancements in oncology are helping many patients, and with Vitrakvi’s ability to inhibit a specific oncogenic driver irrespective of tumor location, this innovative therapy has the potential to support a diverse set of cancer patients. US Bioservices is committed to staying at the forefront of specialized support that helps patients realize the greatest benefit from new, advanced therapies."

As a specialty pharmacy, US Bioservices has more than two decades of experience supporting small patient populations and patients with various types of cancers. Through its Oncology Center of Excellence, US Bioservices’ dedicated Oncology Patient Support Team will provide customized, high-touch services that address the unique clinical profile of this therapy and specific needs of the patient population. US Bioservices’ team of pharmacists and registered nurses provide therapy-specific education and 24/7 clinical support to patients and their caregivers.

Through the breadth of resources available at AmerisourceBergen, US Bioservices develops solutions to ensure all patients on therapy receive specialized support to navigate their treatment, clinically, economically and socially. AmerisourceBergen companies supporting the launch of this therapy include ASD Healthcare for exclusive specialty distribution to hospitals, 340B eligible covered entities and any government entities; Oncology Supply for specialty distribution to physician practices; ION Solutions to support community oncology services and Lash Group for patient support services.

Vitrakvi is a limited distribution medication that is only available from select specialty pharmacies. Physicians may submit prescriptions to US Bioservices via phone (833-230-1407), fax (833-878-5917), ePrescribe or the MyPathpoint Prescriber Portal.