On December 9, 2015 Delcath Systems, Inc. (NASDAQ: DCTH), a specialty pharmaceutical and medical device company focused on oncology with an emphasis on the treatment of primary and metastatic liver cancers, reported that the results from its Phase 3 clinical study of the Delcath Hepatic Delivery System (Melphalan/HDS) for the treatment of melanoma patients with liver metastases, have been published in the December issue of the prestigious, peer-reviewed journal, Annals of Surgical Oncology (Press release, Delcath Systems, DEC 9, 2015, View Source;p=RssLanding&cat=news&id=2121277 [SID:1234508515]). The study completed enrollment in 2009 and used an earlier version of the Melphalan/HDS and procedure. Melphalan/HDS is investigational in the United States.

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!

The study, "Results of a Randomized Controlled Multi-Center Phase III Trial of Percutaneous Hepatic Perfusion (PHP) Compared to Best Available Care for patients with Melanoma Liver Metastases," by lead investigator and senior author James F. Pingpank, Jr., M.D., Associate Professor of Surgery at the University of Pittsburgh Medical Center, and first author Marybeth S. Hughes, M.D., Center for Cancer Research, National Cancer Institute, et al., compared patients randomly assigned to receive PHP treatments with melphalan using the Melphalan/HDS, or best alternative care (BAC). Patients assigned to the PHP arm were eligible to receive up to six cycles of treatment at approximately four to eight week intervals. Patients randomized to the BAC arm were permitted to cross-over into the PHP arm at radiographic documentation of hepatic disease progression; a majority of the patients in the BAC arm did, in fact, cross over to the PHP arm. Patients who received PHP were given stem cell support in the form of platelet and red blood cell infusions to mitigate toxic side effects of melphalan. The study’s primary endpoint was hepatic progression-free survival (hPFS); secondary endpoints included overall progression free survival (oPFS), overall survival (OS), hepatic objective response rate (hOR), and safety.

In the 93 patient study, results showed that patients in the PHP arm had a statistically significant longer median hPFS of 7.0 months compared to 1.6 months in the BAC control group, according to independent imaging review. Median oPFS was 5.4 months vs. 1.6 months for BAC, according to investigator assessment. Median OS for PHP was 10.6 months vs. 10 months for BAC; sub-group analysis revealed that OS among BAC patients who had crossed over to receive PHP was 13.1 months. The hOR was 36.4% for PHP vs. 2% for BAC. With the inclusion of patients with stable disease, overall hepatic disease control rates were 75% for PHP vs. 42.9% for BAC.

The most common post-procedure adverse events (AEs) were related to grade 3 and 4 bone marrow suppression, and included neutropenia (85.7%), thrombocytopenia (80%) and anemia (62.9%). Investigators attributed three deaths to treatment with PHP. An additional death resulting from a gastric perforation occurred in a patient that crossed-over to the PHP arm.

Investigators concluded that the study "demonstrated improved control of liver disease" in patients treated with Melphalan/HDS, and that the "benefit extended to oPFS", suggesting a clear clinical benefit to disease control in the liver in the patient population. Investigators noted that the earlier version of the Melphalan/HDS and PHP procedure utilized in the study was associated with significant morbidity, and recommended modifications such as the use of prophylactic bone marrow growth factors that are already required in the clinical studies that comprise Delcath’s current Clinical Development Program in the treatment of primary and metastatic liver cancers.

"Publication of the results of our prior Phase 3 trial in such a prestigious journal is a key milestone for Delcath, and underscores the importance of these data in this area of unmet medical need. In addition, it provides us with an important tool that will enhance our efforts to expand reimbursement in certain European countries," said Jennifer K. Simpson, Ph.D., MSN, CRNP, President and Chief Executive Officer of Delcath. "Since enrollment in this study was concluded in 2009, the number of treatments administered with the enhanced Melphalan/HDS product and procedure utilized commercially in Europe have exceeded the number treated during the trial. The more recent data from European experience presented at several medical congresses this fall provide us with confidence that an improved safety profile can be demonstrated in the new, pivotal global trial we expect to launch in the coming weeks."

On December 9, 2015 Halozyme Therapeutics, Inc. (NASDAQ: HALO) and Eisai Inc. reported that they will present a scientific poster entitled, "Pegylated Recombinant Human Hyaluronidase PH20 (PEGPH20) Enhances Efficacy of Eribulin Mesylate (HALAVEN) in Triple Negative Breast Cancer Xenografts" at the 38th Annual San Antonio Breast Cancer Symposium (SABCS) on Dec. 9 (Press release, Halozyme, DEC 9, 2015, View Source [SID:1234508517]).

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!

The research showed the potential impact for PEGPH20-mediated hyaluronan (HA) removal on concentrations of eribulin and antitumor effects of breast cancer therapy in preclinical models. Halozyme’s investigational new candidate drug, PEGPH20 targets the degradation of HA, a glycosaminoglycan or chain of natural sugars that may accumulate in certain tumors.

Halozyme, a biotechnology company developing novel oncology and drug-delivery therapies, and Eisai Co., Ltd., the parent company of Eisai Inc., announced a clinical collaboration in July 2015, with plans to initiate a phase 1b/2 clinical trial to evaluate PEGPH20 plus eribulin in first-line HER2-negative metastatic breast cancer patients with high-HA tumors.

"Our preclinical studies have revealed important data about the potential for PEGPH20 when used in combination of eribulin, and we are looking forward to expanding on these important preclinical findings when we initiate our clinical study with Eisai," said Dr. Helen Torley, president and CEO of Halozyme. "We remain encouraged by the potential for PEGPH20 to help patients across a range of cancer and therapy types. Our presentation today reflects the growing body of research supporting this potential of PEGPH20."

"Data presented today highlight a productive preclinical collaboration with Halozyme and support Eisai’s commitment to address the unmet medical needs of patients with advanced breast cancer," said Alton Kremer, Deputy President, Oncology PCU and Chief Medical Officer, Global Oncology Business Unit, Eisai Inc. "We are encouraged by these preclinical data and look forward to enrolling patients in the clinical trial early next year."

SABCS Poster Presentation Details:

Poster Session:
P1-03-09, Wednesday, Dec. 9, 5:00 p.m. CT

About Eribulin Mesylate Injection (Available as HALAVEN in the United States)
The above publication does not necessarily contain information that is consistent with the U.S. prescribing information for HALAVEN (eribulin mesylate). It is an investigational use and there is no guarantee that this use will become available commercially.

HALAVEN (eribulin mesylate) injection is indicated for patients with metastatic breast cancer who have received at least two chemotherapeutic regimens for the treatment of metastatic breast cancer. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. Eribulin is a synthetic analog of halichondrin B, a natural product that was isolated from the marine sponge Halichondria okadai. First in the halichondrin class, eribulin is a microtubule dynamics inhibitor with a distinct binding profile. Based on in vitro studies, eribulin exerts its effect via a tubulin-based antimitotic mechanism ultimately leading to apoptotic cell death after prolonged and irreversible mitotic blockage.

Important Safety Information
Neutropenia

Monitor complete blood counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting longer than 7 days

Severe neutropenia (ANC <500/mm3) lasting more than 1 week occurred in 12% (62/503) of patients. Patients with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels

Grade 3 and Grade 4 neutropenia occurred in 28% and 29%, respectively, of patients who received eribulin. Febrile neutropenia occurred in 5% of patients and two patients (0.4%) died from complications

Peripheral Neuropathy

Patients should be monitored closely for signs of peripheral motor and sensory neuropathy
Grade 3 peripheral neuropathy occurred in 8% of patients, and Grade 4 in 0.4% of patients who received eribulin. Delay administration of eribulin until resolution to Grade 2 or less
Neuropathy lasting more than 1 year occurred in 5% of patients. Twenty-two percent of patients developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days)
Peripheral neuropathy (5%) was the most common adverse reaction resulting in discontinuation

Pregnancy Category D

Eribulin is expected to cause fetal harm when administered to a pregnant woman and patients should be advised of these risks
QT Prolongation

In an uncontrolled ECG study in 26 patients, QT prolongation was observed on Day 8, independent of eribulin concentration, with no prolongation on Day 1. ECG monitoring is recommended for patients with congestive heart failure; bradyarrhythmias; concomitant use of drugs that prolong QT interval, including Class Ia and III antiarrhythmics; and electrolyte abnormalities
Correct hypokalemia or hypomagnesemia prior to initiating eribulin and monitor electrolytes periodically during therapy. Avoid in patients with congenital long QT syndrome

Hepatic and Renal Impairment

For patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic and/or moderate or severe (CrCl 15-49 mL/min) renal impairment, a reduction in starting dose is recommended

Most Common Adverse Reactions

Most common adverse reactions (>25%) reported in patients receiving eribulin were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%)
The most common serious adverse reactions reported in patients receiving eribulin were febrile neutropenia (4%) and neutropenia (2%)

For more information about HALAVEN, click here for the full Prescribing Information.

On December 9, 2015 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported it will highlight three scientific presentations related to its myRisk Hereditary Cancer test at the 2015 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas (Press release, Myriad Genetics, DEC 9, 2015, View Source [SID:1234508518]). Data include results from studies that advance the understanding of hereditary cancer testing using multi-gene panels to evaluate patients at risk for or diagnosed with breast cancer.

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!

"Our collaborators will present data at SABCS this year that show multi-gene panel testing with myRisk Hereditary Cancer provides clinically significant results that drive appropriate changes in patient care," said Johnathan Lancaster, M.D., Ph.D., chief medical officer, Myriad Genetic Laboratories. "Importantly, there are new data that demonstrate the positive perceptions from patients after they receive a multi-gene test result. Furthermore, as we expand our testing to broader gene panels and share scientific outcomes from our research collaborations, important new questions are being asked that will expand our thinking about exactly which patients should be tested for hereditary cancer."

Details about the featured myRisk Hereditary Cancer presentations at SABCS are below. Follow Myriad on Twitter via @MyriadGenetics and stay informed about symposium news and updates by using the hashtag #SABCS15.

myRisk Hereditary Cancer Poster Presentations

Title: Interim analysis of multiplex gene panel testing for inherited susceptibility to breast cancer.
Date: Friday, Dec. 11, 2015: 5:00 to 7:00 p.m. CT.
Location: Poster Discussion PD7-01.
Presenter: Dr. Gregory Idos, Stanford University Cancer Institute.

This multi-center prospective study was designed to analyze data from 2,000 patients undergoing cancer-risk assessment using the myRisk Hereditary Cancer 25-gene panel test. The objective was to determine the benefits of multi-gene panel testing versus traditional genetic testing. The interim analysis of the first 332 patients tested found that 11 percent were positive for a deleterious mutation. Among participants testing negative for BRCA1 and BRCA2 mutations, the myRisk test identified deleterious mutations in 14 patients, representing a 61 percent increase over BRCA testing alone and prompting clinically appropriate risk reduction recommendations and enhanced cancer surveillance. These findings demonstrate the ability of the myRisk Hereditary Cancer test to identify a subset of patients with deleterious mutations who historically would have been missed by traditional genetic testing for BRCA1/2 alone, and who could receive appropriate medical management as a result.

Title: The patient experience in a prospective trial of multiple-gene panel testing for cancer risk.
Date: Thursday, Dec.10, 2015: 7:30 to 9:00 a.m. CT.
Location: Poster P2-09-07.
Presenter: Dr. Allison Kurian, Stanford University Cancer Institute

In this study, 2,000 diverse patients at risk for hereditary breast/ovarian cancer syndrome were evaluated to determine the patient experience following genetic testing with the myRisk Hereditary Cancer test. Patients were surveyed at entry and three months after testing using the Multidimensional Impact of Cancer Risk Assessment (MICRA) scale. An interim analysis of the first 332 patients found that 87 percent said they did not regret learning about the results and 81 percent wanted all their genetic test results for all 25 genes tested. Although the study is ongoing, these interim results suggest there is no evidence of an increase in cancer- or testing-related distress/uncertainty after patients received their test results.

Title: Predisposing germline mutations in an unselected academic breast cancer (BC) cohort.
Date: Wednesday, Dec. 9, 2015: 5:00 to 7:00 p.m. CT.
Location: Poster P1-08-07.
Presenter: Dr. Judy Garber, Dana-Farber Cancer Institute

In this study, 456 patients newly diagnosed with breast cancer were evaluated for mutations in 25 cancer genes using the myRisk Hereditary Cancer test. The results show that 11 percent of the patients in a single academic institution had a germline mutation in a breast cancer predisposition gene. Approximately 7 percent were in BRCA1/2 genes and 4 percent were in other cancer genes. Of the 49 women with deleterious mutations associated with breast cancer, 21 (43 percent) were diagnosed after age 45. This finding suggests that patients diagnosed with breast cancer at older ages may benefit from genetic testing with the myRisk Hereditary Cancer gene panel test.

For more information about these presentations, please visit the SABCS website at View Source

About Myriad myRisk Hereditary Cancer Testing

The Myriad myRisk Hereditary Cancer test uses next-generation sequencing technology to evaluate 25 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma. For more information visit: View Source

On December 9, 2015 Neon Therapeutics, an immuno-oncology company developing neoantigen-based therapeutic vaccines and T cell therapies to treat cancer, reported that the company has entered into a license agreement with the Broad Institute, Dana-Farber Cancer Institute and Massachusetts General Hospital for technology to be utilized in Neon Therapeutics’ pipeline (Press release, Neon Therapeutics, DEC 9, 2015, View Source [SID1234517520]).

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!

The work of Neon Therapeutics co-founders Catherine J. Wu, M.D., at the Broad Institute and Dana-Farber Cancer Institute, Nir Hacohen, Ph.D., at the Broad Institute and Massachusetts General Hospital, and Ed Fritsch, Ph.D., at the Broad Institute and Dana-Farber Cancer Institute, led to the development of a personalized neoantigen vaccine, which is the foundation for Neon Therapeutics’ proprietary lead compound, NEO-PV-01. The project was originated and led by the Broad Institute and was philanthropically funded in part by the Blavatnik Family Foundation. Dana-Farber Cancer Institute is currently enrolling two investigator-initiated trials with additional trials planned. Neon Therapeutics will build upon this research and initiate a company-sponsored clinical trial in 2016.

"Neon Therapeutics’ approach was borne out of years of research focused on developing novel cancer immunotherapies based on unique mutations present in the tumor DNA of each patient," said Cary Pfeffer, M.D., interim chief executive officer of Neon Therapeutics. "We are privileged to license technology from The Broad Institute, Dana-Farber Cancer Institute and Massachusetts General Hospital, each a world-leading cancer research institution, to leverage this excellent science to develop innovative neoantigen-based therapies."

On December 8, 2015 FUJIFILM Corporation (President: Shigehiro Nakajima) reported the progress in a Phase I clinical trial of anti-cancer agent FF-10501 in the United States in patients with relapsed or refractory myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) (Press release, Fujifilm, DEC 8, 2015, View Source [SID:1234508497]). The emerging results have revealed that to date FF-10501 was well tolerated in those patients and produced partial remission*1 and marrow complete remission*2 in some patients.

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!

These results were presented on December 7th at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting (Orland, Florida), the biggest hematology meeting in the world, by principal investigator, Professor Garcia-Manero MD, of The University of Texas MD Anderson Cancer Center*3 (MD Anderson Cancer Center hereafter).

MDS is a type of hematological malignancy, in which the disorder of blood-forming hematopoietic stem cells (myelodysplasia) causes inefficient production of blood cells triggering cytopenia. Current MDS patients in the United States and in Japan are estimated to be around 60,000 and 11,000, respectively, many of them in the senior age group. It is also a refractory disease progressing to AML for some patients with poor prognosis. AML is characterized by a higher rate of abnormal hematopoietic stem cells in bone marrow than in MDS, and inefficient production of blood cells and peripheral organ failure due to migrating myeloblasts. The numbers of patients with AML in the United States and in Japan are estimated to be around 25,000 and 6,000, respectively.

Fujifilm initiated the Phase I clinical trial of FF-10501 in patients with blood cancer at MD Anderson Cancer Center in the United States in August 2014. Although the trial is still underway, some positive responses have been observed in the study as follows:

– FF-10501 was well tolerated in all 17 patients〔AML (13), MDS (4)〕
– FF-10501 produced stable disease in 6 AML and 2 MDS patients
– FF-10501 produced 2 partial remissions in AML patients and 1 marrow complete remission in MDS patients

Fujifilm will continue the study to further evaluate tolerability and efficacies with higher doses at MD Anderson Cancer Center and proceed to early Phase IIa study.

Fujifilm tapped into the advanced technology to synthesize and design chemical compounds, nurtured through the development of photographic films, to develop FF-10501. The technology utilized in the development for enhancing its temporal stability and applying strong analysis technology to elucidate new mechanisms of action and identify biomarker candidates for verifying its efficacy. The agent is expected not only to inhibit the growth of hematological cancer cells but also promote their differentiation to cells with normal functions.

Fujifilm is dedicated to research and development for innovative pharmaceutical products and new production processes by combining the technologies and know-how accumulated in the photographic film business including chemical synthesis capacity, design ability, analysis technology, nanotechnology, and production technology, with the technological expertise of its pharmaceutical affiliates such as Toyama Chemical. Defining "oncology", a field with numerous unmet medical needs, as its focal area, the company will actively promote research and development to expand business deployment and supply innovative pharmaceutical products so as to contribute to resolving social issues.