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FDA Approves IMLYGIC™ (Talimogene Laherparepvec) As First Oncolytic Viral Therapy In The US

On October 27, 2015 Amgen (NASDAQ: AMGN) reported that the U.S. Food and Drug Administration (FDA) has approved the Biologics License Application for IMLYGIC (talimogene laherparepvec), a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous and nodal lesions in patients with melanoma recurrent after initial surgery (Press release, Amgen, OCT 27, 2015, View Source [SID:1234507812]). IMLYGIC has not been shown to improve overall survival or have an effect on visceral metastases. IMLYGIC is the first oncolytic viral therapy approved by the FDA based on therapeutic benefit demonstrated in a pivotal study.1-3

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IMLYGIC is a genetically modified herpes simplex virus type 1 designed to replicate within tumors and produce an immunostimulatory protein called granulocyte-macrophage colony-stimulating factor (GM-CSF). IMLYGIC causes cell lysis, or death, which ruptures tumors, releasing tumor-derived antigens, which along with GM-CSF, may promote an anti-tumor immune response. However, the exact mechanism of action is unknown.

"IMLYGIC is the first clinical and regulatory validation of an oncolytic virus as a therapy, which Amgen is proud to bring to patients with a serious form of skin cancer. Not all melanoma patients currently benefit from available therapies, and IMLYGIC represents an important new option that can provide meaningful durable responses for patients with this aggressive and complex disease," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Immunotherapy is an exciting area for cancer research, and we are currently studying IMLYGIC in combination with other immunotherapies in advanced melanoma and other solid tumors."

"Advanced melanoma remains a complex disease to treat, requiring the use of several modalities over the course of a patient’s therapeutic journey," said Howard L. Kaufman, M.D., the principal investigator for the pivotal trial (OPTiM), associate director for Clinical Science at the Rutgers Cancer Institute of New Jersey and president of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). "As an oncolytic viral therapy, IMLYGIC has a unique approach, and provides another option for treating eligible patients with unresectable disease that has recurred after initial surgery."

Metastatic melanoma continues to be one of the most difficult-to-treat cancers because it is often insensitive to chemotherapy, can be highly aggressive and can require several different types of treatment depending on the stage and location of the disease and health of the patient.4,5 Despite new therapeutic options, additional treatments are needed – particularly for patients with metastatic disease.

Amgen intends to make IMLYGIC available to patients in the U.S. within a week. Amgen anticipates the average cost of IMLYGIC therapy to be approximately $65,000. Given that IMLYGIC represents a novel and first-in-class oncolytic viral therapy, Amgen expects variability of IMLYGIC dosing from patient to patient. Therefore, Amgen intends to work with the healthcare community to implement a program that helps limit the average cost of IMLYGIC therapy to $65,000 for eligible participating institutions.

Amgen is committed to helping clinically appropriate patients access our medicines and will provide assistance for IMLYGIC in the U.S. in the following ways:

Free medicines through The Safety Net Foundation are available to qualifying individuals with no or limited drug coverage.
Co-pay coupon program for IMLYGIC through the Amgen FIRST STEP Program to help commercially insured patients meet their co-payment obligations; this program has no income requirement. Further information about eligibility requirements can be found at www.amgenfirststep.com.
Information about independent co-pay assistance foundations that give grants to qualifying patients who have difficulty paying out-of-pocket costs for medicines manufactured from across all of the industry.

For more information, visit www.amgenassistonline.com.

About the OPTiM Study
The approval of IMLYGIC is based on data from Study 005/05, referred to as OPTiM. OPTiM was a Phase 3, multicenter, open-label, randomized clinical trial comparing IMLYGIC to GM-CSF in patients with advanced melanoma (Stage IIIB, IIIC, or IV) that was not surgically resectable. The primary endpoint of the study was durable response rate (DRR), defined as the percent of patients with complete response (CR) or partial response (PR) maintained continuously for a minimum of six months.

OPTiM enrolled 436 patients. In the study, 16.3 percent of patients treated with IMLYGIC achieved a durable response compared to 2.1 percent of patients treated with GM-CSF (p <0.0001). Of the patients who experienced a durable response, 29.1 percent had a durable CR and 70.8 percent had a durable PR. In the study, the median time to response was 4.1 (range: 1.2 to 16.7) months in the IMLYGIC arm.

The most common adverse drug reactions in IMLYGIC treated patients were fatigue, chills, pyrexia, nausea, influenza-like illness and injection site pain. Most adverse reactions reported were mild or moderate in severity and generally resolved within 72 hours. The most common grade 3 or higher adverse reaction was cellulitis.2

About IMLYGIC (talimogene laherparepvec)
IMLYGIC is a genetically modified herpes simplex virus type 1 injected directly into tumors where it replicates inside tumors and produces GM-CSF, an immunostimulatory protein. IMLYGIC then causes the tumor to rupture and die in a process called lysis. The rupture of the tumor causes the release of tumor-derived antigens, which together with virally-derived GM-CSF may promote an anti-tumor immune response. However, the exact mechanism of action is unknown and being further investigated.

Merrimack and Baxalta Announce Enrollment of First Patient in Phase 2 Study of ONIVYDE™ (irinotecan liposome injection) in Previously Untreated Front-line Metastatic Pancreatic Cancer

On October 27, 2015 Merrimack (Nasdaq: MACK) and Baxalta Incorporated (NYSE: BXLT) reported the enrollment of the first patient in an exploratory Phase 2 clinical study of ONIVYDE (irinotecan liposome injection), also known as MM-398 or "nal-IRI," in previously untreated, metastatic pancreatic adenocarcinoma (Press release, Merrimack, OCT 27, 2015, View Source [SID:1234507804]).

The Phase 2 clinical study of ONIVYDE in patients with previously untreated, metastatic pancreatic adenocarcinoma will assess the safety and efficacy of the combination of ONIVYDE plus fluorouracil (5-FU) and leucovorin (LV), with or without the addition of oxaliplatin, versus nab-paclitaxel and gemcitabine. The start-up of this study resulted in $62.5M of milestone payments to Merrimack from Baxalta.

"The initiation of this Phase 2 study is an important step in evaluating ONIVYDE’s effectiveness as a front-line treatment option for patients diagnosed with metastatic pancreatic cancer. This design allows us to quickly and efficiently learn about the safety and efficacy of these potential new regimens prior to entering into a large, confirmatory Phase 3 study," said Eliel Bayever, M.D., Vice President at Merrimack and medical director for ONIVYDE.

"Our team is extremely excited to be the first center in the world to open this trial of ONIVYDE in front-line metastatic pancreatic cancer given the results of the NAPOLI trial in the post-gemcitabine setting," said Dr. Andrew Dean, one of the principal investigators on the study and an Oncologist at St John of God Hospital Subiaco in Australia.

In addition to pancreatic cancer, there are ongoing Phase 1 studies of ONIVYDE in glioma, breast cancer, gastric cancer and pediatric solid tumors.

"This trial is part of our broad development plan for ONIVYDE in solid tumors that have high unmet medical need," said John Orloff, M.D., head of Research & Development and chief scientific officer, Baxalta. "By expanding our research of ONIVYDE into patients who have not been previously treated for metastatic pancreatic cancer, our hope is that we learn more about its potential to meet the needs of people who currently have few approved treatment options."

Merrimack and Baxalta have entered into an exclusive licensing agreement to develop and commercialize ONIVYDE outside of the United States.A Marketing Authorization Application is under review in the European Union for the treatment of adult patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy. PharmaEngine, Inc. (Taipei, Taiwan) holds the rights to commercialize ONIVYDE in Taiwan.

Clinical Study of ONIVYDE in Previously Untreated, Metastatic Pancreatic Adenocarcinoma

The study will be conducted in two parts, first assessing the safety of ONIVYDE in combination with 5-FU/LV and oxaliplatin, and then expanding into a three arm randomized study assessing the safety and efficacy of the combination of ONIVYDE and 5-FU/LV with or without oxaliplatin versus nab-paclitaxel and gemcitabine. Eligible patients for the study must have received no prior systemic treatment.

In the first part of the study, approximately 6-18 patients will be enrolled. The primary outcome for Part 1 of the study is to evaluate the safety and tolerability of ONIVYDE in combination with 5-FU/LV and oxaliplatin. In the second part of the study, an additional 150 patients (50 patients per arm) with previously untreated, metastatic pancreatic adenocarcinoma will be enrolled and randomized to receive either ONIVYDE in combination with 5-FU/LV and oxaliplatin, ONIVYDE in combination with 5-FU/LV, or nab-paclitaxel and gemcitabine. In Part 2, efficacy of the ONIVYDE containing regimens will be compared to the nab-paclitaxel and gemcitabine regimen, evaluating progression free survival (PFS) rate at 24 weeks, as well as overall survival, PFS, objective response rate, tumor marker CA19-9 response, safety and tolerability.

Merrimack and Baxalta plan to conduct the study at sites in the United States, Canada, Europe, Australia, New Zealand, Taiwan and South Korea. The first patient in the study was dosed at St. John of God Subiaco Hospital in Subiaco, Western Australia. For more information, please visit www.clinicaltrials.gov (Identifier: NCT02551991). Based on the current design of this study, data are expected in the first half of 2017. Guidance will be updated as recruitment continues.

About Pancreatic Cancer

Pancreatic cancer is rare and deadly. It accounts for only 3% of all cancer cases1, but is the fourth leading cause of cancer-related death2, leading to a five year survival rate of only 7%3. Each year an estimated 49,000 new cases are diagnosed in the United States3, two-thirds of which are among people aged 65 or older4. There are an estimated 338,000 new cases diagnosed each year worldwide5.

The pancreas is composed of two main cell types: exocrine and endocrine. Exocrine tumors are the most common type of pancreatic cancer, accounting for 96% of all cases3. Adenocarcinoma, a sub-type of exocrine tumors, comprises of 95% of all exocrine tumors1.

Because the signs and symptoms of pancreatic cancer are non-specific and may not appear until the disease has spread to other sites, approximately 80% of patients are not candidates for surgery2, instead receiving chemotherapy as the mainstay of their therapy. The majority of these patients receive gemcitabine-based therapy during either adjuvant/neoadjuvant treatment or during first- or second-line therapy for metastatic disease 6.

About ONIVYDE [pronounced \ ‘on – ih – vide \]

ONIVYDE (irinotecan liposome injection), also known as MM-398 or "nal-IRI," is a novel encapsulation of irinotecan in a liposomal formulation. The activated form of irinotecan is SN-38, which functions by inhibiting topoisomerase I (an essential enzyme involved in DNA transcription and replication) and promoting cell death. ONIVYDE was recently approved by the U.S. Food and Drug Administration in combination with fluorouracil and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. For full prescribing information, including Boxed WARNING, please visit www.ONIVYDE.com.

Celator® Pharmaceuticals Announces VYXEOS™ (CPX-351) Selected As Best Nanomedicine Product

On October 27, 2015 Celator Pharmaceuticals, Inc. (Nasdaq: CPXX) reported that VYXEOS (formerly referred to as CPX-351) was recognized with the Nanomedicine Award 2015 (Press release, Celator Pharmaceuticals, OCT 27, 2015, View Source [SID:1234507799]). This award recognizes projects or products that have been developed using innovative solutions based on nanotechnology.

The Nanomedicine Award 2015 honors the best international nanomedicine innovations in two categories; (1) Best Nanomedicine Early Clinical Stage Project Award, and (2) Best Nanomedicine Product or Deal Award.

VYXEOS was selected in the category of the Best Nanomedicine Product or Deal Award. The international program is organized by the European Technology Platform for Nanomedicine (ETPN) together with the consortium Enabling Nanomedicine Translation (ENATRANS). A panel of pharmaceutical industry specialists with global experience in research and development, as well as commercial roles, reviewed the applications and selected VYXEOS.

Dr. Lawrence Mayer, President and Chief Scientific Officer of Celator will accept the award on behalf of the company at BIO-Europe 2015 in Munich, Germany on November 3, 2015. Dr. Mayer was also invited to give a presentation on VYXEOS at the award ceremony.

"We are honored to receive this award as recognition of the impact VYXEOS has made to date, and the potential to become the first product to significantly improve survival of AML patients in over 40 years," said Dr. Mayer. "VYXEOS represents a validation of the CombiPlex approach which uses nano-scale carriers to coordinate the delivery of synergistic drug ratios to cancer cells. We are applying our nanotechnology-based approaches to traditional cytotoxics as well as an array of molecularly targeted agents with the hope of increasing their therapeutic benefit and changing the paradigm of combination therapy for cancer."

The objective of the Nanomedicine Award 2015 is to recognize innovative product developments in nanomedicine and to promote these advances, and the field of nanotechnology, within the international biotechnology and pharmaceutical community. To be selected products must:

Address unmet medical needs
Not be feasible without nanotechnology
Be distinct from the "standard approaches" such as new chemical entities/small molecules and biologics
Have a clearly defined market

About VYXEOS (CPX-351)

Celator’s Phase 3 study comparing VYXEOS to the current standard of care, known as 7+3, is being conducted in patients with high-risk (secondary) AML. The Phase 3 study completed enrollment in November 2014. Initial data, from a secondary endpoint, showed an improvement in induction response rate in favor of VYXEOS over the 7+3 control arm: 47.7% versus 33.3% respectively, for a 43.2% relative improvement. The study’s primary endpoint, overall survival, is expected to be reported in the first quarter of 2016 along with important safety information.

Advaxis Launches MINE(TM) Collaboration

On October 27, 2015 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported the launch of a research collaboration with Memorial Sloan Kettering Cancer Center (MSK), a premier cancer center committed to patient care and innovative research, to evaluate the immunologic and anti-tumor activity of patient tumor-specific, neoepitope-based immunotherapy (Press release, Advaxis, OCT 27, 2015, View Source [SID:1234507798]).

The goal of the collaboration, titled "MINE" (My Immunotherapy Neo-Epitopes), is to use Advaxis’s Lm Technology to develop neo-epitope immunotherapies based on an individual patient’s tumor ("ADXS-NEO"). MINE will first focus on a preclinical study of Advaxis’s new construct approach to evaluate the immunologic effects and anti-tumor activity of a personalized immunotherapy in a mouse tumor model. Advaxis will use learnings from the MINE collaboration to identify and target neoepitopes using Lm Technology and later develop patient specific immunotherapy constructs that incorporate the neoepitope sequences identified in the patient’s tumor cells. Clinical studies using ADXS-NEO, to be conducted at MSK, are in development.

"Existing immunotherapies have been shown to very effectively augment tumor immunity in a subset of patients, leading to durable responses," said Jedd D. Wolchok, M.D., Ph.D., Chief of Melanoma and Immunotherapeutics Service, Department of Medicine and Ludwig Center at MSK. "However, recent advances in genome sequencing have made it possible to investigate the role of neoepitopes, or unique mutations, in an individual patient’s cancer, which may allow for the development of specific immunotherapies that generate and enhance an immune response directed against the neoepitopes contained in a patient’s tumor."

Advaxis’s Lm Technology is uniquely positioned to take advantage of the advances in genome sequencing which occurred in recent years. Lm Technology has the bandwidth to potentially target all of a patient’s immunogenic cancer neoepitopes, eliminating the need to use "predictive algorithms." This technology can enable the development of truly individualized immunotherapies that can be manufactured in a cost-effective and timely manner.

"We welcome this collaboration with MSK, a top cancer institution, which will allow us to study our clinically validated Lm Technology in a new way to deliver precision medicine by personalizing neoepitopes specific to a patient’s tumor," said David J. Mauro, M.D., Ph.D., Executive Vice President and Chief Medical Officer of Advax

Kite Pharma and Alpine Immune Sciences Announce Research Collaboration and License Agreement to Enhance Immune Response in the Tumor Microenvironment

On October 27, 2015 Kite Pharma, Inc. (Kite) (Nasdaq:KITE) reported that it has entered into a worldwide research and license agreement with Alpine Immune Sciences, Inc. (AIS), a privately-held biotechnology company, to discover and develop protein-based immunotherapies targeting the immune synapse to treat cancer (Press release, Kite Pharma, OCT 27, 2015, View Source [SID:1234507797]). AIS will grant Kite an exclusive license to two programs from its transmembrane immunomodulatory protein (TIP) technology, which Kite plans to further engineer into chimeric antigen receptor (CAR) and T cell receptor (TCR) product candidates. This collaboration will accelerate Kite’s efforts to establish the next generation of engineered T cell therapies specifically designed to overcome the inhibitory mechanisms present in the tumor microenvironment.

"The field of immuno-oncology has the potential to significantly improve the outcome of patients with cancer," said Arie Belldegrun, M.D., FACS, Chairman, President and Chief Executive Officer of Kite. "We believe the ability of AIS’ TIP technology to modulate the immune synapse can be incorporated into engineered T cell therapies to advance CAR and TCR product candidates into multiple tumor types. This collaboration is another example of Kite’s continuing commitment to advancing our pipeline through transformative technologies grounded in innovative science."

Under the terms of the collaboration, Kite will make an upfront payment to AIS of $5 million and additional payments to support AIS’ research. AIS will be eligible to receive milestone payments based upon the successful achievement of pre-specified research, clinical, and regulatory milestones totaling $530 million plus low single-digit royalty payments on product sales. Kite will receive an exclusive, worldwide license to research, develop and commercialize engineered autologous T cell therapies incorporating two programs coming from the AIS platform.

"AIS was established with a team of experienced scientists to capitalize on our keen understanding of immunology and protein engineering," said Mitchell H. Gold, M.D., Executive Chairman. "At AIS, we have a robust discovery platform to identify molecules capable of directly modulating the immune synapse. We look forward to working with Kite, a company that uniquely understands the complexities surrounding cancer biology."