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Janssen Announces the Initiation of Two Studies Evaluating Daratumumab (DARZALEX®) and Atezolizumab in Multiple Myeloma and Solid Tumor

On March 21, 2016 Janssen Research & Development, LLC reported it has entered into a clinical trial collaboration agreement with Genentech, a member of the Roche Group, to initiate two studies to determine the safety and tolerability of daratumumab (DARZALEX), the first CD38-directed monoclonal antibody (mAb), in combination with atezolizumab, an investigational mAb designed to bind with a protein called programmed cell death-ligand 1 (PD-L1) (Press release, Johnson & Johnson, MAR 21, 2016, View Source [SID:1234509812]). These studies will assess the potential of the combination therapy in multiple myeloma and in solid tumor. Atezolizumab is currently in development by Roche. Janssen licensed daratumumab from Genmab A/S and is responsible for development and marketing.

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As part of the collaboration, Janssen will sponsor a Phase 1b, open-label, multicenter study that will investigate the potential of daratumumab in combination with atezolizumab in patients with solid tumor. Genentech is the sponsor of an ongoing Phase 1b, open-label, multicenter study that will be amended to assess atezolizumab in combination with daratumumab, with daratumumab and lenalidomide, and with daratumumab and pomalidomide in patients with relapsed or refractory multiple myeloma. These studies are anticipated to start dosing patients within a year.

"We are excited to see if the immunomodulatory properties of daratumumab may have synergistic treatment effects when used in combination with this promising anti-PDL1 antibody," said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen Research & Development. "This is the first time we’re exploring daratumumab in solid tumor, and we look forward to better understanding how combining these two immunotherapies may potentially benefit patients with multiple myeloma and solid tumor, who are urgently in need of new options."

In November 2015, DARZALEX was approved by the U.S. Food and Drug Administration for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous use is the first CD38-directed monoclonal antibody (mAb) approved anywhere in the world.1 CD38 is a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.2 Daratumumab is believed to induce tumor cell death through apoptosis, in which a series of molecular steps in a cell lead to its death1,3 as well as immunomodulatory effects and multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).1,4,5 Five Phase 3 clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin’s lymphoma. DARZALEX is the first mAb to receive regulatory approval to treat relapsed or refractory multiple myeloma.1

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize DARZALEX. DARZALEX is commercialized in the U.S. by Janssen Biotech, Inc.6

DARZALEX (daratumumab) Important Safety Information – Professional
CONTRAINDICATIONS – None

WARNINGS AND PRECAUTIONS
Infusion Reactions – DARZALEX can cause severe infusion reactions. Approximately half of all patients experienced a reaction, most during the first infusion. Infusion reactions can also occur with subsequent infusions. Nearly all reactions occurred during infusion or within 4 hours of completing an infusion. Prior to the introduction of post-infusion medication in clinical trials, infusion reactions occurred up to 48 hours after infusion. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, and hypertension. Signs and symptoms may include respiratory symptoms, such as cough, wheezing, larynx and throat tightness and irritation, laryngeal edema, pulmonary edema, nasal congestion, and allergic rhinitis. Less common symptoms were hypotension, headache, rash, urticaria, pruritus, nausea, vomiting, and chills.

Pre-medicate patients with antihistamines, antipyretics and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt infusion for reactions of any severity and institute medical management as needed. Permanently discontinue therapy for life-threatening (Grade 4) reactions. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients the first and second day after all infusions. Patients with a history of obstructive pulmonary disorders may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with obstructive pulmonary disorders.

Interference with Serological Testing – Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Interference with Determination of Complete Response – Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both, the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Adverse Reactions – The most frequently reported adverse reactions (incidence =20%) were: fatigue, nausea, back pain, pyrexia, cough, and upper respiratory tract infection.

Serious adverse reactions were reported in 51 (33%) patients. The most frequent serious adverse reactions were pneumonia (6%), general physical health deterioration (3%), and pyrexia (3%).

DRUG INTERACTIONS – No drug interaction studies have been performed.

Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure induce strong immune responses and display therapeutic effects both in murine TC-1 and TRAMP-C2 tumors when combined with docetaxel chemotherapy.

High hydrostatic pressure (HHP) has been shown to induce immunogenic cell death of cancer cells, facilitating their uptake by dendritic cells (DC) and subsequent presentation of tumor antigens. In the present study, we demonstrated immunogenicity of the HHP-treated tumor cells in mice. HHP was able to induce immunogenic cell death of both TC-1 and TRAMP-C2 tumor cells, representing murine models for human papilloma virus-associated tumors and prostate cancer, respectively. HHP-treated cells induced stronger immune responses in mice immunized with these tumor cells, documented by higher spleen cell cytotoxicity and increased IFNγ production as compared to irradiated tumor cells, accompanied by suppression of tumor growth in vivo in the case of TC-1 tumors, but not TRAMP-C2 tumors. Furthermore, HHP-treated cells were used for DC-based vaccine antigen pulsing. DC co-cultured with HHP-treated tumor cells and matured by a TLR 9 agonist exhibited higher cell surface expression of maturation markers and production of IL-12 and other cytokines, as compared to the DC pulsed with irradiated tumor cells. Immunization with DC cell-based vaccines pulsed with HHP-treated tumor cells induced high immune responses, detected by increased spleen cell cytotoxicity and elevated IFNγ production. The DC-based vaccine pulsed with HHP-treated tumor cells combined with docetaxel chemotherapy significantly inhibited growth of both TC-1 and TRAMP-C2 tumors. Our results indicate that DC-based vaccines pulsed with HHP-inactivated tumor cells can be a suitable tool for chemoimmunotherapy, particularly with regard to the findings that poorly immunogenic TRAMP-C2 tumors were susceptible to this treatment modality.

NanoString Technologies Receives Favorable Final Local Coverage Determination by Noridian Healthcare Solutions for Its Prosigna Breast Cancer Assay

On March 21, 2016 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported that Noridian Healthcare Solutions, LLC, a Medicare Administrative Contractor (MAC) for two Medicare jurisdictions covering 13 states, has issued favorable final local coverage determinations (LCDs) for the Prosigna Breast Cancer Assay, effective for services provided on or after May 3, 2016 (Press release, NanoString Technologies, MAR 21, 2016, View Source [SID:1234509770]).

"The favorable LCDs published by Noridian represent an important step forward in ensuring patients have access to Prosigna," said Brad Gray, President and Chief Executive Officer of NanoString Technologies. "When the Noridian LCD becomes effective, Medicare will cover Prosigna for breast cancer patients in 39 states, in line with the assumptions underlying our expectations for Prosigna this year. Our reimbursement team is working aggressively to further expand coverage to reach as many patients as possible."

The final LCDs, which are consistent with the draft guidance issued by Noridian on October 1, 2015, confirm the coverage policy for Medicare beneficiaries, and include reimbursement coverage for postmenopausal patients with ER+, lymph node-negative, stage I or II breast cancer; and ER+, lymph node-positive (1-3 positive nodes), stage II breast cancer. The LCDs are posted to the Medicare Coverage Database on the Centers for Medicare & Medicaid Services (CMS) website at: View Source;ContrId=364 and View Source;ContrId=345.

The final LCDs apply to the JE jurisdiction, comprising California, Nevada, Hawaii, Guam, American Samoa and Northern Mariana Islands, and the JF jurisdiction, comprising Washington, Oregon, Idaho, Montana, Wyoming, North Dakota, South Dakota, Utah, Arizona and Alaska.

About the Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Dx Analysis System

The Prosigna Assay provides a risk category and numerical score for assessment of the risk of distant recurrence of disease at 10 years in postmenopausal women with node-negative (Stage I or II) or node-positive (Stage II), hormone receptor-positive (HR+) breast cancer. Based on the PAM50 gene signature initially discovered by Charles Perou, Ph.D. and colleagues, the Prosigna Assay is an in vitro diagnostic tool that utilizes gene expression data weighted together with clinical variables to generate a risk category and numerical score to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay measures gene expression levels of RNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor tissue previously diagnosed as invasive breast carcinoma.

The Prosigna Assay requires minimal hands-on time and runs on NanoString’s proprietary nCounter Dx Analysis System, which offers a reproducible and cost-effective way to profile many genes simultaneously with high sensitivity and precision.

The nCounter Dx Analysis System is a highly automated and easy-to-use platform that utilizes a novel digital barcoding chemistry to deliver high precision multiplexed assays. The system is available in the multi-mode FLEX configuration, which is designed to meet the needs of high-complexity clinical laboratories seeking a single platform with the flexibility to run the Prosigna Breast Cancer Assay and, when operated in the "Life Sciences" mode, process translational research experiments and multiplexed assays developed by the laboratory.

In the United States, the Prosigna Assay is available for diagnostic use when ordered by a physician. The Prosigna Assay has been CE-marked and is available for use by healthcare professionals in the European Union and other countries that recognize the CE Mark, as well as Canada, Israel, Australia, New Zealand and Hong Kong.

In the U.S., the Prosigna Assay is indicated in female breast cancer patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care, either as:

(1) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors or (2) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 nodes), Stage II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors. The device is not intended for patients with four or more positive nodes.

For more information, please visit www.prosigna.com.

Myriad Genetics Teams Up with Access Health® to Educate the Public about Hereditary Cancer and Genetic Testing

On March 21, 2016 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, and Access Health, an educational program focused on health and wellness, reported that they will air an educational program on hereditary cancer that will appear on Lifetime (Press release, Myriad Genetics, MAR 21, 2016, View Source [SID:1234509769]). The program, titled "Hereditary Cancer Risk Assessment and Testing: The Answer Is in Your DNA," will run on Wednesday, March 30, 2016 7:30 am (ET/PT) and again on Wednesday, April 6, 2016 7:30 am (ET/PT).

Individuals diagnosed with hereditary cancer syndromes such as Lynch Syndrome and Hereditary Breast and Ovarian Cancer Syndrome are at significantly higher risk of developing cancer than the general population. In this special episode of Access Health, viewers will hear from experts in the field of hereditary cancer, including certified genetic counselor Marianne Lotito and Angelina Jolie’s breast surgeon, Dr. Kristi Funk.

With regard to the show, Dr. Kristi Funk, M.D., said, "I am excited to be a part of this special episode of Access Health which educates individuals on the importance of cancer family history and the role genetic testing plays in understanding both individual cancer risk and related medical management options."

The program discusses the value of knowing personal and family cancer history, follows the inspirational journeys of two families affected by hereditary cancer and highlights how genetic testing positively impacted their lives and that of their families. The program also discusses hereditary cancer resources, including Myriad’s Hereditary Cancer Quiz that helps individuals learn about their hereditary cancer risk. This quiz is an online resource that helps individuals evaluate their personal/family cancer history and whether they may be candidates for genetic testing. It then generates a family history overview that can be shared with healthcare providers.

"We are very excited to support this Lifetime program, which is a broad, powerful resource for people seeking answers on a variety of important health questions related to genetic testing and cancer," said Bret Christensen, general manager, Preventive Care, Myriad Genetic Laboratories. "Our goal is to educate the public and to empower all Americans to live healthier lives. The Hereditary Cancer Quiz is a quick way for people to determine if they have any red flags for hereditary cancer."

To take the Hereditary Cancer Quiz, please visit View Source

Celator® Pharmaceuticals Announces Business Update and Fourth Quarter and Full Year 2015 Financial Results

On March 21, 2016 Celator Pharmaceuticals, Inc. (Nasdaq: CPXX), a biopharmaceutical company that is transforming the science of combination therapy and developing products to improve patient outcomes in cancer, reported business highlights and financial results for the fourth quarter and year ended December 31, 2015 (Press release, Celator Pharmaceuticals, MAR 21, 2016, View Source [SID:1234509765]).

"In 2015, Celator continued to meet important milestones with VYXEOS and the CombiPlex platform," said Scott Jackson, chief executive officer of Celator. "Recently, we announced positive results from our Phase 3 trial in patients with high-risk (secondary) acute myeloid leukemia (AML), comparing VYXEOS to the long established standard of care, known as 7+3. We submitted results from the Phase 3 trial to the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting. Based on these results, we expect to submit a New Drug Application to the FDA in the third quarter of this year. In addition, in 2015 we embarked on a broader clinical development program via several trials evaluating VYXEOS in other AML patient populations as well as other blood cancers. Lastly, we were pleased to report data from novel combinations involving targeted therapies based on our CombiPlex technology platform. This is a very exciting and transformational time for Celator."

The following are expected milestones for VYXEOS:

3Q 2016 – New Drug Application (NDA) submission
1Q 2017 – Marketing Authorization Application (MAA) submission
Mid-2017 – Prescription Drug User Fee Act (PDUFA) date (assuming FDA priority review)
1Q 2018 – Committee for Medicinal Products for Human Use (CHMP) opinion date
Recent Business and Fourth Quarter 2015 Highlights

VYXEOS (CPX-351)

In March, Celator announced that the Phase 3 trial for VYXEOS in patients with high-risk (secondary) acute myeloid leukemia demonstrated a statistically significant improvement in overall survival.

In January, Celator announced participation in a Cardiff University clinical trial in patients with AML or High-Risk Myelodysplastic Syndrome (HR-MDS).

In December, data were presented on VYXEOS at the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting. Most notable were data presented showing VYXEOS did not prolong the QT/QTc interval, a positive safety outcome. The drugs remain encapsulated in the nano-scale delivery vehicle while circulating in the plasma ( > 97% over the first 24 hours), which allows the drugs to be delivered directly to leukemia cells at the synergistic 5:1 molar ratio. The trial included patients with newly diagnosed AML, relapsed/refractory AML and relapsed/refractory ALL. Responses were seen in each of the three acute leukemia patient populations.

Also in December at the ASH (Free ASH Whitepaper) meeting we presented data on health resource utilization (HRU) assessments from our previously published randomized Phase 2 trial comparing first-line treatment with VYXEOS to the 7+3 regimen, in newly diagnosed older patients (age 60-75) with AML. A number of outcomes (such as fewer inductions to respond, more patients receiving consolidation on an outpatient basis, improvement in the ratio of median event-free survival days to median hospital days) were favorable for VYXEOS compared to 7+3.

In October, VYXEOS was recognized with the Nanomedicine Award 2015. This award recognizes projects or products that have been developed using innovative solutions based on nanotechnology.
Technology Platform

In October, positive results were presented from our CombiPlex technology platform applied to drug combinations incorporating molecularly targeted agents (MTAs) at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). The successful application of this technology to molecularly targeted agents across a wide range of drug classes makes a compelling data package that we believe will be instrumental in pursuing R&D collaborations with pharmaceutical companies.
General Business

In November, Celator announced it was approved to sell $1.8 million of its net operating losses and unused research and development (R&D) credits under the New Jersey Technology Business Tax Certificate Transfer Program for the year 2015, for which the company received $1.7 million in non-dilutive financing.

In November, Celator announced a notice of allowance of claims by the United States Patent and Trademark Office for the patent "Compositions for Delivery of Drug Combinations." This patent covers the Company’s proprietary CombiPlex technology, and the allowed claims increase the scope of drug delivery vehicles covered by the patent.
Financial Highlights

Cash Position: Cash and cash equivalents as of December 31, 2015 were $23.3 million, compared to $32.4 million as of December 31, 2014. During the first quarter of 2016, the Company sold 1,353,900 shares of common stock through an at-the-market (ATM) equity offering program for net proceeds of $9.8 million. Management believes that the cash and cash equivalents at December 31, 2015, and the cash generated to date from sales under the ATM will be sufficient to meet estimated working capital requirements and fund planned operations into the second quarter of 2017.

R&D Expenses: Research and development expenses increased to $2.8 million for the three months ended December 31, 2015 from $2.7 million for the same period in 2014. For the year ended December 31, 2015 research and development expenses decreased to $11.8 million from $11.9 million for the same period in 2014. The full year decrease in R&D expenses was largely due to a decrease in clinical and regulatory activities during the year related to the Phase 3 trial of VYXEOS as the trial was fully enrolled, offset by an increase in expenses relating to our work on the CombiPlex platform.

G&A Expenses: General and administrative expenses increased to $1.9 million for the three months ended December 31, 2015 from $1.8 million for the same period in 2014. For the year ended December 31, 2015 general and administrative expenses increased to $7.7 million from $7.3 million for the same period in 2014. The increase was primarily attributable to increases in compensation and stock option expense, investor relations and consulting.

Net Loss: Net loss increased to $4.4 million for the three months ended December 31, 2015 from $2.4 million for same period in 2014. For the year ended December 31, 2015 net loss increased to $19.3 million from $16.9 million for the same period in 2014. The increase in net loss was primarily attributable to increased interest expense and a reduction in income tax benefit.