On November 14, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of two Type II variation applications to the European Medicines Agency (EMA) seeking approval for the expanded use of IMBRUVICA (ibrutinib) (Press release, Johnson & Johnson, NOV 14, 2018, View Source [SID1234531316]). One application seeks to include use of ibrutinib in combination with obinutuzumab in previously untreated adults with chronic lymphocytic leukaemia (CLL) and to add long-term follow-up data from the existing label studies RESONATETM (PCYC-1112) and RESONATETM-2 (PCYC-1115). The second is for use of ibrutinib plus rituximab for the treatment of previously untreated and relapsed/refractory adults with Waldenström’s macroglobulinemia (WM).

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"Today’s news brings us one step closer to potentially offering ibrutinib in new combinations for patients where unmet needs still persist," said Dr. Catherine Taylor, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag Limited. "Ibrutinib continues to demonstrate clinical benefit over the long term for a broad group of patients living with blood cancer, and we look forward to working with relevant authorities to secure approval of these new combinations."

Ibrutinib, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialised by Janssen Biotech, Inc., and Pharmacyclics LLC, an AbbVie company.

The CLL submission is supported by positive results from the Phase 3 iLLUMINATE (PCYC-1130) study which investigated ibrutinib in combination with obinutuzumab versus chlorambucil plus obinutuzumab in patients with newly diagnosed CLL.1 Study findings from iLLUMINATE will also be featured as an oral presentation (abstract #691), whilst further analysis of RESONATETM and RESONATETM-2 results in comparison with real-world evidence databases (abstract #4427) will be included at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place in San Diego next month.1,2 A supplemental New Drug Application (sNDA) which was also recently submitted to the U.S. Food and Drug Administration (FDA) received Priority Review.

In WM, the submission is supported by data from the Phase 3 iNNOVATE (PCYC-1127) study evaluating ibrutinib in combination with rituximab, versus rituximab with placebo, in patients with previously untreated and relapsed/refractory WM.3 Follow-up efficacy and safety findings from the iNNOVATE study will also be presented at ASH (Free ASH Whitepaper) 2018 (abstract #149).4 In August 2018, the FDA approved ibrutinib in combination with rituximab for the treatment of WM based on the data from iNNOVATE.5

Additional information about both studies can be found at www.ClinicalTrials.gov (NCT02264574 and NCT02165397).6,7

#ENDS#

About ibrutinib

Ibrutinib is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B-cells.8 By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells, thereby delaying progression of the cancer.9

Ibrutinib is currently approved in Europe for the following uses:10

Chronic lymphocytic leukaemia (CLL): As a single agent for the treatment of adult patients with previously untreated CLL, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy.
Mantle cell lymphoma (MCL): Adult patients with relapsed or refractory mantle cell MCL.
Waldenström’s macroglobulinemia (WM): Adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy.
The most common adverse reactions seen with ibrutinib include diarrhoea, neutropenia, haemorrhage (e.g., bruising), musculoskeletal pain, nausea, rash, and pyrexia.10

For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.

About CLL

CLL is typically a slow-growing blood cancer of the white blood cells.11 The overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year with rates amongst men and women approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively.12 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.13

CLL is a chronic disease; median overall survival ranges between 18 months and more than 10 years, according to the stage of disease.14 The disease eventually progresses in the majority of patients, and patients are faced with fewer treatment options with each relapse. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.

About Waldenström’s macroglobulinemia

Waldenström’s macroglobulinemia (WM) is a rare form of non-Hodgkin’s lymphoma (NHL).15 It causes overproduction of a protein called monoclonal immunoglobulin M (IgM) antibody, which causes a thickening of the blood.16 Incidence rates among men and women in Europe are approximately 7.3 and 4.2 per million persons, respectively.17 The causes of WM are unknown, with it typically affecting older adults and being slightly more common in men than women.15,17

On November 14, 2018 Five Prime Therapeutics, Inc. (Nasdaq: FPRX), a biotechnology company discovering and developing innovative immuno-oncology protein therapeutics, reported it initiated patient dosing in a Phase 1 clinical trial of FPT155, a first-in-class CD80 fusion protein (Press release, Five Prime Therapeutics, NOV 14, 2018, View Source [SID1234531315]). The trial was initiated in Australia.

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"We are pleased to initiate patient dosing for FPT155, our first-in-class CD80-Fc fusion protein, which is engineered to activate T cells through multiple pathways," said Helen Collins, M.D., Senior Vice President and Chief Medical Officer of Five Prime. "In vivo, FPT155 demonstrates strong single-agent activity in multiple preclinical models, including some that are generally resistant to immune-modulating therapy. We look forward to testing FPT155 in the clinic to see if it has the potential to improve outcomes across multiple tumor indications where new treatment options are needed."

"FPT155 is further evidence of Five Prime executing on the strategy of leveraging our IND engine as a source of competitive advantage in developing first-in-class agents that have the potential to demonstrate single-agent activity or activity in tumors that typically do not respond to checkpoint inhibitors," said Aron Knickerbocker, Chief Executive Officer of Five Prime Therapeutics. "Beyond FPT155, this strategy can be seen across our robust pipeline, including with cabiralizumab, bemarituzumab and FPA150. These drug candidates target or engage multiple cells in the tumor microenvironment, including tumor cells, effector T cells, macrophages and NK cells."

The Phase 1a/1b open-label, multicenter, dose escalation, dose exploration and dose expansion study will evaluate the safety and tolerability of FPT155 in patients with advanced solid tumors. The Phase 1a dose escalation portion of the trial will characterize the safety and pharmacokinetic (PK)/pharmacodynamic (PD) profile of FPT155 and will identify a recommended dose for the Phase 1b portion of the trial. During the dose escalation, Five Prime will also open an exploratory cohort to investigate FPT155 monotherapy in select tumor types with high unmet need. The Phase 1b portion of the trial is intended to further characterize the safety, PK/PD profile, and preliminary efficacy of FPT155.

About FPT155

FPT155 is a first-in-class CD80 fusion protein that (i) directly engages CD28 to enhance its co-stimulatory T-cell activation activity without inducing super agonism, and (ii) blocks CTLA-4 from competing for endogenous CD80, allowing CD28 signaling to prevail in T-cell activation in the tumor microenvironment. FPT155 has also demonstrated its ability to retain anti-tumor activity independent of its engagement with CTLA-4, suggesting a differentiated mechanism of action from CTLA-4-blocking antibodies. Studies in preclinical models suggest FPT155 has the potential to be a potent T-cell co-stimulator with strong monotherapy anti-tumor activity.

On November 14, 2018 Agilent Technologies Inc. (NYSE: A) reported it has completed the acquisition of ACEA Biosciences Inc. (ACEA), a developer of cutting-edge cell analysis tools, for $250 million in cash (Press release, Agilent, NOV 14, 2018, View Source [SID1234531314]). This acquisition brings together two pioneers in cellular function and metabolism measurements focused on real-time, live cell analyses.

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ACEA has developed two ground-breaking platforms that are complementary to Agilent’s current portfolio. The ACEA xCELLigence RTCA technology is a unique impedance platform for label-free, real-time cellular function measurements used in immuno-oncology, pre-clinical drug discovery and development, as well as in basic academic research. This technology is complemented by the introduction in recent years of the NovoCyte and NovoCyte Quanteon portfolio of high performance bench top flow cytometry systems.

ACEA also markets a clinical configuration of the NovoCyte platform, currently commercialized in China. This provides a unique opportunity in combination with Agilent’s Reagent Partnership business within Agilent’s Diagnostics and Genomics Group which provides reagents for flow cytometry.

"The Agilent and ACEA teams are united by a common goal to provide the most innovative high-performance solutions for cell analysis," said Todd Christian, Vice President & General Manager of Agilent’s Cell Analysis Division. "We are excited for the opportunities we have as a newly combined team to provide the most advanced tools for scientists performing cell analysis workflows."

ACEA is Agilent’s second acquisition this year in the cell analysis space. In January, Agilent acquired Luxcel Biosciences, a developer of real-time fluorescence plate-reader based in vitro cell assay kits. Cell analysis is a key area of strategic focus for Agilent.

ACEA was founded in 2002 and has its headquarters in San Diego and a large manufacturing and R&D footprint in Hangzhou, China. More than 2,500 ACEA instruments have been placed globally and have been used in more than 1,800 peer-reviewed publications.

On November 14, 2018 Blue Earth Diagnostics, a molecular imaging diagnostics company, reported that a presentation related to the clinical use of 18F-fluciclovine in adults with glioma will be occurring at the upcoming Society for Neuro-Oncology (SNO) Annual Scientific Meeting, being held November 15 – 18, 2018 in New Orleans, La (Press release, Blue Earth Diagnostics, NOV 14, 2018, View Source [SID1234531313]). Blue Earth Diagnostics is investigating the potential use of 18F-fluciclovine in adults for the detection and continuing assessment of glioma.

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The presentation listed below highlights the investigational use of 18F-fluciclovine, as an adjunct to magnetic resonance imaging (MRI), in adults with glioma.

Friday, November 16, 2018

Session Type: Poster Session
Session Title:

A Blinded Image Evaluation Study to Determine the Diagnostic Efficacy of 18F- fluciclovine PET, as an Adjunct to MRI Imaging, in Adults with Glioma

Presenter: Matthew P. Miller, PhD, Blue Earth Diagnostics
Poster Number: NIMG-01
Abstract ID: 506064
Presentation Time: 7:30 – 9:30 p.m. CT

Axumin (fluciclovine F 18) injection is FDA-approved for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment. The safety and efficacy of 18F-fluciclovine PET imaging in glioma have not been established.

U.S. Indication and Important Safety Information About Axumin

INDICATION

Axumin (fluciclovine F 18) injection is indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out recurrent prostate cancer and a positive image does not confirm its presence. The performance of Axumin seems to be affected by PSA levels. Axumin uptake may occur with other cancers and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation, is recommended.
Hypersensitivity reactions, including anaphylaxis, may occur in patients who receive Axumin. Emergency resuscitation equipment and personnel should be immediately available.
Axumin use contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling practices should be used to minimize radiation exposure to the patient and health care providers.
Adverse reactions were reported in ≤ 1% of subjects during clinical studies with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia.
To report suspected adverse reactions to Axumin, call 1-855-AXUMIN1 (1-855-298-6461) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Full Axumin prescribing information is available at www.axumin.com.

About 18F-fluciclovine PET in Glioma

18F-fluciclovine PET is a diagnostic imaging radiopharmaceutical for PET imaging that consists of a synthetic amino acid labeled with the radioisotope F 18, enabling the visualization of the increased amino acid transport that occurs in malignant tumors. 18F-fluciclovine, under the trade name Axumin, is approved by the U.S. Food and Drug Administration (FDA) for PET imaging in men with biochemically recurrent prostate cancer. It is also under investigation by Blue Earth Diagnostics for use in adults for the detection and continuing assessment of glioma. 18F-fluciclovine has been granted Orphan Drug status by both the FDA and the European Medicines Agency for the diagnosis of glioma. The compound was invented at Emory University in Atlanta, Ga., with much of the fundamental clinical development work carried out by physicians at Emory University’s Department of Radiology and Imaging Sciences.

About Glioma

Glioma, the most commonly occurring type of primary brain tumor, is a serious and life-threatening condition. Cancer of the brain and central nervous system (CNS) is the twelfth most common cause of cancer death worldwide. Glioma accounts for about 25% of all brain tumors, and 80% of all malignant brain tumors. The most aggressive form of glioma, glioblastoma multiforme, is associated with significant morbidity and mortality with relatively low 5-year survival estimates after diagnosis. Current treatment options for patients with glioma include surgery, radiation and chemotherapy. Accurate evaluation of the location and extent of a glioma tumor is essential before or during surgery and radiotherapy and in assessing the continuing status of the disease. The detection and assessment of gliomas typically involves magnetic resonance imaging (MRI), which may be complemented by metabolic imaging using an appropriate amino acid-based PET radiopharmaceutical, as recommended in the Response Assessment in Neuro-Oncology (RANO) working group and European Association for Neuro-Oncology (EANO) guidelines.1

On November 14, 2018 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported the plenary presentation of updated ZW25 clinical data by Murali Beeram, MD, a clinical investigator at the START Center for Cancer Care, San Antonio, Texas (Press release, Zymeworks, NOV 14, 2018, View Source [SID1234531312]). Data from Zymeworks’ ongoing multi-center Phase 1 study showed single agent ZW25, a bispecific antibody, induced anti-tumor activity and was well tolerated in heavily pretreated patients with a variety of HER2-expressing cancers.

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"Today we report, for the first time, the durability of ZW25’s anti-tumor activity," said Ali Tehrani, Ph.D., President and CEO of Zymeworks. "With a median of over six months of progression-free survival in these heavily pretreated patients, these data further support our previously-communicated clinical strategy which includes registration-enabling studies for single-agent ZW25 in gastrointestinal-related cancers where the unmet need is so great worldwide."

ZW25 Clinical Results Presented Today

The plenary presentation includes all 24 gastroesophageal and other cancer patients treated at the Phase 2 recommended dose, of which 17 were response-evaluable (defined as having measurable disease and at least one tumor restaging) at the time of data cut-off. Of these 17 patients, eight had gastroesophageal cancers, four had colorectal cancer and five had other HER2-expressing cancers including gall bladder, cholangiocarcinoma, cervical, fallopian tube and salivary gland. The participants in the study were heavily pretreated with a median of three prior cancer treatments.

The overall disease control rate (DCR), which includes patients with partial responses and stable disease was 82%. There were seven partial responses (41%), seven stable disease (41%) and three progressive disease (18%). The median progression-free survival (mPFS) in all 24 patients was 6.21 months (95% CI 1.94-9.33).

"To observe this level of activity across so many different tumor types is quite compelling," said Murali Beeram, MD. "These were heavily pretreated patients who had essentially run out of therapeutic options, so for them to respond so favorably is indeed encouraging."

In the eight gastroesophageal cancer patients, who had a median of four prior systemic treatments, the response rate was 50%. In the four colorectal and five other HER2-expressing cancer patients the response rate was 33%. Anti-tumor activity was assessed per RECIST every eight weeks.

In the study, ZW25 was well tolerated. All treatment-related adverse events were Grade 1 or 2 with the exception of one patient with Grade 3 fatigue, and no treatment-related serious adverse events were seen. There were no Grade 4 or 5 adverse events. The most common adverse events (25% or greater) were diarrhea, infusion reaction and nausea.

"The favorable tolerability we have seen with ZW25 supports its use as both a single agent and in combination with approved anti-cancer agents," said Diana Hausman, MD, Zymeworks’ Chief Medical Officer. "We are excited to be advancing ZW25’s development and have plans to explore its efficacy in a number of tumor types, including gastroesophageal and breast cancer."

Plenary Presentation Details

The presentation is part of the Symposium on Molecular Targets and Cancer Therapeutics sponsored by the European Organization for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

Title: "Single Agent Activity of ZW25, a HER2-Targeted Bispecific Antibody, in HER2-Expressing Gastroesophageal and Other Cancers"

Session: Proffered papers, Plenary Session 2, Abstract 6

Time: Wednesday November 14, 3:45 pm GMT

Location: Auditorium

About the Trial

Zymeworks’ adaptive Phase 1 study has three parts. Enrollment in the first portion of the study (the dose-escalation phase) has been completed. The recommended single-agent dose was determined to be 20 mg/kg once every two weeks or 10 mg/kg weekly. In the second part of the study (the cohort expansion phase), additional patients are being enrolled to further assess ZW25’s single-agent tolerability and anti-tumor activity against a variety of cancer types in different settings. The third part of the study (the combination phase) is underway and is evaluating ZW25 in combination with selected chemotherapy agents in gastroesophageal and breast cancer patients with HER2 high or lower HER2 expression levels.

About ZW25

ZW25 is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function and has led to encouraging anti-tumor activity in patients. Zymeworks is developing ZW25 as a HER2-targeted treatment option for patients with any solid tumor that expresses HER2. The FDA has granted Orphan Drug Designation to ZW25 for the treatment of both gastric and ovarian cancers.

About the Azymetric Platform

The Azymetric platform enables the transformation of monospecific antibodies into bispecific antibodies, giving them the ability to simultaneously bind two different targets. Azymetric bispecific technology enables the development of multifunctional biotherapeutics that can block multiple signaling pathways, recruit immune cells to tumors, enhance receptor clustering and degradation, and increase tumor-specific targeting. These features are intended to enhance efficacy while reducing toxicities and the potential for drug-resistance. Azymetric bispecifics have been engineered to retain the desirable drug-like qualities of naturally occurring antibodies, including low immunogenicity, long half-life, and high stability. In addition, they are compatible with standard manufacturing processes with high yields and purity with the potential to significantly reduce drug development costs and timelines.