On June 10, 2015 ARIAD and Paladin Labs reported that ARIAD has granted Paladin exclusive rights to distribute Iclusig (as ponatinib hydrochloride) in Canada for its newly approved indications (Press release, Ariad, JUN 10, 2015, View Source [SID:1234505387]). Paladin is focused on acquiring or in-licensing innovative pharmaceutical products for the Canadian market. Schedule your 30 min Free 1stOncology Demo! Health Canada recently approved Iclusig for the treatment of adult patients with all phases of chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for whom other tyrosine kinase inhibitor (TKI) therapy is not appropriate, including CML or Ph+ ALL that is T315I mutation positive, or where there is prior TKI resistance or intolerance. Iclusig will be made available through a controlled distribution program, whereby prescribers who have completed the certification procedure will be able to prescribe Iclusig. Know more, wherever you are: "Paladin has a proven track record of successfully commercializing innovative pharmaceuticals in Canada and will be a strong partner for us," said Marty J. Duvall, executive vice president and chief commercial officer of ARIAD. "Through this commercial distribution agreement, we are confident that Iclusig will become available for appropriate patients with Ph+ leukemias who otherwise would have limited treatment options available."
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Under the terms of the agreement, ARIAD will continue to be the Marketing Authorization Holder of Iclusig in Canada, and Paladin will be responsible for distribution, sales and marketing, medical affairs, and pricing and reimbursement activities. Paladin will book sales of Iclusig in Canada while ARIAD will supply packaged drug to Paladin.
"Iclusig has shown promising clinical evidence to address this serious unmet medical need," said Mark Beaudet, President of Paladin. "We are excited to add this important medicine to our core pharmaceutical-product offering in Canada through our collaboration with ARIAD."
CML is a cancer of the white blood cells that according to the Chronic Myelogenous Leukemia Society of Canada affects 1 in 100,000, with about 5,500 Canadians living with the disease. In 2010, more than 550 people in Canada were estimated to be diagnosed with CML, and 480 people were estimated to be diagnosed with ALL.
About Iclusig (as ponatinib hydrochloride)
Iclusig is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Iclusig was designed using ARIAD’s computational and structure-based drug design platform specifically to inhibit the activity of BCR-ABL. Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs.
Indications in Canada
ICLUSIG is indicated for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) for whom other tyrosine kinase inhibitor (TKI) therapy is not appropriate, including CML or Ph+ ALL that is T315I mutation positive or where there is prior TKI resistance or intolerance.
Marketing authorization with conditions is based on response rate. There are no trials demonstrating increased survival or improvement in symptoms with ICLUSIG. In the pivotal trial, the majority of the hematological responses occurred within 1 month. Consider discontinuing ICLUSIG if a hematological response has not been achieved by 3 months (90 days).
ICLUSIG for this indication has been issued marketing authorization with conditions, pending the results of studies to verify its clinical benefit. Patients should be advised of the conditional nature of the authorization.
Contraindications
Do not use in patients who are hypersensitive to ponatinib or to any ingredient in the formulation or component of the container. For a complete listing, see the DOSAGE FORMS, COMPOSITION AND PACKAGING section of the Product Monograph.
Do not use in patients who have unmanaged cardiovascular risk factors, including uncontrolled hypertension. Hypertension may contribute to the risk of arterial thrombotic events. Blood pressure should be monitored and managed to avoid hypertension.
Do not use in patients who are not adequately hydrated and with uncorrected high uric acid levels.
Serious Warnings and Precautions
ICLUSIG has serious warnings and precautions for: vascular occlusion, heart failure, hemorrhage, hepatotoxicity, myelosuppression, and pancreatitis.
ICLUSIG should only be prescribed and monitored by a physician who has completed the certification with the ICLUSIG Controlled Distribution Program and who is experienced in the use of antineoplastic therapy and in the treatment of CML or Ph+ ALL.
Vascular Occlusion (arterial and venous thrombosis and occlusions), occurred in 24% (129/530) of ICLUSIG-treated patients with and without cardiovascular risk factors (including patients less than 50 years old). In clinical trials, serious treatment-emergent arterial thrombosis (cardiovascular, cerebrovascular, and peripheral vascular) and occlusions were seen in 14% of the ICLUSIG-treated patients including fatal myocardial infarction, fatal cerebral infarction, stroke, disseminated intravascular coagulation, and arterial stenosis sometimes requiring urgent revascularization procedures. Some of these events occurred within 2 weeks of starting treatment with ICLUSIG. Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or consider discontinuation in patients who develop arterial thrombotic events.
Heart Failure (in some cases, fatal), including left ventricular dysfunction and ejection fraction decreases, occurred in 8% of ICLUSIG-treated patients, 5% of which were serious.
Hemorrhage events (some fatal) including intracranial hemorrhage, hemorrhagic gastritis, (fatal), hemorrhagic cerebral infarction (fatal). Most hemorrhagic events, but not all, occurred in patients with grade 4 thrombocytopenia.
Hepatotoxicity (including fatal acute hepatic failure) has been reported. Monitor hepatic function prior to and during treatment. Consider ICLUSIG dose interruption followed by dose reduction or discontinuation in patients with hepatotoxicity.
Myelosuppression (thrombocytopenia, neutropenia, and anemia).
Pancreatitis (7%) and elevations in amylase (2% grade 3 or greater) or lipase (12% grade 3 or greater) have been reported.
ICLUSIG has not been studied in patients with renal impairment.
Most Common Adverse Reactions
Overall, the very common adverse reactions (≥ 10%) were platelet count decreased, rash, dry skin, abdominal pain, neutrophil count decreased, headache, lipase increased, fatigue, constipation, myalgia, arthralgia, nausea, anemia, ALT increased, hypertension, and AST increased.
EISAI LAUNCHES ANTICANCER AGENT LENVIMA(R) (LENVATINIB MESYLATE) IN UNITED KINGDOM INDICATED FOR ADVANCED THYROID CANCER REFRACTORY TO RADIOACTIVE IODINE
On June 10, 2015 Eisai reported that its U.K. subsidiary Eisai Europe Ltd. has launched its in-house developed novel anticancer agent Lenvima (lenvatinib mesylate) indicated for the treatment of adult patients with progressive, locally advanced or metastaticdifferentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC) refractory to radioactive iodine (RAI) in the United Kingdom (Press release, Eisai, JUN 10, 2015, View Source [SID:1234505384]). Following the launch of Lenvima in the United Kingdom, Eisai plans to launch the agent in countries throughout Europe. Schedule your 30 min Free 1stOncology Demo! It is estimated that thyroid cancer affects more than 52,000 people in Europe each year. Differentiated thyroid cancer is the most common form of thyroid cancer and accounts for approximately 95% of all thyroid cancers. Although most differentiated thyroid cancers can be treated with surgery and radioactive iodine treatment, there are few treatment options available once the cancer has progressed, therefore it remains a disease with significant unmet medical needs.
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In a global Phase III study (the SELECT study) of Lenvima in differentiated thyroid cancer, Lenvima demonstrated a statistically significant extension in progression free survival and improved response rates compared to placebo 1. The most common Lenvima treatment-related adverse events were hypertension, diarrhea, fatigue or asthenia, decreased appetite, weight loss and nausea. Lenvima was granted an accelerated assessment by the European Medicines Agency, and was approved on May 28, 2015.
Discovered at Eisai’s Tsukuba Research Laboratories and developed in-house, Lenvima is an orally administered molecular targeted agent that selectively inhibits the activities of several different molecules including VEGFR, FGFR, RET, KIT and PDGFR. In particular, the agent simultaneously inhibits VEGFR,FGFR and also RET, which are especially involved in tumor angiogenesis and proliferation of thyroid cancer. Furthermore, Lenvima has been confirmed through X-ray co-crystal structural analysis to demonstrate a new binding mode (Type V) to VEGFR2, and exhibits rapid binding to the target molecule and potent inhibition of kinase activity, according to kinetic analysis2.
Lenvima was first launched in the United States indicated for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer in February 2015, and was subsequently launched in Japan for the treatment of unresectable thyroid cancer in May 2015. Eisai is aiming to launch the agent in over 20 countries in fiscal 2015. Furthermore, Eisai is conducting a global Phase III study of Lenvima in hepatocellular carcinoma as well as Phase II studies of Lenvima in several other tumor types such as renal cell carcinoma and non-small cell lung cancer.
In addition to providing Lenvima as a new treatment option for thyroid cancer, Eisai is committed to exploring the potential clinical benefits of Lenvima in order to further contribute to, and address the diverse needs of, patients with cancer and their families.
Cellular Biomedicine Group Enters Into Definitive Agreement to Acquire CD40LGVAX Vaccine and Related Technologies and Know-How Which Will Be Used in a Pending PD-1 Combination Clinical Trial in the U.S. for Non-Small Cell Lung Cancer (NSCLC)
On June 9, 2015 Cellular Biomedicine Group reported that it has entered into a definitive agreement to acquire from Blackbird Bio Finance ("BB") University of South Florida’s ("Licensor") next generation GVAX vaccine’s ("CD40LGVAX") related technologies and know-how for an initial consideration of $2.5 million in cash and $1.75 million in shares of the Company’s Common Stock (Filing, 8-K, Cellular Biomedicine Group, JUN 9, 2015, View Source [SID:1234505412]). The per share price will be based on the 20-day volume weighted average price ("VWAP") of the Company’s Common Stock upon the closing of the acquisition. CBMG will pay potentially more than $25 million in future milestones and royalty payments. As part of the transaction, CBMG will be the exclusive global licensee of the Licensor’s related technologies and know-how, the progeny manufacturing rights with access to a master vaccine bank originating from the University of South Florida ("USF").
The inventor of CD40LGVAX, Scott Antonia, MD, Ph.D. is currently the Department Chair of Thoracic Oncology and Program Leader of the Immuno-oncology Program at the Moffitt Cancer Center. Dr. Antonia ranks among the foremost experts in the world of immuno-oncology and is an active collaborator with large pharmaceutical companies. He is recognized as one of the world’s leading authorities in the treatment of lung cancer with immunotherapeutics and has recently joined the Company’s Scientific Advisory Board. Given the positive Phase I results of CD40LGVAX alone in non-small cell lung cancer (NSCLC), Dr. Antonia plans to combine the CD40LGVAX with a checkpoint inhibitor, anti-PD1 monoclonal antibody, Nivolumab, in a three patient lead-in Phase I clinical trial followed by a randomized Phase II clinical trial in the U.S. to evaluate the safety and efficacy of the combination in patients with Stage 4 unresectable non-small cell lung cancer. The clinical trials are expected to commence in the second half of 2015.
Dr. William (Wei) Cao, Chief Executive Officer of Cellular Biomedicine Group, commented: "This strategic acquisition will enable CBMG to broaden its product portfolio based on the acquired related technologies and know-how to augment our immuno-oncology platform portfolio, particularly cancer immunotherapy vaccine and combination technology platform. Fundamentally, it would transform CBMG into a global player with leading comprehensive cancer treatment programs. It should be noted that Dr. Antonia’s NSCLC advanced clinical programs using proprietary "off-the-shelf" vaccines, would be conducted in the United States with CBMG funding the vaccine supply. We are committed to deploying resources in the U.S. to support the clinical trials, serve U.S. patients and obtain eventual FDA regulatory approval. This represents a major milestone in our foray into the U.S. market. In addition, upon receiving the requisite regulatory approval, we will seek approval to conduct clinical trials in China with leading medical centers to serve China’s patients with lung cancer. We look forward to continuing to explore other international partnerships and licensing opportunities."
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ABOUT NSCLC
Based on the latest data available from NCCN Clinical Practice Guidelines in Oncology Non-Small Cell Lung Cancer (Version 4. 2014), an estimated 224,210 people in the United States were diagnosed with lung cancer in 2014, with an estimated 159,260 deaths occurring because of the disease. In China, 728,552 people were diagnosed with lung cancer in 2012, and 592,410 people in China died from lung cancer in 2012 (source: Chinese Cancer Registry annual report 2012 & GMCD40L Study Synopsis). NSCLC is relatively insensitive to chemotherapy and radiation therapy. Despite the advances of targeted therapies and recent breakthroughs with immune checkpoint inhibitors, such as anti-PD1 or PDL1 monoclonal antibody treatments, there are still significant unmet medical needs in NSCLC. CD40LGVAX vaccine, in combination with an anti-PD1 monoclonal antibody, may provide synergistic and improved clinical benefits in both PDL1 positive and negative patients.
ABOUT CD40LGVAX
CD40LGVAX is a vaccine in which irradiated allogeneic lung adenocarcinoma cells are combined with a bystander cell line transfected with hCD40L and hGM-CSF. The key differentiator is the transfection of the bystander cell line with GM-CSF and CD40L. Both GM-CSF and CD40L can activate dendritic cells (DC). Nivolumab, an anti-PD-1 monoclonal antibody, enhances cytotoxic T cell activity by blocking the interaction between PD-1 and its receptors. The vaccine has previously been tested in a Phase I trial, and has shown encouraging efficacy and toxicity profile. In the United States, the Food and Drug Administration ("FDA") has approved Nivolumab for treatment of patients with melanoma and advanced squamous NSCLC who have progressed on or after platinum-based chemotherapy. About 25% to 30% of all NSCLC are squamous. By combining CD40LGVAX with an anti-PD1 monoclonal antibody, the approach is expected to further boost the body’s immune system to kill cancer cells. Given the strength of both products and potential synergistic mechanism of action, this potential combination may provide more clinical benefit to NSCLC than either product alone.
6-K – Report of foreign issuer [Rules 13a-16 and 15d-16]
On JUNE 9, 2015 Cellectis reported in order to comply with NASDAQ financial practices, is publishing for the first time its 1st quarter results (Filing, 6-K, Cellectis, JUN 9, 2015, View Source [SID:1234505385]).
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Cellectis previously published consolidated financial statements for the first six months of 2014 and for the full year 2014. The Company did not publish financial statements for first half-year and full year 2014. Cellectis did not have consolidated financial statements for the 1st and 3rd quarters 2014. Therefore, no comparative 2014 figures will be presented for 1st and 3rd quarters in 2015. Cellectis will publish full quarterly comparative figures starting 2016.
Consolidated financial statements have been prepared in accordance with International Financial Reporting Standards, or IFRS, as issued by the International Accounting Standards Board ("GAAP").
First Quarter 2015 Financial Results
Revenues and Other Income: Total revenues and other income were of €9.2 million for the first quarter 2015 (€26.5 million for FY2014) and mainly comprised €7.9 million of collaboration revenues (€11.9 million for FY2014) and €0.4 million of license revenues (€7.3 million for FY2014).
Total Operating Expenses and Other Operating Income: Total operating expenses and other operating income for the first quarter of 2015 were of €12.8 million (€31.7 million for FY2014).
R&D Expenses: Research and development expenses for the first quarter of 2015 were of €5.6 million (€14.4 million for FY2014). These expenses mainly consisted of personnel expenses (€3.5 million), external purchases and other expenses (€2.1 million).
Research and development expenses for the first quarter also reflect the impact of social charges related to stock-options and free shares granted during the first quarter (€1.9 million).
SG&A Expenses: Selling, general and administrative expenses were of €7.2 million for the first quarter 2015 (€13.1 million for FY2014). These expenses mainly related to personnel expenses (€4.9 million), and to external purchases and other expenses (€2.3 million). Selling, general and administrative expenses for the first quarter also reflect the impact of social charges related to stock-options and free shares granted during the first quarter (€3.3 million). For the first three months 2015, the non–recurring IPO expenses amounted to €0.5 million.
Financial Gain: Financial gain was of €9.9 million for the first quarter 2015 (€7.1 million for FY2014), which is mainly attributable to a favorable Euro-Dollar exchange rate applied to U.S. dollar-denominated cash and cash equivalents during the first quarter of 2015.
Net Income (Loss): Net income was of €6.3 million, or €0.23 per share, for the first quarter of 2015 (net loss of €1.0 million, or €0.00 per share, for FY2014). Adjusted net income for the first quarter of 2015 was €7.1 million, or €0.23 per share. Adjusted net income for the first quarter of 2015 excludes a non-cash stock-based compensation expense of €0.8 million. Please see "Note Regarding Use of Non-GAAP Financial Measures" for a reconciliation of GAAP net income to adjusted net income.
Cash Position: Cash and cash equivalents include cash, bank accounts, money market funds and fixed bank deposits that meet the definition of a cash equivalent. As of March 31, 2015, Cellectis had €118.4 million in cash and cash equivalents compared to €112.3 million as of December 31, 2014. Our initial public offering closed on March 30, 2015 and as of March 31, 2015, the €196.8 million of net proceeds from the initial public offering are classified under Other Current Assets. We believe that our cash and cash equivalents, together with the net proceeds from our initial public offering and our cash flow from operations (including payments we expect to receive pursuant to our collaboration agreements) and government funding of research programs will be sufficient to fund our operations through at least 2017. However, we may require additional capital for the further development of our existing product candidates and may also need to raise additional funds sooner to pursue other development activities related to additional product candidates.
Clinical Experts Report on How Varian Technology Can Be Used for the Precise, Noninvasive, Simultaneous Treatment of Multiple Metastases in the Brain, Spine, Head & Neck, and Lung
On June 9, 2015 Varian Medical Systems reported RapidArc Radiosurgery, a term for volumetric modulated arc radiosurgery delivered using a medical linear accelerator (linac) from Varian Medical Systems (NYSE: VAR), enables the precise and simultaneous treatment of multiple metastases in the brain, spine, head & neck, or lung, according to four notable clinical experts who spoke yesterday at a Varian-sponsored symposium at the 12th International Stereotactic Radiosurgery Society (ISRS) Congress taking place here this week (Press release, InfiMed, JUN 9, 2015, View Source [SID:1234505381]).
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Clark C. Chen, MD, PhD, co-director of neurological oncology and chief of stereotactic radiosurgery at the University of California, San Diego, offered a neurosurgeon’s perspective on the clinical use of surface imaging to guide RapidArc Radiosurgery for the treatment of brain metastases. He favors this more targeted approach over whole-brain radiotherapy for patients with a limited number of brain metastases to avoid the neurocognitive decline that is associated with the latter.
"The Varian TrueBeam is a powerful linear accelerator that allows precise and efficient delivery of high dose radiation to multiple brain metastases in a remarkably efficient manner," Chen said. His team also uses an optical surface image tracking device during treatment to help ensure accurate radiation delivery. "The combination of surface image tracking and RapidArc Radiosurgery allows us to treat patients with a level of efficiency that we could not achieve previously," he said.
Evan Thomas, MD, PhD, postdoctoral research fellow in the Department of Radiation Oncology at the University of Alabama at Birmingham (UAB), talked about the UAB approach to RapidArc Radiosurgery planning, which makes use of key features of Varian’s Edge and TrueBeam STx platforms for image-guided stereotactic radiosurgery (SRS), including Varian’s HD120 high-definition multileaf collimator for fine beam shaping and the High Intensity Mode for delivering high doses quickly.1 "Multiple refinements and iterations in the UAB technique have enabled us to reliably duplicate Gamma Knife plan quality on TrueBeam STx," Thomas said.2
At the Henry Ford Health System (HFHS) in Detroit, SRS treatments are delivered using Varian’s Edge radiosurgery system. Ian Lee, MD, neurosurgeon with the Hermelin Brain Tumor Center at HFHS, raised the question of how to determine whether surgery, radiosurgery, or both are indicated in cases of metastatic brain cancer. The HFHS uses a multidisciplinary tumor board to make those determinations as a team. He presented a broad range of metastatic brain cancer cases that were treated with stereotactic radiosurgery. "SRS is usually the treatment of choice for oligometastatic disease," he said, referring to patients with multiple brain metastases.
Farzan Siddiqui MD, PhD, director of head and neck radiation oncology at HFHS, described soon-to-be-published data on the precision and accuracy of the Edge system for radiosurgery, showing his institution’s findings of sub-millimeter accuracy for each of the system’s component parts.3 In addition to several metastatic brain tumor cases, Siddiqui presented about cases where the Edge system was used to deliver RapidArc stereotactic body radiotherapy (SBRT) –a medical term for radiosurgery of non-cranial targets—to simultaneously treat multiple metastatic lesions in the spine, lung or head & neck. "The Edge radiosurgery system has been shown to possess high accuracy localization and meets requirements for precisely treating patients with tumors in the various sites using SRS/SBRT-based techniques," he reported.