On January 19, 2016 Baxalta Incorporated (NYSE:BXLT), a global biopharmaceutical leader dedicated to delivering transformative therapies to patients with orphan diseases and underserved conditions, reported that the European Commission has granted Marketing Authorization for use of ONCASPAR as a combination therapy in acute lymphoblastic leukaemia (ALL) in paediatric patients from birth to 18 years, and adult patients (Press release, Baxalta, JAN 19, 2016, View Source [SID:1234508806]).

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With this approval, Baxalta is authorized to market ONCASPAR in the 28 member countries of the European Union (EU), as well as Iceland, Liechtenstein and Norway. The drug is already licensed to market in Argentina, Belarus, Germany, Kazakhstan, Poland, Russia, Ukraine and the United States.

"ONCASPAR has been used as an integral component of the treatment regimen for paediatric and adult patients with ALL for many years, in Europe, and worldwide," said Prof. Dr. med. Martin Schrappe, director of the department of general paediatrics at the Schleswig-Holstein University Hospital in Kiel, Germany. "Today’s marketing authorization will ensure that more patients across the EU will benefit from access to ONCASPAR as part of a standard of care regimen."

With this authorization, ONCASPAR will provide an important treatment option for more European patients with this rapidly progressing cancer of the white blood cells responsible for up to 80 percent of childhood leukaemia cases – the most common type of childhood cancer. However, ALL is not only a childhood cancer but can also occur in adults. Adult ALL accounts for approximately 40 percent of the annual incidence.2

"For more than two decades, ONCASPAR has fulfilled a clear need for an effective and well-tolerated treatment for ALL patients worldwide. This European marketing authorization allows Baxalta to expand the use of ONCASPAR, improving treatment outcomes for all patients in the EU," said David Meek, executive vice president and president, Oncology, Baxalta. "This approval is important as we strive to make a difference in the lives of people living with cancer in all parts of the world."

About ONCASPAR (pegaspargase) in the EU

ONCASPAR is indicated as a component of antineoplastic combination therapy in acute lymphoblastic leukaemia (ALL) in paediatric patients from birth to 18 years, and adult patients.3

Contraindications3

Hypersensitivity to the active substance or to any of the excipients
Severe hepatic impairment (bilirubin > 3 times upper limit of normal [ULN]; transaminases > 10 times ULN)
History of serious thrombosis with prior L-asparaginase therapy
History of pancreatitis, including the related to previous asparaginase therapy
History of serious hemorrhagic events with prior L-asparaginase therapy
EU Important Safety Information

ONCASPAR is indicated as a component of antineoplastic combination therapy in acute lymphoblastic leukaemia (ALL) in paediatric patients from birth to 18 years, and adult patients.

ONCASPAR is contraindicated in patients with severe hepatic impairment (defined as bilirubin > 3 times upper limit of normal [ULN]; transaminases > 10 times ULN), a history of serious thrombosis with prior L asparaginase therapy, a history of pancreatitis, including the related to previous asparaginase therapy and those with a history of serious hemorrhagic events with prior L asparaginase therapy.

Anaphylaxis or serious allergic reactions can occur; therefore, patients should be observed for one hour after administration. Discontinue ONCASPAR in patients with serious allergic reactions. Patients with abdominal pain should be evaluated for evidence of pancreatitis. Discontinue ONCASPAR in patients with pancreatitis. ONCASPAR should also be discontinued in patients with serious thrombotic events.

Glucose intolerance, in some cases irreversible, can occur; serum glucose should be monitored. Coagulopathy and hepatotoxicity can occur; appropriate monitoring should be performed.

The most common adverse reactions with ONCASPAR (=2%) are allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, central nervous system (CNS) toxicity, thrombosis, coagulopathy, hyperbilirubinemia and elevated transaminases.

Hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) has been reported in patients exposed to ONCASPAR.

Oncaspar may possess immunosuppressive activity. It is therefore possible that use of this medicinal product promotes infections in patients.

Combination therapy with Oncaspar can result in severe hepatic toxicity and central nervous system toxicity. Caution is required when Oncaspar is given in combination with other hepatotoxic substances, especially if there is preexisting hepatic impairment. In this case, patients should be monitored for liver impairment.

In the presence of symptoms of hyperammonemia (e.g. nausea, vomiting, lethargy, irritation), ammonia levels should be monitored closely.

Labeling may differ by country registration. Please refer to your country specific labeling for detailed information.

About Acute Lymphoblastic Leukaemia1

Acute lymphoblastic leukaemia (ALL) is a rare, fast-growing cancer of the white blood cells, and each year there are approximately 4,000-5,000 new cases in Europe and the United States, respectively. The disease is the most common childhood cancer and is responsible for more than 80 percent of childhood leukaemia cases. The five-year paediatric survival rate has climbed to more than 80 percent with modern therapies.

On January 19, 2016 Advaxis, Inc. (NASDAQ:ADXS), a clinical stage biotechnology company developing cancer immunotherapies, reported that it has added two more patents to its growing patent portfolio (Press release, Advaxis, JAN 19, 2016, View Source [SID:1234508805]). The first patent, European Patent No. 1804831, expands the composition of matter claims covering HER-2 tumor antigens. The second patent, U.S. Patent No. 9,226,958, expands the use of the Company’s Lm Technology beyond oncology, specifically to induce an immune response in parasitically infected patients.

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"These patents broaden our protection in HER2 and expand our reach beyond oncology, into parasitically infected patients," said Daniel J. O’Connor, President and Chief Executive Officer of Advaxis. "We are continuing to work diligently on our patent portfolio, currently with 90 granted patents and 111 pending applications, worldwide."

Advaxis is the exclusive licensee of both of these patents. European Patent No. 1804831 will expire on September 14, 2025 and U.S. Patent 9,226,958 will expire on October 3, 2031. The company has an extensive patent portfolio that protects its product candidates and Listeria monocytogenes (Lm) based immunotherapy technology. The Company currently owns or has rights to more than 200 patents and applications globally, which are owned, licensed from, or co-owned with the Trustees of the University of Pennsylvania, Merck, Sharpe & Dohme BV, the National Institutes of Health, the University of Georgia Research Foundation, Inc., and Georgia Regents University. Its patents currently extend protection through 2032.

About HER2 Expressing Solid Tumor Cancers

Human epidermal growth factor receptor 2 (HER2) is overexpressed in a percentage of solid tumors such as breast, gastric, bladder, brain, pancreatic, ovarian and pediatric bone cancer (osteosarcoma). The American Cancer Society estimates that in 2015 in the United States alone there will be 231,840 new cases of invasive breast cancer; 24,590 new cases of gastric cancer; 74,000 new cases of bladder cancer; 22,850 new cases of brain/spinal cancer; 48,960 new cases of pancreatic cancer; 21,290 new cases of ovarian cancer; and 207 new cases of pediatric osteosarcoma. HER2 expression is associated with more aggressive disease, increased risk of relapse and decreased overall survival, and is an important target for immunotherapy.

About ADXS-HER2

ADXS-HER2 is an Lm Technology immunotherapy product candidate being developed by Advaxis to target HER2 expressing cancers. ADXS-HER2 has received orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of osteosarcoma. Advaxis is developing ADXS-HER2 for both human and animal health, and has seen encouraging data in canine osteosarcoma, which is considered a model for human osteosarcoma. Advaxis has licensed ADXS-HER2 and three other immunotherapy constructs to Aratana Therapeutics, Inc. for the development of pet therapeutics.

On January 18, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental New Drug Application (sNDA) submitted by its U.S. subsidiary Eisai Inc. for Eisai’s in-house developed novel anticancer agent lenvatinib mesylate (generic name, "lenvatinib") for use in the treatment of advanced or metastatic renal cell carcinoma, and granted the sNDA Priority Review status (Press release, Eisai, JAN 18, 2016, View Source [SID:1234508800]).

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The FDA’s Priority Review designation is assigned to applications for drugs that would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. Through this process, the FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date (proposed review deadline) of May 16, 2016, 6 months after the sNDA was submitted. Furthermore, lenvatinib has received a Breakthrough Therapy designation from the FDA. In addition, an application seeking approval for use in the treatment of renal cell carcinoma was submitted in Europe in January 2016, and Eisai intends to discuss further steps regarding submission strategies for this potential indication with the regulatory authorities in Japan as well.

This sNDA was based on a Phase II clinical study (Study 205)1 that compared the safety and efficacy among three groups including a combination of lenvatinib (18 mg) plus everolimus (5 mg), lenvatinib alone (24 mg) and everolimus alone (10 mg) in unresectable advanced or metastatic renal cell carcinoma following one prior vascular endothelial growth factor-targeted therapy. From the results of the study, the group who received the combination of lenvatinib plus everolimus demonstrated a significant extension in progression free survival (PFS), the study’s primary endpoint, compared to the everolimus alone group. Additionally, the lenvatinib alone group demonstrated an extension in PFS compared to the everolimus alone group. Both the lenvatinib plus everolimus group and the lenvatinib alone group showed an improvement in objective response rate compared to the everolimus alone group. The most common treatment-emergent adverse events (TEAEs) reported in the lenvatinib plus everolimus group were diarrhea, decreased appetite and fatigue. The most common TEAEs of Grade 3 or higher were diarrhea, hypertension and fatigue.

The number of patients with kidney cancer in the United States is estimated to be approximately 58,000,2 and renal cell carcinoma comprises more than 90% of all malignancies of the kidney.3 For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment is molecular targeted drug therapy, however with low 5-year survival rates, this remains a disease with significant unmet medical need.

Currently lenvatinib has been launched under the brand name Lenvima in the United States, Japan and Europe for use in the treatment of refractory thyroid cancer*. Eisai is committed to exploring the potential clinical benefits of lenvatinib in order to further contribute to patients with cancer and their families.

< Notes to editors >

1. About lenvatinib mesylate (generic name, "lenvatinib")
Lenvatinib is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor proliferation.
Currently, Eisai has obtained approval for lenvatinib in the United States, Japan, Europe, Korea and Canada as a treatment for refractory thyroid cancer, and is undergoing regulatory review throughout the world including in Asia, Russia, Australia, Brazil and Mexico. More specifically, Eisai has obtained approval for the agent indicated in the United States for treatment for locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer, in Japan for the treatment of unresectable thyroid cancer, and in Europe for the treatment of adult patients with progressive, locally advanced or metastatic differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine, respectively. Meanwhile, Eisai is conducting a global Phase III study of lenvatinib in hepatocellular carcinoma as well as Phase II studies of lenvatinib in several other tumor types such as endometrial carcinoma and biliary tract cancer.

2. About the Phase II Clinical Study (Study 205)1
Study 205 was a multicenter, randomized, open-label study of the combination of lenvatinib (18 mg) plus everolimus (5 mg), lenvatinib alone (24 mg), and everolimus alone (10 mg) in patients with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted therapy, and was conducted in Europe and the United States. 153 patients were randomized in a 1:1:1 ratio to one of three treatment arms to compare the efficacy and safety of these three regimens.
From the results of the study, the combination of lenvatinib plus everolimus group demonstrated a significant extension in the study’s primary endpoint of progression free survival (PFS) compared to the everolimus alone group (median PFS for the lenvatinib plus everolimus group: 14.6 months vs median PFS for the everolimus alone group: 5.5 months; Hazard Ratio (HR) 0.40 [95% CI: 0.24-0.68], p=0.0005). Additionally, median PFS for the lenvatinib alone group was 7.4 months, demonstrating an extension in PFS compared to the everolimus alone group (HR: 0.61 [95% CI: 0.38-0.98]).
The study also assessed objective response rate (ORR) and overall survival (OS) as secondary endpoints. Regarding ORR, both the lenvatinib plus everolimus group and the lenvatinib alone group showed an improvement in ORR compared to the everolimus alone group (lenvatinib plus everolimus: 43%, lenvatinib alone: 27%, everolimus alone: 6%). Furthermore, regarding OS, an updated analysis carried out in December 2014 suggested that lenvatinib plus everolimus extends OS compared to everolimus alone (HR 0.51 [95% CI=0.30-0.88]).
The most common treatment-emergent adverse events (TEAEs) reported in the lenvatinib plus everolimus group were diarrhea, decreased appetite and fatigue. The most common TEAEs of Grade 3 or higher (Common Terminology Criteria for Adverse Events) were diarrhea, hypertension and fatigue.

3. About Renal Cell Carcinoma
The number of patients with renal cancer was estimated to be approximately 338,000 worldwide, including approximately 58,000 in the United States, 115,000 in Europe and 17,000 in Japan.2 Renal cell carcinoma comprises more than 90% of all malignancies of the kidney,3 and occurs when malignant cells are found in the lining of the tubules of the kidney. The incidence of renal cell carcinoma in people aged in their late 50s is rising, and is more likely to affect men than women. For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment method is molecular targeted drug therapy, however with low 5-year survival rates, this remains a disease with significant unmet medical need.