On January 4, 2016 Exelixis, Inc. (NASDAQ:EXEL) reported the presentation of positive data from subgroup analyses of METEOR, the phase 3 pivotal trial comparing cabozantinib to everolimus in 658 patients with renal cell carcinoma (RCC) who have experienced disease progression following treatment with a VEGF receptor tyrosine kinase inhibitor (TKI) (Press release, Exelixis, JAN 4, 2016, View Source;p=RssLanding&cat=news&id=2126057 [SID:1234508661]). Cabozantinib treatment resulted in benefits in progression-free survival (PFS), the trial’s primary endpoint, and objective response rate (ORR), a secondary endpoint, across various prespecified and post-hoc analysis subgroups. Importantly, observed benefits were independent of the location and number of organ metastases, tumor burden, the type, duration and number of prior VEGF receptor TKI therapies, and prior PD-1/PD-L1 therapy.

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Bernard Escudier, M.D., chair of the Genitourinary Oncology Committee at the Institut Gustave Roussy (Villejuif, France) and an investigator on the METEOR trial, summarized the results during a press briefing in advance of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Genitourinary Cancers Symposium (ASCO GU), which is being held January 7-9, 2016 in San Francisco. Dr. Escudier will formally present the data (Abstract #499) at ASCO (Free ASCO Whitepaper) GU during an oral presentation session starting at 2:45 p.m. PT on Saturday, January 9, 2016.

"In the METEOR trial, cabozantinib was previously associated with statistically significant improvements in progression-free survival and objective response rate as compared to everolimus, a standard of care in the second-line renal cell carcinoma treatment setting," said Dr. Escudier. "This latest data set demonstrates that these benefits are favorable across a variety of prespecified and post-hoc subgroups, including patients who have received prior therapy with immune checkpoint inhibitors. In addition, cabozantinib was active in patients with low and high tumor burden, including patients with both bone and visceral metastases. Collectively, the data from METEOR suggest that cabozantinib could become an important addition to the renal cell carcinoma treatment landscape if approved."

As previously announced, the METEOR trial met its primary endpoint of demonstrating a statistically significant increase in PFS for cabozantinib as compared to everolimus, as determined by an independent radiology committee. Per the trial protocol, the primary analysis was conducted among the first 375 patients randomized to ensure sufficient follow up and a PFS profile that would not be primarily weighted toward early events. The median PFS for this population was 7.4 months for the cabozantinib arm versus 3.8 months for the everolimus arm, corresponding to a 42% reduction in the rate of disease progression or death for cabozantinib as compared to everolimus (hazard ratio [HR]=0.58, 95% confidence interval [CI] 0.45-0.75, p<0.001). These data were later presented at the European Cancer Congress (ECC) in September 2015 and concurrently published in The New England Journal of Medicine.

The ASCO (Free ASCO Whitepaper) GU presentation will be the first to include PFS data from the METEOR trial’s entire 658-patient study population. As assessed by independent radiology committee, the median PFS across all enrolled patients was 7.4 months for the cabozantinib arm versus 3.9 months for the everolimus arm, corresponding to a 48% reduction in the rate of disease progression or death for cabozantinib as compared to everolimus (HR = 0.52, 95% CI 0.43-0.64, p<0.001).

Updated ORR results from the full 658-patient study population will also be presented at ASCO (Free ASCO Whitepaper) GU for the first time. As assessed by independent radiology committee, the ORR across all 658 patients was 17% for cabozantinib and 3% for everolimus. The median duration of response for cabozantinib was not reached (95% CI 7.2 months; not reached), as compared to 7.4 months (95% CI 1.9 months; not reached) for everolimus. As previously reported at the ECC in September 2015, the ORR for the first 375 patients enrolled was 21% for cabozantinib and 5% for everolimus.

Cabozantinib’s effects on PFS and ORR were favorable across patient subgroups including: ECOG performance status; commonly applied RCC risk criteria developed by Motzer et al.; organ involvement, including bone and overall tumor burden; extent and type of prior VEGF receptor TKI therapy; and prior PD-1/PD-L1 therapy. For patients without prior PD-1/PD-L1 therapy, median PFS was 7.4 months for cabozantinib and 3.9 months for everolimus (HR = 0.54, 95% CI 0.44-0.66). For patients who had received prior PD-1/PD-L1 therapy, the median PFS for cabozantinib was not reached, and the median PFS for everolimus was 4.1 months (HR = 0.22, 95% CI 0.07-0.65).

"These new METEOR subgroup analyses further underscore the potential for cabozantinib to significantly impact the treatment of renal cell carcinoma, an aggressive cancer for which patients and physicians need new options," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "These data were included in our New Drug Application with the U.S. Food and Drug Administration, filed last month, and we intend to include them in our upcoming European Union Marketing Authorization Application, which we expect to submit shortly. Additionally, in 2016 we await the final analysis for METEOR’s overall survival secondary endpoint."

As previously reported, data pertaining to overall survival (OS) in the entire study population of 658 patients, a secondary endpoint of the trial, were immature at the data cutoff. A pre-specified interim analysis triggered by the primary analysis for PFS showed a strong trend in OS favoring cabozantinib (HR=0.67, 95% CI 0.51-0.89, p=0.005). At the time of the interim analysis, the p-value of 0.0019 to achieve statistical significance was not reached, and the trial will continue to the final analysis of OS anticipated in 2016.

Safety data from the trial were consistent with what was previously presented and published.

Cabozantinib is currently marketed in capsule form under the brand name COMETRIQ in the United States for the treatment of progressive, metastatic medullary thyroid cancer (MTC), and in the European Union for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC. COMETRIQ is not indicated for patients with RCC. In the METEOR trial, and all other cancer trials currently underway, Exelixis is investigating a tablet formulation of cabozantinib distinct from the COMETRIQ capsule form. The tablet formulation of cabozantinib is the subject of Exelixis’ New Drug Application with the U.S. Food and Drug Administration for advanced RCC.

About Advanced Renal Cell Carcinoma

The American Cancer Society’s 2015 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common type of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; however, the five-year survival rate for patients with advanced or late-stage metastatic RCC is under 10 percent, with no identified cure for the disease.3

Until the introduction of targeted therapies into the RCC setting a decade ago, treatments for metastatic RCC had historically been limited to cytokine therapy (e.g., interleukin-2 and interferon). In the second and later-line settings, which encompass approximately 17,000 drug-eligible patients in the U.S. and 37,000 globally,4 two small-molecule therapies and an immune checkpoint inhibitor have been approved for the treatment of patients with advanced RCC who have received prior systemic therapy. The currently approved small-molecule agents have shown little differentiation in terms of efficacy and have demonstrated only modest progression-free survival benefit in patients refractory to sunitinib, a commonly-used first-line therapy.

The majority of clear cell RCC tumors exhibit down-regulation of von Hippel-Lindau (VHL) protein function, either due to gene inactivation or epigenetic silencing, resulting in a stabilization of the hypoxia-inducible transcription factors (HIFs) and consequent up-regulation of VEGF, MET and AXL.5 The up-regulation of VEGF may contribute to the angiogenic nature of clear cell RCC, and expression of MET or AXL may be associated with tumor cell viability, a more invasive tumor phenotype and reduced overall survival. 6 Up-regulation of MET and AXL in clear cell RCC has also been shown to occur in response to treatment with VEGF receptor TKIs in preclinical models, indicating a potential role for MET and AXL in the development of resistance to these therapies.7

About Cabozantinib

Cabozantinib inhibits the activity of tyrosine kinases including MET, VEGF receptors, AXL and RET. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and maintenance of the tumor microenvironment.

Cabozantinib, marketed under the brand name COMETRIQ, is currently approved by the U.S. Food and Drug Administration for the treatment of progressive, metastatic medullary thyroid cancer (MTC).

The European Commission granted COMETRIQ conditional approval for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC. Similar to another drug approved in this setting, the approved indication states that for patients in whom Rearranged during Transfection (RET) mutation status is not known or is negative, a possible lower benefit should be taken into account before individual treatment decisions.

Important Safety Information, including Boxed WARNINGS

WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE

Serious and sometimes fatal gastrointestinal perforations and fistulas occur in COMETRIQ-treated patients.
Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated patients.
COMETRIQ treatment results in an increase in thrombotic events, such as heart attacks.
Wound complications have been reported with COMETRIQ.
COMETRIQ treatment results in an increase in hypertension.
Osteonecrosis of the jaw has been observed in COMETRIQ-treated patients.
Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurs in patients treated with COMETRIQ.
The kidneys can be adversely affected by COMETRIQ. Proteinuria and nephrotic syndrome have been reported in patients receiving COMETRIQ.
Reversible Posterior Leukoencephalopathy Syndrome has been observed with COMETRIQ.
Avoid administration of COMETRIQ with agents that are strong CYP3A4 inducers or inhibitors.
COMETRIQ is not recommended for use in patients with moderate or severe hepatic impairment.
COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions (≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation. The most common laboratory abnormalities (≥25%) are increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

Please see full U.S. prescribing information, including Boxed WARNINGS, at www.COMETRIQ.com/downloads/Cometriq_Full_Prescribing_Information.pdf

Please refer to the full European Summary of Product Characteristics for full European Union prescribing information, including contraindication, special warnings and precautions for use at www.sobi.com once posted.

On January 4, 2016 Theragenics Corporation, a medical device company serving the cancer treatment and surgical product markets, reported it has acquired the U.S. and Canadian seed business of Eckert & Ziegler BEBIG, s.a. ("EZB") (Press release, Theragenics, JAN 4, 2016, View Source [SID:1234508659]). This transaction, which was announced on November 30, 2015, closed on December 31, 2015. Financial terms were not disclosed.

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Theragenics has acquired, among other things, the U.S. and Canadian customers of EZB, the U.S. and Canadian rights to the AnchorSeed, VariStrand and related seed products, and the rights to the SeedLock Needle product. These products will be added to Theragenics’ existing product portfolio. Theragenics will manufacture the products at its current facilities in Buford, Georgia.

"This transaction continues our long-standing commitment to prostate brachytherapy and the physicians and patients who depend on it," stated Frank J. Tarallo, Chief Executive Officer of Theragenics Corporation. "As a leading manufacturer and supplier in this market, our focus has always been on quality and service. Theragenics has a long history of providing physicians with the tools necessary to achieve outstanding results for their patients. We welcome the EZB customers and look forward to working with their programs."

Dr. Edgar Löffler, Managing Director of EZB, stated, "Theragenics has been recognized as a leader in prostate brachytherapy and has been a valued partner of EZB in the United States. I am confident that Theragenics will continue the outstanding quality and service to which the EZB customers and patients they serve have grown accustomed."

Mr. Tarallo concluded, "This transaction enhances our capabilities and expands our product portfolio for brachytherapy. Our legacy is improving lives and curing cancer. This transaction enhances our mission.

On January 04, 2016 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for vosaroxin as a treatment for relapsed refractory acute myeloid leukemia (AML) in patients aged 60 years and older (Press release, Sunesis, JAN 4, 2016, View Source;p=RssLanding&cat=news&id=2125727 [SID:1234508658]). Validation confirms that the submission is complete and initiates the Centralized Review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP). Under Centralized Review, the CHMP review period is 210 days, excluding question or opinion response periods, after which the CHMP opinion is reviewed by the European Commission, which usually issues a final decision on EU approval within three months. The MAA submission will be reviewed in the Centralized Procedure, which if authorized, provides a marketing license valid in all 28 EU member states.

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"Validation of our vosaroxin MAA begins the EMA review process and brings us another step closer to delivering a new treatment option to patients with relapsed refractory AML," said Deborah Thomas, Ph.D., Vice President, Regulatory Affairs and Medical Writing. "Following encouraging interactions with the agency last summer, we look forward to progressing to the next stage of the review process, which includes the 120-day questions following the assessment report by the CHMP."

"We believe European marketing authorization would represent a significant opportunity both commercially and in providing regulatory validation for other geographies around the world," said Daniel Swisher, Chief Executive Officer of Sunesis. "We look forward to providing more updates in 2016 as we move forward with this regulatory process."

About QINPREZO (vosaroxin)
QINPREZO (vosaroxin) is an anti-cancer quinolone derivative (AQD), a class of compounds that has not been used previously for the treatment of cancer. Preclinical data demonstrate that vosaroxin both intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest and apoptosis. Both the U.S. Food and Drug Administration (FDA) and European Commission have granted orphan drug designation to vosaroxin for the treatment of AML. Additionally, vosaroxin has been granted fast track designation by the FDA for the potential treatment of relapsed or refractory AML in combination with cytarabine. Vosaroxin is an investigational drug that has not been approved for use in any jurisdiction.

The trademark name QINPREZO is conditionally accepted by the FDA and the EMA as the proprietary name for the vosaroxin drug product candidate.

About AML
AML is a rapidly progressing cancer of the blood characterized by the uncontrolled proliferation of immature blast cells in the bone marrow. It is estimated that the prevalence of AML across major global markets (U.S., France, Germany, Italy, Spain, United Kingdom and Japan) is over 75,000. AML is generally a disease of older adults, and the median age of a patient diagnosed with AML is about 67 years. AML patients with relapsed or refractory disease and newly diagnosed AML patients over 60 years of age with poor prognostic risk factors typically die within one year, resulting in an acute need for new treatment options for these patients.