Ipsen is pleased to announce that its partner Exelixis obtained FDA Approval of CABOMETYX™ (cabozantinib) tablets for patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy

On April 25 2016 Ipsen (Euronext: IPN; ADR: IPSEY) reported that its partner Exelixis, Inc. (NASDAQ:EXEL) received approval from the U.S. Food and Drug Administration (FDA) for CABOMETYX (cabozantinib) tablets earlier today for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy (Press release, Ipsen, APR 25, 2016, View Source [SID:1234511439]). On February 29, 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan.

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RCC is the most common form of kidney cancer in adults. The incidence of advanced RCC is estimated to be around 20,000 new patients per year in Ipsen’s territories.

CABOMETYX, which was granted Fast Track and Breakthrough Therapy designations by the FDA, is the first therapy to demonstrate in a large, randomized phase 3 trial for patients with advanced RCC, robust and clinically meaningful improvements in all three key efficacy parameters — overall survival, progression free survival and objective response rate.

Compared with everolimus, CABOMETYX is associated with a 42 percent reduction in the rate of disease progression or death and 34 percent reduction in the rate of death. Median progressionfree survival for CABOMETYX is 7.4 months versus 3.8 months for everolimus (HR=0.58, 95% CI 0.45-0.74, P<0.0001). Median overall survival is 21.4 months for patients receiving CABOMETYX versus 16.5 months for those receiving everolimus (HR=0.66, 95% CI 0.53-0.83, P=0.0003).

In Europe, the Marketing Authorization Application (MAA) for cabozantinib in advanced RCC has been accepted and granted accelerated assessment. With this designation, the MAA is eligible for a 150-day review, versus the standard 210 days (excluding clock stops when information is requested by the EMA).

Exelixis press release is available here: http://bit.ly/24gckfO

Pipeline-Ocrelizumab

Ocrelizumab is a humanized monoclonal antibody that selectively targets the CD20-positive B-cells implicated in the inflammatory and neurodegenerative processes of multiple sclerosis (MS), to effectively impact disease progression while maintaining immunosurveillance (Company Pipeline, Hoffmann-La Roche , APR 25, 2016, View Source [SID:1234511389]).

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Phase III TAILOR Landmark Study Demonstrates Significant Benefits of Erbitux in Combination with FOLFOX Over FOLFOX Alone

On April 25, 2016 Merck, a leading science and technology company, reported that the pivotal Chinese Phase III TAILOR study met its primary endpoint of significantly increasing progression-free survival (PFS) in patients with RAS wild-type metastatic colorectal cancer (mCRC) treated with Erbitux (cetuximab) plus FOLFOX chemotherapy, compared with FOLFOX alone (Press release, Merck & Co, APR 25, 2016, View Source;newsType=1 [SID:1234511390]).

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"We are thrilled with the TAILOR results that bring a major contribution to the available scientific evidence of Erbitux’s efficacy in combination with FOLFOX as a standard first-line treatment for patients with RAS wild-type metastatic colorectal cancer. This marks a significant step in the execution of our strategy in oncology, notably the expansion in growth markets like China," said Luciano Rossetti, Head of Global Research and Development of Merck’s biopharma business. "These impressive results reinforce the value and imperative of RAS biomarker testing in clinical practice, so as to provide patients with the right targeted therapy. These results also underscore why we continue to devote our efforts towards both improving testing and ensuring access to Erbitux worldwide." 1–4

The clinical benefit that Erbitux offers to RAS wild-type mCRC patients is further strengthened by the secondary endpoint results, which support the superiority shown for PFS. The safety profile of Erbitux in the TAILOR clinical trial was manageable and similar to that observed in other pivotal trials, with no unexpected safety findings. The full study results will be submitted to upcoming international scientific meetings.

Both the National Comprehensive Cancer Network (U.S.) and the European Society for Medical Oncology clinical guidelines recommend first-line treatment with Erbitux plus FOLFOX or FOLFIRI for patients with RAS wild-type mCRC.5,6

"We are excited that the TAILOR study is positive and that Erbitux in combination with chemotherapy could become a new first-line treatment option for metastatic colorectal cancer patients in China, once approved," said Professor Shukui Qin from Nanjing Bayi Hospital, China, Coordinating Investigator in the TAILOR study. "It is also reassuring that the results reflect those previously observed, and support the indicated first-line use of Erbitux plus FOLFOX in many countries."

Erbitux has obtained marketing authorization in over 90 countries worldwide. In Europe, Erbitux is indicated as first-line therapy for patients with RAS wild-type mCRC tumors, together with the oxaliplatin-containing regimen FOLFOX in treatment-naïve patients or together with regimens containing irinotecan (e.g. FOLFIRI).7 More than 442,000 patients with mCRC have been treated with Erbitux.

About the TAILOR study
The TAILOR study is a Phase III, open-label, randomized, controlled, multicenter trial designed to compare Erbitux in combination with FOLFOX-4 versus FOLFOX-4 alone in the first-line treatment of Chinese patients with RAS wild-type mCRC. All randomized subjects were planned to receive treatment until the occurrence of progressive disease (PD) or unacceptable toxicity. The study enrolled 397 patients with RAS wild-type mCRC. The primary endpoint of the trial is progression-free survival. Secondary endpoints include: overall survival, best overall response rate, time to treatment failure and rate of curative surgery for liver metastases.

About mCRC
Approximately half of patients with mCRC have RAS wild-type tumors and half have RAS mutant tumors.8 Results from studies assessing RAS mutation status in patients with mCRC have shown that antiepidermal growth factor receptor (EGFR) monoclonal antibody therapies, such as Erbitux (cetuximab), can improve outcomes in patients with RAS wild-type mCRC.1-4 Colorectal cancer (CRC) is the third most common cancer worldwide, with an estimated incidence of more than 1.36 million new cases annually.9 An estimated 694,000 deaths from CRC occur worldwide every year, accounting for 8.5% of all cancer deaths and making it the fourth most common cause of death from cancer.9 Almost 55% of CRC cases are diagnosed in developed regions of the world, and incidence and mortality rates are substantially higher in men than in women.9

About Erbitux
Erbitux is a highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard nonselective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.
The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.
Erbitux has already obtained market authorization in over 90 countries world-wide for the treatment of colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck (SCCHN). Merck licensed the right to market Erbitux outside the US and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas.

Delay in initiation of adjuvant trastuzumab therapy leads to decreased overall survival and relapse-free survival in patients with HER2-positive non-metastatic breast cancer.

Trastuzumab reduces the risk of relapse in women with HER2-positive non-metastatic breast cancer, but little information exists on the timing of trastuzumab initiation. The study investigated the impact of delaying the initiation of adjuvant trastuzumab therapy for &amp;gt;6 months after the breast cancer diagnosis on time to relapse, overall survival (OS), and relapse-free survival (RFS) among patients with non-metastatic breast cancer. Adult women with non-metastatic breast cancer who initiated trastuzumab adjuvant therapy without receiving any neoadjuvant therapy were selected from the US Department of Defense health claims database from 01/2003 to 12/2012. Two study cohorts were defined based on the time from breast cancer diagnosis to trastuzumab initiation: &amp;gt;6 months and ≤6 months. The impact of delaying trastuzumab initiation on time to relapse, OS, and RFS was estimated using Cox regression models adjusted for potential confounders. Of 2749 women in the study sample, 79.9 % initiated adjuvant trastuzumab within ≤6 months of diagnosis and 20.1 % initiated adjuvant trastuzumab &amp;gt;6 months after diagnosis. After adjusting for confounders, patients who initiated trastuzumab &amp;gt;6 months after the breast cancer diagnosis had a higher risk of relapse, death, or relapse/death than those who initiated trastuzumab within ≤6 months of diagnosis (hazard ratios [95 % CIs]: 1.51 [1.22-1.87], 1.54 [1.12-2.12], and 1.43 [1.16-1.75]; respectively). The results of this population-based study suggest that delays of &amp;gt;6 months in the initiation of trastuzumab among HER2-positive non-metastatic breast cancer patients are associated with a higher risk of relapse and shorter OS and RFS.

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Detection of High-grade Prostate Cancer Using a Urinary Molecular Biomarker-Based Risk Score.

To reduce overdiagnosis and overtreatment, a test is urgently needed to detect clinically significant prostate cancer (PCa).
To develop a multimodal model, incorporating previously identified messenger RNA (mRNA) biomarkers and traditional risk factors that could be used to identify patients with high-grade PCa (Gleason score ≥7) on prostate biopsy.
In two prospective multicenter studies, urine was collected for mRNA profiling after digital rectal examination (DRE) and prior to prostate biopsy. The multimodal risk score was developed on a first cohort (n=519) and subsequently validated clinically in an independent cohort (n=386).
The mRNA levels were measured using reverse transcription quantitative polymerase chain reaction. Logistic regression was used to model patient risk and combine risk factors. Models were compared using the area under the curve (AUC) of the receiver operating characteristic, and clinical utility was evaluated with a decision curve analysis (DCA).
HOXC6 and DLX1 mRNA levels were shown to be good predictors for the detection of high-grade PCa. The multimodal approach reached an overall AUC of 0.90 (95% confidence interval [CI], 0.85-0.95) in the validation cohort (AUC 0.86 in the training cohort), with the mRNA signature, prostate-specific antigen (PSA) density, and previous cancer-negative prostate biopsies as the strongest, most significant components, in addition to nonsignificant model contributions of PSA, age, and family history. For another model, which included DRE as an additional risk factor, an AUC of 0.86 (95% CI, 0.80-0.92) was obtained (AUC 0.90 in the training cohort). Both models were successfully validated, with no significant change in AUC in the validation cohort, and DCA indicated a strong net benefit and the best reduction in unnecessary biopsies compared with other clinical decision-making tools, such as the Prostate Cancer Prevention Trial risk calculator and the PCA3 assay.
The risk score based on the mRNA liquid biopsy assay combined with traditional clinical risk factors identified men at risk of harboring high-grade PCa and resulted in a better patient risk stratification compared with current methods in clinical practice. Therefore, the risk score could reduce the number of unnecessary prostate biopsies.
This study evaluated a novel urine-based assay that could be used as a noninvasive diagnostic aid for high-grade prostate cancer (PCa). When results of this assay are combined with traditional clinical risk factors, risk stratification for high-grade PCa and biopsy decision making are improved.
Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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