Exelixis, Inc. and Ipsen today announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA) provided a positive opinion for Cabometyx™ (cabozantinib) 20, 40, 60mg for the treatment of advanced renal cell carcinoma (RCC) in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy and recommended it for marketing authorization. The CHMP positive opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU).

David Meek, Chief Executive Officer of Ipsen, said: “We are pleased that European patients with renal cell cancer may soon have access to Cabometyx™. Ipsen is very proud to receive this positive CHMP opinion for Cabometyx™, a new drug with unprecedented clinical results in the treatment of advanced renal cell carcinoma. Cabometyx™ has demonstrated robust and consistent benefits regardless of prior treatment, location and extent of tumor metastases in previously treated patients suffering from advanced renal cell carcinoma.” 

“The positive CHMP opinion for Cabometyx™ is a significant milestone for both Exelixis and Ipsen as we work together to bring this important treatment option to patients with advanced renal cell carcinoma,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. “With our shared mission of delivering innovative therapies to improve the treatment of cancer, we have the opportunity to change the way this patient population is treated. If approved by the European Commission, Cabometyx™ will provide a new treatment option with proven clinically significant benefit across all three efficacy endpoints addressing a serious unmet medical need.”

The positive CHMP opinion was adopted following an accelerated review procedure reserved for medicinal products expected to be of major public health interest. The recommendation will now be reviewed by the European Commission, which has the authority to approve medicines for use in the 28 countries of the European Union, Norway and Iceland, with a decision expected two months post CHMP opinion.

The detailed recommendations for the use of this product will be described in the Summary of Product Characteristics (SmPC), to be made available if the medication receives marketing authorization from the European Commission.

On January 28, 2016, the European Medicines Agency (EMA) validated Exelixis’ Marketing Authorization Application (MAA) for Cabometyx™ (cabozantinib) as a treatment for patients with advanced renal cell carcinoma who have received one prior therapy. The MAA has been granted accelerated assessment, making it eligible for a 150-day review, versus the standard 210 days. 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.

On April 25, 2016 Cabometyx™ (cabozantinib) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy.

About the METEOR Phase 3 Pivotal Trial

METEOR was an open-label, event-driven trial of 658 patients with advanced renal cell carcinoma who had failed at least one prior VEGFR TKI therapy. The primary endpoint was PFS in the first 375 patients treated. Secondary endpoints included OS and objective response rate in all enrolled patients. The trial was conducted at approximately 200 sites in 26 countries, and enrollment was weighted toward Western Europe, North America, and Australia. Patients were randomized 1:1 to receive 60 mg of Cabometyx™ (cabozantinib) daily or 10 mg of everolimus daily and were stratified based on the number of prior VEGFR TKI therapies received and on MSKCC risk criteria. No cross-over was allowed between the study arms.

METEOR met its primary endpoint of significantly improving PFS. Compared with everolimus, Cabometyx™ (cabozantinib) was associated with a 42 percent reduction in the rate of disease progression or death. Median PFS for Cabometyx™ (cabozantinib) was 7.4 months versus 3.8 3 / 7 months for everolimus (HR=0.58, 95% CI 0.45-0.74, P<0.0001). Cabometyx™ (cabozantinib) also significantly improved the objective response rate compared with everolimus (p<0.0001). These data were presented at the European Cancer Congress in September 2015 and published in The New England Journal of Medicine. ¹

Cabometyx™ (cabozantinib) also demonstrated a statistically significant and clinically meaningful increase in OS in the METEOR trial. Compared with everolimus, Cabometyx™ (cabozantinib) was associated with a 34 percent reduction in the rate of death. Median OS was 21.4 months for patients receiving Cabometyx™ (cabozantinib) versus 16.5 months for those receiving everolimus (HR=0.66, 95% CI 0.53-0.83, P=0.0003). Cabometyx™ (cabozantinib) benefit in OS was robust and consistent across all pre-specified subgroups. In particular, benefit was observed regardless of risk category, location and extent of tumor metastases, and tumor MET expression level. These results were presented on June 5, 2016 at the ASCO Annual Meeting and concurrently published in The Lancet Oncology. ²

At the time of the analysis, the median duration of treatment in the trial was 8.3 months with Cabometyx™ (cabozantinib) versus 4.4 months with everolimus. The most frequent adverse events regardless of causality were diarrhea, fatigue, decreased appetite and hypertension for Cabometyx™ and fatigue, anemia, decreased appetite and cough for everolimus. Dose reductions occurred for 62 percent and 25 percent of patients, respectively. Discontinuation rate due to an adverse event not related to disease progression was 12 percent with Cabometyx™ (cabozantinib) and 11 percent with everolimus.

About Advanced Renal Cell Carcinoma

Renal cell carcinoma (RCC) represents 2-3% of all cancers³ , with the highest incidence occurring in Western countries. Generally, during the last two decades until recently, there has been an annual increase of about 2% in incidence both worldwide and in Europe, though in Denmark and Sweden a continuing decrease has been observed⁴ . In 2012, there were approximately 84,400 new cases of RCC and 34,700 kidney cancer related deaths within the European Union⁵ . In Europe, overall mortality rates for RCC have increased up until the early 1990s, with rates generally stabilizing or declining thereafter6 . There has been a decrease in mortality since the 1980s in Scandinavian countries and since the early 1990s in France, Germany, Austria, the Netherlands, and Italy. However, in some European countries (Croatia, Estonia, Greece, Ireland, Slovakia), mortality rates still show an upward trend with increasing rates⁶ .

The majority of clear cell RCC tumors have lower than normal levels of a protein called von HippelLindau, which leads to higher levels of MET, AXL and VEGF. ^7,8 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.^9-12 MET and AXL may provide escape pathways that drive resistance to VEGFR inhibitors.^8,9

About CABOMETYX™ (cabozantinib)

Cabometyx™ (cabozantinib) targets include MET, AXL and VEGFR-1, -2 and -3. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.

About Exelixis

Exelixis, Inc. (NASDAQ: EXEL) is a biopharmaceutical company committed to the discovery, development and commercialization of new medicines with the potential to improve care and outcomes for people with cancer. Since its founding in 1994, three medicines discovered at Exelixis have progressed through clinical development to receive regulatory approval. Currently, Exelixis is focused on advancing cabozantinib, an inhibitor of multiple tyrosine kinases including MET, AXL and VEGF receptors, which has shown clinical antitumor activity in more than 20 forms of cancer and is the subject of a broad clinical development program. Two separate formulations of cabozantinib have received regulatory approval to treat certain forms of kidney and thyroid cancer and are marketed for those purposes as CABOMETYX™ tablets (U.S.) and COMETRIQ^® capsules (U.S. and EU), respectively. Another Exelixis-discovered compound, COTELLIC™ (cobimetinib), a selective inhibitor of MEK, has been approved in major territories including the United States and European Union, and is being evaluated for further potential indications by Roche and Genentech (a member of the Roche Group) under a collaboration with Exelixis. For more information on Exelixis, please visit www.exelixis.com or follow @ExelixisInc on Twitter.

Exelixis Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including, without limitation, statements related to: the review by the EC of the CHMP’s positive opinion for CabometyxTM (cabozantinib) 20, 40, 60mg for te treatment of advanced RCC in adults following prior VEGF-targeted therapy; the potential for European patients with RCC to soon have access to CabometyxTM; Exelixis’ shared mission with Ipsen to deliver innovative therapies to improve the treatment of cancer; the opportunity to change the way the RCC patient population is treated the potential for Cabometyx™ to provide a new treatment option with proven clinically significant benefit across all three efficacy endpoints addressing a serious unmet medical need, if approved by the EC; the expectation that the EC will issue a decision on the approval of CabometyxTM in two months; Exelixis’ plan to work with the European Commission to complete the review process for COMETRIQ’s proposed indication as a treatment for progressive, unresectable locally advanced or metastatic MTC; the potential approval by the European Commission of the proposed indication of COMETRIQ for the treatment of progressive, unresectable locally advanced or metastatic MTC;; Exelixis’ commitment to the discovery, development and commercialization of new medicines with the potential to improve care and outcomes for people with cancer; Exelixis’ focus on advancing cabozantinib; and the continued development of cobimetinib. Words such as “will,” “may,” “mission,” “opportunity,” “expected,” “committed,” “potential,” “focused,” or other similar expressions identify forward-looking statements, but the absence of these words does not necessarily mean that a statement is not forward-looking. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: risks and uncertainties related to regulatory review and approval processes and Exelixis’ compliance with applicable legal and regulatory requirements; Exelixis’ dependence on its relationship with Ipsen, including, the level of Ipsen’s investment in the resources necessary to successfully commercialize cabozantinib in the territories where it is approved; the risk that unanticipated developments could adversely affect the commercialization of CABOMETYX; Exelixis’ ability to conduct clinical trials of cabozantinib sufficient to achieve a positive completion; risks related to the potential failure of cabozantinib to demonstrate safety and efficacy in clinical testing; Exelixis’ dependence on its relationship with Genentech/Roche with respect to cobimetinib and Exelixis’ ability to maintain its rights under the collaboration; Exelixis’ ability to protect the company’s intellectual property rights; market competition; changes in economic and business conditions, and other factors discussed under the caption “Risk Factors” in Exelixis’ annual report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 4, 2016, and in Exelixis’ future filings with the SEC. The forward-looking statements made in this press release speak only as of the date of this press release. Exelixis expressly disclaims any duty, obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Exelixis’ expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.

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