Lilly Cancer Treatment Clears FDA Hurdle

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The U.S. Food and Drug Administration has approved a stomach cancer treatment combination with a drug from Indianapolis-based Eli Lilly and Co. (NYSE: LLY). The company says the announcement follows a previous FDA approval to use Cyramza as a single agent. November 5, 2014

News Release

INDIANAPOLIS, Ind. -- Eli Lilly and Company (NYSE: LLY) announced today that the U.S. Food and Drug Administration (FDA) has approved CYRAMZA (ramucirumab) in combination with paclitaxel (a type of chemotherapy) as a treatment for people with advanced or metastatic gastric (stomach) or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy. CYRAMZA now has two FDA approvals for these patients. Today's announcement follows the April approval of CYRAMZA as a single agent - the first approval of a treatment in the U.S. for patients in this setting.

"This FDA approval of CYRAMZA represents another milestone for people battling this devastating and difficult-to-treat disease," said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. "Lilly is pleased to continue delivering on its commitment to provide new treatment options to people living with cancer and those who care for them."

Stomach cancer is the fifth most common cancer in the world and is the third-leading cause of cancer death.i In the U.S., approximately 22,000 people will be diagnosed with stomach cancer in 2014. CYRAMZA (ramucirumab injection 10 mg/mL solution) is the only FDA-approved second-line treatment option for patients with advanced or metastatic gastric or GEJ adenocarcinoma whose disease has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy.

This FDA approval for CYRAMZA is based on the Phase III RAINBOW trial, which compared CYRAMZA plus paclitaxel to placebo plus paclitaxel. Efficacy endpoints in the trial included the major efficacy outcome measure of overall survival and the supportive efficacy outcome measures of progression-free survival and objective response rate. The labeling for CYRAMZA contains a Boxed Warning regarding increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. CYRAMZA should be permanently discontinued in patients who experience severe bleeding. See the Important Safety Information at the end of this press release and the Prescribing Information.

CYRAMZA has been granted Orphan Drug Designation by the FDA for this indication. Orphan drug status is given in the U.S. by the FDA's Office of Orphan Products Development (OOPD) to medicines that show promise for the treatment of rare diseases.

Lilly is committed to offering patient assistance programs for eligible patients receiving CYRAMZA treatment. Patients, physicians, pharmacists or other healthcare professionals with additional questions about CYRAMZA should contact The Lilly Answers Center at 1-800-LillyRx (1-800-545-5979) or visit www.lilly.com. Healthcare professionals may also find additional product information on CYRAMZA at www.CYRAMZA.com.

About CYRAMZA (ramucirumab)

CYRAMZA as a single agent, or in combination with paclitaxel (a type of chemotherapy), is approved for the treatment of people with advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy.

CYRAMZA is an antiangiogenic therapy. It is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that specifically binds and blocks activation of VEGF Receptor 2, by blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. CYRAMZA inhibited angiogenesis in an in vivo animal model.

About Angiogenesis

Angiogenesis is the process of making new blood vessels. In a person with cancer, angiogenesis creates new blood vessels that give a tumor its own blood supply, allowing it to grow and spread.

Some tumors create proteins called VEGF. These proteins attach to the VEGF receptors of blood vessel cells causing new blood vessels to form around the tumors, enabling growth. Blocking the VEGF protein from linking to the blood vessels helps to inhibit tumor growth by slowing angiogenesis and the blood supply that feeds tumors. Of the three known VEGF receptors, VEGF Receptor 2 is linked most closely to VEGF-induced tumor angiogenesis.

About RAINBOW

RAINBOW was a multinational, randomized, double-blinded, placebo-controlled Phase III study of CYRAMZA plus paclitaxel compared to placebo plus paclitaxel in people with locally advanced or metastatic gastric or GEJ adenocarcinoma, whose cancer had progressed after fluoropyrimidine- and platinum-containing chemotherapy. Initiated in 2010, the global study randomized a total of 665 patients across 27 countries in North America, South America, Europe, Australia and Asia. RAINBOW is the first Phase III study to demonstrate a survival benefit with a biologic used in combination with chemotherapy in this setting.

CYRAMZA plus paclitaxel significantly extended median overall survival compared with placebo plus paclitaxel (9.6 months [95% confidence interval (CI): 8.5, 10.8] vs. 7.4 months [95% CI: 6.3, 8.4], respectively; hazard ratio 0.81 [95% CI: 0.68, 0.96]; P=0.017). Furthermore, CYRAMZA plus paclitaxel significantly delayed disease progression (progression-free survival of 4.4 months for CYRAMZA plus paclitaxel [95% CI: 4.2, 5.3]) vs. 2.9 months for placebo plus paclitaxel [95% CI: 2.8, 3.0]; hazard ratio 0.64 [95% CI: 0.54, 0.75]; P < 0.001).="" significantly="" more="" patients="" responded="" to="" cyramza="" combined="" with="" paclitaxel="" than="" with="" paclitaxel="" alone="" (28%="" [95%="" ci:="" 23,="" 33]="" for="" cyramza="" plus="" paclitaxel="" vs.="" 16%="" [95%="" ci:="" 13,="" 20]="" for="" placebo="" plus="" paclitaxel;="" p="">< 0.001).="" the="" percentage="" of="" deaths="" at="" the="" time="" of="" analysis="" was="" 78%="" (256="" patients)="" and="" 78%="" (260="" patients)="" in="" the="" cyramza-plus-paclitaxel="" and="" placebo-plus-paclitaxel="" treatment="" arms,="" respectively.="" the="" progression-free="" survival="" number="" of="" events="" was="" 279="" (85%)="" and="" 296="" (88%)="" for="" the="" cyramza-plus-paclitaxel="" and="" placebo-plus-paclitaxel="" treatment="" arms,="">

The labeling for CYRAMZA contains a Boxed Warning for hemorrhage and additional Warnings and Precautions for arterial thromboembolic events, hypertension, infusion-related reactions, gastrointestinal perforations, impaired wound healing, clinical deterioration in patients with Child-Pugh B or C cirrhosis, and reversible posterior leukoencephalopathy syndrome. In the RAINBOW trial, the most common adverse reactions (all grades) observed in patients treated with CYRAMZA plus paclitaxel at a rate of ≥30% and ≥2% higher than placebo plus paclitaxel were fatigue (57% vs. 44%), neutropenia (low white blood cell count) (54% vs. 31%), diarrhea (32% vs. 23%), and epistaxis (bleeding from the nose) (31% vs. 7%). The most common serious adverse events with CYRAMZA plus paclitaxel in the RAINBOW trial were neutropenia (3.7%) and febrile neutropenia (fever and potentially other infection signs along with low white blood cell count) (2.4%); 19% of patients treated with CYRAMZA plus paclitaxel received granulocyte colony-stimulating factors (treatment for low white blood cells). See the Important Safety Information at the end of this press release and the Prescribing Information.

About Gastric Cancer

Gastric (stomach) cancer is a major health problem. It is the fifth most common cancer in the world and is the third-leading cause of cancer death. There were nearly one million new cases worldwide in 2012 (631,000 men, 320,000 women) with approximately 723,000 deaths (469,000 men, 254,000 women).iii Stomach cancer is more prevalent in countries outside the U.S. and EU.iv In the U.S., it is estimated that approximately 22,000 people will be diagnosed with gastric cancer in 2014.v

Gastric cancer is a disease in which cancer cells form