Full Press Release Details
INDIANAPOLIS , June 19, 2015 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY ) announced that The Lancet Oncology has published results of the Phase III REACH trial that evaluated CYRAMZA ® (ramucirumab) as a second-line treatment for people with hepatocellular carcinoma (HCC), also known as liver cancer. While the REACH trial's primary endpoint of overall survival favored the CYRAMZA arm, it was not statistically significant. However, encouraging single-agent CYRAMZA activity was observed, with meaningful improvements in key secondary endpoints as well as within certain patient subgroups.
The global, randomized, double-blind REACH trial compared ramucirumab plus best supportive care to placebo plus best supportive care as a second-line treatment in patients with HCC after being treated with sorafenib in the first-line setting. Median overall survival (OS) was 9.2 months on the ramucirumab arm compared to 7.6 months on the placebo arm (HR 0.866; 95% CI: 0.717-1.046; p=0.1391). While the median OS was not statistically significant, a prespecified subgroup of patients with an elevated baseline of alpha-fetoprotein (AFP) ≥400 ng/mL showed a greater survival improvement with ramucirumab treatment. Median OS in this subgroup of patients was 7.8 months in the ramucirumab arm compared to 4.2 months in the placebo arm (HR 0.674; 95% CI 0.508-0.895; p=0.0059).
"Advanced liver cancer carries a poor prognosis with limited treatment options. Several phase III studies to date have not been able to demonstrate improved survival in the second-line setting following sorafenib failure," said Andrew X. Zhu , M.D., director of Liver Cancer Research at Massachusetts General Hospital Cancer Center and principal investigator of the REACH trial. "Further analyses from the REACH study have identified AFP as a potential marker for selecting patients with advanced hepatocellular carcinoma who may benefit from ramucirumab treatment."
The REACH study analyses presented at the Gastrointestinal Cancers Symposium earlier this year concluded that a greater reduction in the risk of death in patients with progressively higher baseline AFP values warrants further investigation. Based on these findings, Lilly will soon begin enrollment in REACH-2 , a new Phase III trial to evaluate the benefit of ramucirumab treatment in advanced liver cancer patients with an elevated baseline AFP (ClinicalTrials.gov identifier: NCT02435433).
"Globally, a high unmet need exists in second-line hepatocellular carcinoma, and currently there are no therapies approved in the U.S., EU or Japan to treat patients in this setting," said Richard Gaynor , M.D., senior vice president, product development and medical affairs for Lilly Oncology. "We are encouraged by the efficacy seen overall in the REACH study, especially in specific subpopulations, and we hope to confirm those results with the new CYRAMZA Phase III trial."
The safety data in the REACH study were consistent with results from previous single-agent ramucirumab studies and the safety information included in the U.S. Prescribing Information for ramucirumab. The most common (≥5% incidence) clinical grade ≥3 adverse events occurring more frequently in patients on the ramucirumab arm compared to the control arm were hypertension (12% vs. 4%), asthenia (fatigue) (5% vs. 2%), and malignant neoplasm progression (6% vs. 4%). The safety profile of ramucirumab in patients with elevated baseline AFP >400 ng/mL was consistent with that observed in the overall safety population.
Ramucirumab has been granted Orphan Drug Designation for treatment of hepatocellular carcinoma in the U.S. and EU. Orphan drug status is given – in the U.S. by the FDA's Office of Orphan Products Development (OOPD) and in the EU by the European Commission – to medicines that have demonstrated promise for the treatment of rare diseases.
About the REACH Trial REACH is a global, randomized, double-blind Phase III study of ramucirumab plus best supportive care compared to placebo plus best supportive care as a second-line treatment in patients with hepatocellular carcinoma who have been previously treated with sorafenib in the first-line setting. Initiated in 2010, the study enrolled 565 patients across 27 countries; as defined in the trial protocol, the primary analyses are focused on patients with a Child-Pugh score of <7 (Child-Pugh Class A only). The primary endpoint (also referred to as the major efficacy outcome measure) of the REACH trial was overall survival and key secondary endpoints (also referred to as the supportive efficacy outcome measures) include: progression-free survival; overall response rate; time to progression; and safety.
About Alpha-Fetoprotein Alpha-fetoprotein (AFP) is a glycoprotein that is produced in early fetal life by the liver and by a variety of tumors including hepatocellular carcinoma (HCC), hepatoblastoma, and nonseminomatous germ cell tumors of the ovary and testis. Most studies report elevated AFP concentrations in approximately 70 percent of patients with HCC and the test is commonly used in the management of HCC. i 400 ng/mL is a commonly-used, established threshold for diagnostic and prognostic purposes, as well as for selection of patients for transplantation.
About Hepatocellular Carcinoma Liver cancer is the sixth most common cancer worldwide and the second-leading cause of cancer-related death. Each year approximately 780,000 new cases of liver cancer are diagnosed worldwide, and more than 740,000 will die of the disease. ii According to the World Health Organization, approximately 30,000 people are diagnosed with liver cancer, and 24,000 will die from the disease each year in the United States. In Europe and Japan , an estimated 63,000 and 36,000 people are diagnosed with liver cancer, and 62,000 and 33,000 will die, respectively. ii More than 80 percent of primary carcinomas of the liver are hepatocellular carcinomas (HCC) or hepatomas. iii
In general, most patients with advanced HCC have liver damage and have limited treatment options. Once they have developed advanced disease, surgery is not an option for the majority of advanced HCC patients, as the tumor has often grown or metastasized to the extent that resection is not feasible. Specifically, once patients enter the second-line setting, there are no approved therapies and supportive care is the standard in this patient population. Overall, the prognosis for advanced HCC patients is typically very poor.
About CYRAMZA ® (ramucirumab) In the U.S., CYRAMZA (ramucirumab) is approved for use as a single agent or 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. It is also approved in combination with docetaxel (a type of chemotherapy) as a treatment for people with metastatic non-small cell lung cancer (NSCLC) whose cancer has progressed on or after platinum-based chemotherapy. Additionally, it is approved with FOLFIRI (a type of chemotherapy) as a treatment for people with metastatic colorectal cancer (mCRC) whose cancer has progressed on or after therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.
There are several additional studies underway or planned to investigate CYRAMZA as a single agent and in combination with other anti-cancer therapies for the treatment of multiple tumor types.
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 and VEGF 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 and 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.
INDICATIONS Gastric Cancer CYRAMZA, as a single agent or in combination with paclitaxel, is indicated for the treatment of patients with advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
Non-Small Cell Lung Cancer CYRAMZA, in combination with docetaxel, is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving CYRAMZA.
Colorectal Cancer CYRAMZA, in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.
IMPORTANT SAFETY INFORMATION FOR CYRAMZA
| WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, AND IMPAIRED WOUND HEALING |
| Hemorrhage: CYRAMZA increased the risk of hemorrhage and gastrointestinal hemorrhage, including severe and sometimes fatal hemorrhagic events. Permanently discontinue CYRAMZA in patients who experience severe bleeding. |
| Gastrointestinal Perforation: CYRAMZA can increase the risk of gastrointestinal perforation, a potentially fatal event. Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation. |
| Impaired Wound Healing: Impaired wound healing can occur with antibodies inhibiting the VEGF pathway. Discontinue CYRAMZA therapy in patients with impaired wound healing. Withhold CYRAMZA prior to surgery and discontinue CYRAMZA if a patient develops wound healing complications. |
Warnings and Precautions
Arterial Thromboembolic Events (ATEs)
Infusion-Related Reactions (IRRs)
Gastrointestinal Perforations
Impaired Wound Healing
Clinical Deterioration in Child-Pugh B or C Cirrhosis
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
Proteinuria Including Nephrotic Syndrome
Thyroid Dysfunction
Embryofetal Toxicity
Most Common Adverse Reactions—Single Agent
Most Common Adverse Reactions—Combination With Paclitaxel
Most Common Adverse Reactions—Combination With Docetaxel
Most Common Adverse Reactions—Combination With FOLFIRI
Drug Interactions
Use in Specific Populations
Please see full Prescribing Information for CYRAMZA, including Boxed Warnings for hemorrhage, gastrointestinal perforation, and impaired wound healing. RB-P HCP ISI 24APR2015
About Lilly Oncology For more than fifty years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. To learn more about Lilly's commitment to people with cancer, please visit www.LillyOncology.com .
About Eli Lilly and Company Lilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at www.lilly.com and newsroom.lilly.com/social-channels . (P-LLY)
Lilly Forward-Looking Statement This press release contains "forward-looking statements" (as that term is defined in the United States Private Securities Litigation Reform Act of 1995) regarding CYRAMZA (ramucirumab) as a potential treatment for hepatocellular carcinoma. This press release reflects Lilly's current beliefs. However, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other risks, there can be no guarantee that this medicine will receive regulatory approval in this setting, or, if approved, that it will achieve intended benefits or become a commercially successful product. For further discussion of these and other risks and uncertainties that could cause actual results to differ materially from Lilly's expectations, please see the company's latest Forms 10-K and 10-Q filed with the U.S. Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements.
i Mayo Medical Laboratories. Test Catalog. Test ID: AFP. http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8162 . Accessed on June 18, 2015 . ii Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2012 Fact Sheet, Estimated Cancer Incidence, Mortality and Prevalence Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France : International Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr . Accessed on June 18, 2015 . iii CancerMPact®. Kantar Health. Available from: www.cancermpact.com . Accessed on June 15, 2015 .
| Refer to: | Tracy Henrikson; [email protected] ; (609) 240-3902 (Lilly) |
| Neil Hochman; [email protected] ; (212) 453-2067 (TogoRun) |
SOURCE Eli Lilly and Company