FDA Approves Lilly's CYRAMZA® (ramucirumab), A Biomarker-Driven Therapy For Hepatocellular Carcinoma

FDA approved (See the press release below,) Cyramza for the treatment of liver cancer patients who have failed on Bayer's Nexavar on Monday, the 13th April 2019. The drug faces competition in the field full of treatment solutions, and it is going up against a bunch of big-name rivals. The silver streak is that Cyramza has a targeted green light, approving it specifically to treat patients with high levels of the glycoprotein alpha-fetoprotein (AFP), a biomarker that usually has unfavourable outcomes that affects about 40% of patients with hepatocellular carcinoma, the most common form of liver cancer, according to Lily. The approval is based on the results from the REACH-2 study, the first positive Phase 3 HCC trial in a biomarker-selected patient population. REACH-2 is a global, randomized, double-blind, placebo-controlled Phase 3 study of CYRAMZA compared to placebo in patients with HCC who have been treated with sorafenib and are AFP-High (AFP ≥400 ng/mL).

"This new indication for CYRAMZA further reinforces Lilly's ongoing commitment to delivering meaningful medicines that are tailored for people with advanced cancers and the physicians that work in partnership with them, Our work is focused on helping people who are living with cancer and Lilly is making strides in its efforts to develop precision medicine-based therapies for patients, to give them a fighting chance against their disease." said Anne White, president of Lilly Oncology. "

 "This approval of CYRAMZA is an important step forward in the treatment of advanced hepatocellular carcinoma, While there have been some recent advances, there are still limited treatment options for people with this type of cancer and – until now – there was no treatment option specifically indicated for patients with increased alpha-fetoprotein concentrations. These patients can have more aggressive disease and a poorer prognosis with increased angiogenesis." said Andrew X. Zhu, M.D., director of Liver Cancer Research at Massachusetts General Hospital Cancer Center, professor of medicine at Harvard Medical School and principal investigator of the REACH-2 trial.

 

CYRAMZA (ramucirumab) Injection
Company:  Eli Lilly and Company
Application No.:  125477
Approval Date: 4/21/2014

Persons with disabilities having problems accessing the PDF files below may call (301) 796-3634 for assistance. (FDA)

• Approval Letter(s) (PDF)
• Printed Labeling (PDF)
• Summary Review (PDF)
• Officer/Employee List (PDF)
• Office Director Memo (PDF)
• Cross Discipline Team Leader Review (PDF)
• Medical Review(s) (PDF)
• Chemistry Review(s) (PDF)
• Pharmacology Review(s) (PDF)
• Statistical Review(s) (PDF)
• Microbiology/Virology Review(s) (PDF)
• Clinical Pharmacology Biopharmaceutics Review(s) (PDF)
• Risk Assessment and Risk Mitigation Review(s) (PDF)
• Proprietary Name Review(s) (PDF)
• Other Review(s) (PDF)
• Administrative Document(s) & Correspondence (PDF)

Press Release (For the complte Press release, follow the link bellow. )

 

INDIANAPOLIS, May 13, 2019 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that the U.S. Food and Drug Administration (FDA) has approved CYRAMZA® (ramucirumab injection, 10 mg/mL solution), as a single agent, for the treatment of patients with hepatocellular carcinoma (HCC) who have an alpha-fetoprotein (AFP) of ≥400 ng/mL and have been treated with sorafenib. Concurrent with this FDAapproval – the fifth for CYRAMZA – the FDA has also removed the boxed warning from the CYRAMZA labeling.

HCC is the most common form of liver cancer, which is the fourth-leading cause of cancer-related death worldwide.1,2 In the U.S., liver cancer is one of the few major cancers with incidence rates that continue to rise every year3 and is the fastest rising cause of cancer death.4

AFP is a prognostic biomarker that can be assessed through a simple blood test, now allowing physicians to select patients who may benefit from treatment and to monitor disease progression in advanced HCC.5-8

"This approval of CYRAMZA is an important step forward in the treatment of advanced hepatocellular carcinoma," said Andrew X. Zhu, M.D., director of Liver Cancer Research at Massachusetts General Hospital Cancer Center, professor of medicine at Harvard Medical School and principal investigator of the REACH-2 trial. "While there have been some recent advances, there are still limited treatment options for people with this type of cancer and – until now – there was no treatment option specifically indicated for patients with increased alpha-fetoprotein concentrations. These patients can have more aggressive disease and a poorer prognosis with increased angiogenesis."

This approval is based on the results from the REACH-2 study, the first positive Phase 3 HCC trial in a biomarker-selected patient population. REACH-2 is a global, randomized, double-blind, placebo-controlled Phase 3 study of CYRAMZA compared to placebo in patients with HCC who have been treated with sorafenib and are AFP-High (AFP ≥400 ng/mL).

"This new indication for CYRAMZA further reinforces Lilly's ongoing commitment to delivering meaningful medicines that are tailored for people with advanced cancers and the physicians that work in partnership with them," said Anne White, president of Lilly Oncology. "Our work is focused on helping people who are living with cancer and Lilly is making strides in its efforts to develop precision medicine-based therapies for patients, to give them a fighting chance against their disease."

"There is an urgent need for new liver cancer treatments that take into account the things that make each patient unique, particularly for those with advanced stages of the disease," said Donna Cryer, president and CEO of the Global Liver Institute. "We welcome this approval and the hope it may bring to people living with this devastating disease."

This approval adds to the body of evidence demonstrating the safety of CYRAMZA. The FDA has removed the boxed warning from the CYRAMZA labeling which highlighted warnings pertaining to hemorrhage, gastrointestinal perforation and impaired wound healing. The updated CYRAMZA labeling continues to provide important information on these specific risks, as well as other adverse events, to physicians and the patients that work in partnership with them so that they can make informed decisions regarding cancer care.

The labeling for CYRAMZA contains warnings and precautions for hemorrhage and GI hemorrhage, including severe and sometimes fatal events; gastrointestinal (GI) perforations, a potentially fatal event; impaired wound healing; arterial thromboembolic events (ATEs), including serious and sometimes fatal events; hypertension; infusion-related reactions; worsening of pre-existing hepatic impairment, reversible posterior leukoencephalopathy syndrome (RPLS); proteinuria including nephrotic syndrome; thyroid dysfunction; and embryo-fetal toxicity. CYRAMZA should be permanently discontinued in patients who experience severe bleeding, a GI perforation, an ATE, uncontrolled hypertension, RPLS, or nephrotic syndrome. CYRAMZA should be withheld prior to surgery and discontinued if a patient develops wound healing complications.

The most common adverse reactions (all Grades) observed in single agent CYRAMZA-treated HCC patients at a rate of ≥15 percent and ≥2 percent higher than placebo were fatigue (36% vs 20%), peripheral edema (25% vs 14%), hypertension (25% vs 13%), abdominal pain (25% vs 16%), decreased appetite (23% vs 20%), proteinuria (20% vs 4%), nausea (19% vs 12%), ascites (18% vs 7%). Please see Important Safety Information below. 
 

Abbreviations: BSC = best supportive care; CI = confidence interval
* 26 of 172 events in CYRAMZA-treated patients and 9 of 86 events in placebo-treated patients were deaths.
† Does not include stable disease; all responses were partial.
‡ Disease progression and tumor response were assessed by investigators in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

The REACH-2 study design was informed by findings from the REACH study, which uncovered AFP as a potential predictive biomarker in HCC.

CYRAMZA was discontinued due to adverse reactions in 18 percent of CYRAMZA-treated patients, with proteinuria being the most frequent (2%). The most common adverse reactions of any grade observed in single agent CYRAMZA-treated HCC patients at a rate of ≥15 percent and ≥2 percent higher than placebo were fatigue (36%), peripheral edema (25%), hypertension (25%), abdominal pain (25%), decreased appetite (23%), proteinuria (20%), nausea (19%), and ascites (18%). The most common serious adverse reactions with CYRAMZA were ascites (3%) and pneumonia (3%). The most common laboratory abnormalities occurring in >30 percent of patients and ≥2 percent higher than placebo were thrombocytopenia (46%), hypoalbuminemia (33%), and hyponatremia (32%).

Lilly has also submitted applications for marketing authorization in the European Union and Japan based on the REACH-2 results and regulatory action in these geographies is expected in mid-2019.

The National Comprehensive Cancer Network® (NCCN®) Guidelines recognize ramucirumab (CYRAMZA®) as a Category 1 recommendation treatment option for second-line HCC patients who have AFP ≥400 ng/mL and have been treated with sorafenib.9

With this approval, Lilly has now received five FDA approvals for CYRAMZA to treat four of the world's most deadly cancers. These approvals are based on a demonstrated survival benefit in Phase 3 studies of advanced forms of gastric and gastroesophageal junction adenocarcinoma, metastatic non-small cell lung cancer, metastatic colorectal cancer, and AFP-High HCC. Two of these studies have shown the proven benefit of CYRAMZA as a single agent in treating advanced gastric cancer and AFP-High HCC.

Additionally, Lilly recently announced top-line results from its Phase 3 study of CYRAMZA in EGFR-mutated metastatic non-small cell lung cancer. These results will be presented at the American Society of Clinical Oncology 2019 Annual Meeting and are the basis for global regulatory submissions planned in mid-2019.

Refer to: 
Tracy Henrikson; tracy.henrikson@lilly.com; 609-454-7116 (media)
Kevin Hern; hern_kevin_r@lilly.com; 317-277-1838 (investors)

SOURCE Eli Lilly and Company/