Eli Lilly and Company announced 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 FDA approval – 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. In the U.S., liver cancer is one of the few major cancers with incidence rates that continue to rise every year and is the fastest rising cause of cancer death.
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.
"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).
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"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%).