Eli Lilly’s Cyramza Succeeds in Phase III Trial

Eli Lilly and Company announced top-line data from its Phase III REACH-2 trial of Cyramza (ramucirumab) as a monotherapy second-line treatment for hepatocellular carcinoma (HCC), which is liver cancer.

The trial’s primary endpoint was overall survival (OS). The secondary endpoint was progression-free survival (PFS). The drug met both endpoints. It has now shown survival benefit in four aggressive, difficult-to-treat cancers in Phase III studies, as well as a monotherapy in gastric cancer and HCC. The others include non-small cell lung and colorectal cancer.

“Advanced liver cancer is an aggressive disease that has a poor prognosis—and for those that have elevated AFP levels, the prognosis is even more dismal,” said Levi Garray, Lilly Oncology’s senior vice president, global development and medical affairs, in a statement. “The expected survival of these patients is only a few months following first-line treatment if they don’t go onto second-line therapy. For this reason, Lilly is encouraged by the results of REACH-2 and the potential for Cyramza to benefit patients in this setting.”

REACH-2 is a global, randomized, double-blind, placebo-controlled Phase III trial that compared Cyramza to placebo in liver cancer patients who were intolerant to or had disease progression while on or after treatment with sorafenib and a high alpha-fetoprotein (AFP-High) level, which was defined as greater than or equal to 400 ng/mL. The trial began in 2015 and enrolled 292 patients across 20 countries in North America, Asia, Europe and Latin America.

The trial is called the first positive Phase III HCC trial in a patient population sorted by biomarker testing. About half of all advanced HCC patients have high levels of AFP and have the worst prognosis relative to the general HCC patient population.

AFP is a protein produced in early fetal development by the liver as well as by a variety of tumors, including HCC, hepatoblastoma, and nonseminomatous germ cell tumors of the ovary and testis. AFP is routinely tested in prenatal screening to evaluate the health and development of the fetus in pregnant women.

Cyramza is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that binds and blocks activation of VEGF Receptor 2. It is being evaluated in more than 12,000 patients in more than 708 clinical trials around the globe. In addition to being evaluated as a sole medication, it is being studied in combinations with other anti-cancer therapies for a broad range of tumor types.

The drug brought in $204.8 million in sales in the latest quarter. In the first three quarters of 2017 the drug brought in about $553.5 million. Lilly says it plans to submit the drug mid-year to regulatory authorities for this indication.

Competitors with the drug, at least for lung cancer, includes Roche’s Avastin, AstraZeneca’s Iressa, Bristol-Myers Squibb’s Opdivo, and Boehringer Ingelheim’s Gilotrif. Other drugs used to treat HCC include Bayer’s Nexavar and Regorafenib, and Opdivo.