Lilly's Cyramza Enters Competitive Hepatocellular Carcinoma Market with Biomarker-Driven Approval

Recently, the U.S. FDA announced the approval of Eli Lilly's Cyramza (ramucirumab) as a monotherapy for the treatment of patients with hepatocellular carcinoma.

Cyramza is a VEGF receptor 2 (VEGFR2) antagonist that inhibits angiogenesis by binding to VEGFR2 and blocking its interaction with the ligands VEGF-A, VEGF-C, and VEGF-D. The unique advantage of Cyramza over its competitors lies in its specific indication for the treatment of patients with elevated levels of the glycoprotein alpha-fetoprotein (AFP).

AFP affects approximately 40% of patients with hepatocellular carcinoma, and there are currently no treatment options specifically designed for patients with elevated AFP levels. Patients with elevated AFP levels have a particularly poor prognosis; once first-line therapy fails, their expected survival is only 3–5 months if left untreated.

The approval of Cyramza was based on a randomized, double-blind, placebo-controlled, multicenter Phase 3 clinical trial involving 292 patients with advanced hepatocellular carcinoma (HCC). These patients had alpha-fetoprotein (AFP) levels exceeding 400 ng/mL and were either intolerant to sorafenib or experienced disease progression following sorafenib treatment. The primary endpoint of the trial was overall survival (OS). The results demonstrated that the median OS was 8.5 months in the treatment group compared to 7.3 months in the placebo group (HR: 0.71; 95% CI: 0.53, 0.95; p=0.020).

Next, Cyramza will face a series of major competitors. It must compete with Bayer’s Stivarga and contend with pressure from Merck & Co.’s blockbuster drug Keytruda. In addition, Bristol Myers Squibb’s Opdivo has been approved for second-line treatment of liver cancer, and Exelixis’ Cabometyx also received approval for the corresponding indication in January, making the market competition extremely intense.

Fortunately, the FDA removed the boxed warnings for bleeding, gastrointestinal perforation, and impaired wound healing from Cyramza’s labeling, a move that will help enhance its competitiveness.

Cyramza missed its primary endpoint in a Phase 3 trial in 2014, failing to significantly increase or prolong patient survival. However, in April 2018, a subsequent trial finally yielded positive results, demonstrating that the drug could extend patient survival and slow tumor progression. Nevertheless, Cyramza still has a long road ahead.

In the first quarter, competitor Bayer achieved sales of €284 million ($319.7 million) from Nexavar and Stivarga, representing year-over-year growth of 13.6% and 38.6%, respectively. Cyramza’s global sales in the first quarter amounted to $183.6 million, with a modest growth rate of only 8%.

Eli Lilly is also actively striving to maximize the benefits of Cyramza and is seeking potential approval for its indication in non-small cell lung cancer (NSCLC).

On March 13, Eli Lilly announced that the combination therapy of Cyramza and Roche’s Tarceva met the primary endpoint of improving progression-free survival in a pivotal Phase 3 trial for previously untreated metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations. (Compiled by Fan Dongdong, Sina Medicine)

Reference Source: Lilly plays up Cyramza's biomarker edge in crowded liver cancer field