Eisai submits supplemental new drug application to FDA for Lenvima

Eisai submitted a supplemental new drug application to the FDA to seek approval for lenvatinib as a frontline therapy for patients with hepatocellular carcinoma.

The submission included positive results from the international, multicenter, open-label, randomized, noninferiority phase 3 REFLECT trial, designed to evaluate the efficacy and safety of lenvatinib (Lenvima, Eisai), a multiple receptor tyrosine kinase inhibitor, compared with sorafenib (Nexavar, Bayer) in 954 previously untreated patients with unresectable hepatocellular carcinoma.

Researchers randomly patients to receive lenvatinib (n = 478) — 12 mg or 8 mg once daily, depending on body weight — or 400 mg sorafenib twice daily (n = 476) until disease progression or unacceptable toxicity.

OS served as the primary endpoint. Secondary endpoints included PFS, time to progression and objective response rate.

Patients treated with lenvatinib demonstrated superior OS (13.6 months vs. 12.3 months; HR = 0.92; 95% CI, 0.79–1.06), median PFS (7.4 months vs. 3.7 months; HR = 0.66; 95% CI, 0.57–0.77), median time to progression (8.9 months vs. 3.7 months; HR = 0.63; 95% CI, 0.53–0.73) and ORR (24% vs. 9%; OR = 3.13; 95% CI, 2.15-4.56) compared with those treated with sorafenib.

In the lenvatinib arm, the most common treatment-related adverse events included hypertension, diarrhea, decreased appetite, decreased weight and fatigue.

In total, 9% of patients treated with lenvatinib and 7% of patients treated with sorafenib discontinued treatment due to treatment-related adverse events.

“The liver cancer community has been long awaiting additional first-line treatment options for this advanced form of the disease, and today's file submissions are an important next step to potentially being able to offer patients and doctors another option,” Kenichi Nomoto, chief scientific officer of the oncology business group at Eisai, said in a company-issued release. “Based on the activity observed in the REFLECT trial, Eisai is eager to work with the U.S. FDA and regulatory agencies worldwide with the hope of quickly bringing lenvatinib to patients with liver cancer.”

Lenvatinib is currently approved for the monotherapy treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer and in combination with everolimus (Afinitor, Novartis) to treat patients with advanced renal cell carcinoma following one prior antiangiogenic therapy.