Eisai announces FDA approval of LENVIMA (lenvatinib) for treatment of RAI-refractory DTC

Eisai Inc. announced today that the U.S. Food and Drug Administration (FDA) approved the company's receptor tyrosine kinase inhibitor LENVIMA™ (lenvatinib) for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC). LENVIMA was approved following a priority review by the FDA, which is designated for drugs the FDA believes have the potential to provide a significant improvement in the treatment of a serious condition. LENVIMA demonstrated a statistically significant progression-free survival (PFS) prolongation and response rate in patients with progressive, differentiated thyroid cancer who had become refractory to radioactive iodine (RAI) therapy.

"In the pivotal Phase 3 SELECT clinical trial, recently published in the New England Journal of Medicine, treatment with LENVIMA resulted in a highly statistically significant improvement in progression-free survival and a high overall response rate in patients with locally recurrent or metastatic, progressive, RAI-refractory DTC," said Lori J. Wirth, M.D., study investigator and medical director of the Center for Head and Neck Cancers at the Massachusetts General Hospital. "The thyroid cancer community welcomes an agent that offers a significant, effective option for the treatment of differentiated thyroid cancer in patients who have progressed after becoming refractory to RAI therapy."

"The incidence of thyroid cancer has been increasing globally over the last 50 years and for patients with thyroid cancer that progresses following surgery and radioactive iodine treatment, the prognosis is often poor," said Gary Bloom, Executive Director of ThyCa: Thyroid Cancer Survivors' Association, Inc. "We are excited about the approval of LENVIMA, which may help address an unmet need as there are limited treatment options for patients with this type of thyroid cancer."

In the Phase 3 SELECT trial, which included 392 patients, LENVIMA demonstrated a highly statistically significant improvement in PFS in patients with RAI-R DTC compared with placebo. The median PFS, or delay in the length of time during and after treatment in which the disease did not worsen, with LENVIMA and placebo was 18.3 months and 3.6 months, respectively (HR 0.21; 95% CI: 0.16-0.28; p<0.001). In addition, an overall response rate, the sum of partial and complete response rates, of 65% was seen in patients treated with LENVIMA versus 2% with placebo, which included a complete response achieved in 2% of patients treated with LENVIMA versus 0% with placebo. Based on RECIST v1.1 criteria, a partial response is defined as a minimum 30% decrease in the sum of diameters of target lesions and a complete response is defined as a complete disappearance of tumors.

Serious risks seen in patients in the Phase 3 SELECT clinical trial were hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, proteinuria, renal failure and impairment, gastrointestinal perforation and fistula formation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of exogenous thyroid suppression and embryofetal toxicity. The most common adverse reactions observed in greater than or equal to 30% of LENVIMA-treated patients, in order of decreasing frequency, were: hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight decreased, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia (PPE) syndrome, abdominal pain, and dysphonia. The most common serious adverse reactions (at least 2%) were pneumonia (4%), hypertension (3%), and dehydration (3%).

It is important for doctors to know that when treating with LENVIMA, they may modify the dose as needed according to the recommendations provided in the prescribing information. Management of some adverse reactions may require the dose of LENVIMA to be withheld, reduced or discontinued. Upon resolution/improvement of an adverse reaction, treatment may be resumed at a reduced dose as suggested in the prescribing information. In the clinical trial, adverse events led to dose reductions in 68% of patients who received LENVIMA and 5% of patients who received placebo. Some patients will need to discontinue treatment for serious adverse reactions. In the trial, 18% of patients treated with LENVIMA and 5% who received placebo discontinued treatment. The most common adverse reactions (at least 10%) that resulted in dose reductions of LENVIMA were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%). The most common adverse reactions (at least 1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

"We are excited that LENVIMA was approved today by the FDA following the priority review designation received in October and look forward to offering this new treatment option to patients with progressive, RAI-refractory DTC," said Takashi Owa, Ph.D., Chief Innovation Officer at Eisai. "Eisai is committed to innovative research and product creation with the goal of helping patients with cancer."

Eisai is committed to ensuring patients have access to medicines from which they may benefit and is dedicated to working to ensure that our products are available to those who need them. Once LENVIMA is available, Eisai will provide reimbursement support programs for eligible patients.

LENVIMA™ (lenvatinib) will be available to order in the near future through specialty pharmacies Biologics, Inc. and Accredo.