Lenvatinib Shows Positive Results in Clinical Trial” Lenvatinib Approval Sought from FDA

Lenvatinib Approval Sought from FDA

August 18, 2014— Eisai, the manufacturer of lenvatinib (E7080), has submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for the use of lenvatinib to treat patients who have progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer (papillary, follicular, and variants).

The FDA review timeline will be set in mid-October, with the fastest possible decision to take place in 6 months.

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Lenvatinib Update

July 30, 2014— Lenvatinib, a new drug that has shown promise in a clinical trial for treating progressive differentiated thyroid cancer (papillary, follicular, and their variants) that does not respond to radioactive iodine, will receive accelerated assessment by the European Medicines Agency (EMA).

Lenvatinib is an oral multiple receptor tyrosine kinase (RTK) inhibitor. It is manufactured by Eisai.

Esai also reported that it soon plans to submit an application to the United States Food and Drug Administration (FDA) for Lenvantinib.

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Lenvatinib shows promising results as a treatment option for people with differentiated radioiodine-resistant thyroid cancer, according to a Phase III clinical trial reported at the meeting of the American Society of Clinical Oncology (ASCO).

Lead study author is Martin Schlumberger, M.D., Oncology Professor at University Paris Sud, France and ThyCa Medical Advisor.

A summary of the presentation at ASCO is here.

11/2013 and 6/2014: The U.S. Food and Drug Administration expanded the approved uses of Nexavar® (sorafenib) on November 22, 2013, and approved the drug to treat late-stage (metastatic) differentiated thyroid cancer.

In June 2014, Nexavar® approval widened to Europe.

Nexavar works by inhibiting multiple proteins in cancer cells, limiting cancer cell growth and division. The drug’s new use is intended for patients with locally recurrent or metastatic, progressive differentiated thyroid cancer that no longer responds to radioactive iodine treatment. Differentiated thyroid cancer includes papillary and follicular thyroid cancer and their variants such as Hurthle cell and tall cell.

Differentiated thyroid cancer can be challenging to treat, especially when unresponsive to conventional therapies,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval demonstrates the FDA’s commitment to expediting the availability of treatment options for patients with difficult-to-treat diseases.

The safety and effectiveness of Nexavar were established in a clinical study involving 417 participants with locally recurrent or metastatic, progressive differentiated thyroid cancer that does not respond to radioactive iodine treatment. Nexavar increased the length of time patients lived without the cancer progressing (progression-free survival) by 41 percent.

The FDA completed its review of Nexavar’s new indication under its priority review program. This program provides for an expedited, 6-month review for drugs that may offer a significant improvement in safety or effectiveness of the treatment, prevention or diagnosis of a serious condition. Nexavar also received orphan-product designation by the FDA because it is intended to treat a rare disease or condition.

The FDA approved Nexavar to treat advanced kidney cancer in 2005. In 2007, the agency expanded the drug’s label to treat liver cancer that cannot be surgically removed.

Nexavar is co-marketed by Bayer HealthCare Pharmaceuticals Inc., based in Wayne, New Jersey, and Onyx Pharmaceuticals, based in South San Francisco, California.

Genzyme announced on March 26, 2014, that the U.S. Food and Drug Administration (FDA) has approved the use of Thyrogen® (thyrotropin alfa for injection) in connection with a widened dose range of radioactive iodine (RAI) when used for thyroid remnant ablation. Genzyme’s announcement is here.

Update: July 1, 2013 – Applications Submitted in U.S. and Europe for Nexavar® (sorafenib) for Treatment of Radioactive Iodine-Refractory Differentiated Thyroid Cancer

July 1, 2013 — Bayer HealthCare and Onyx Pharmaceuticals have submitted applications to the U.S. Food & Drug Administration and the European Medicines Agency for approval of Nexavar® (sorafenib) for treating differentiated thyroid cancer (papillary, follicular, variants) that is locally advanced or metastatic and does not respond to radioactive iodine.

June 3, 2013 — At a plenary session at the American Society of Clinical Oncology’s Annual Meeting in Chicago, Illinois, positive results were presented from a Phase 3 Clinical Trial on the use of Nexavar® (sorafenib) tablets in thyroid cancer patients with differentiated thyroid cancer (papillary, follicular, variants) that had spread and did not respond to radioactive iodine.

The results will lead to regulatory submissions from the manufacturer to the U.S. Food and Drug Administration and to regulatory agencies globally.

The Phase 3 DECISION trial included 417 patients with locally advanced or metastatic differentiated thyroid cancer that did not respond to radioactive iodine. The trial was an international, multicenter, placebo-controlled study. The primary endpoint of the study was progression-free survival. Progression-free survival was evaluated by an independent radiological review committee, using Response Evaluation Criteria in Solid Tumors (RECIST).

Sorafenib significantly extended progression-free survival (PFS). The median PFS was 10.8 months among patients treated with sorafenib, compared to 5.8 months among patients receiving placebo. At the time of progression, patients had the option to cross over to open-label sorafenib at the discretion of the investigator. Median overall survival, a secondary endpoint of the trial, has not yet been reached in either arm of the study.

“While most patients with differentiated thyroid cancer are cured, there is a major treatment gap for patients whose cancer no longer responds to standard therapies,” said Marcia Brose, M.D., Ph.D., principal investigator of the DECISION trial, Assistant Professor in the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania, and a Medical Advisor of ThyCa: Thyroid Cancer Survivors’ Association.

“The DECISION results demonstrate sorafenib’s ability to extend progression-free survival compared to placebo in these patients, potentially providing a new treatment option for these patients,” she added.

The drug’s manufacturer, Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. reported that these results mean that a supplementary New Drug Application for sorafenib for the treatment of RAI-refractory differentiated thyroid cancer will be submitted in mid-2013 to the U.S. Food and Drug Administration, with additional submissions to follow globally. Sorafenib is currently approved in the U.S. for the treatment of patients with unresectable hepatocellular carcinoma and for the treatment of patients with advanced renal cell carcinoma. It is also approved in 100 countries.

“In the past 30 years, there have been no new treatment options approved for patients with radioactive iodine-refractory differentiated thyroid cancer,” said Pablo J. Cagnoni, M.D., Onyx Pharmaceuticals Executive Vice President, Global Research & Development and Technical Operations, “We are pleased with the results of the DECISION study, which demonstrate sorafenib’s activity in patients who have no other treatment options.”

Thyroid cancer has become the fastest-increasing cancer in the world in recent years and is the sixth most common cancer in women. There are more than 213,000 new cases of thyroid cancer annually worldwide. While the majority of differentiated thyroid cancers are treatable, RAI-refractory locally advanced or metastatic disease is more difficult to treat and is associated with a lower patient survival rate.