Eisai Makes Oncology Debut With Halaven, But Development Question Marks Remain

TOKYO - Eisai gained its first U.S. approval for one of its in-house developed oncology products, Halaven (eribulin), but the company's blockbuster expectations may be tempered by progression-free survival data that did not meet secondary endpoints.

U.S. FDA approved Halaven Nov. 15 for the treatment of metastatic breast cancer in patients who have received at least two prior chemotherapy regimens, including an anthracycline and a taxane, for late-stage disease.

Halaven was approved based on data from a global Phase III trial which showed that Halaven patients survived a median of 2.5 months longer than patients in the treatment of physician's choice arm, which included any single-agent chemotherapy, biologic or radiotherapy deemed most suitable by the physician.

But the drug failed to show statistically significant superiority for the secondary endpoint of progression-free survival. Eribulin posted progression-free survival of 3.7 months, compared to the TPC arm of 2.2 months.

Eisai has touted the drug as having the potential to reach $1 billion in peak sales, but to do so, Halaven will have to gain both first- and second-line approval for breast cancer, Credit Suisse analyst Fumiyoshi Sakai told PharmAsia News. Still, upon news of the Nov. 15 approval Sakai forecast worldwide peak sales of ¥80 billion ($963.28 million) in a Nov. 16 note.

According to a four-year review of FDA's oncology approval track record, the agency found that between 2006 and 2010 overall survival was used in only 17.1 percent of FDA drug actions, compared to overall response rate at 39.5 percent, and progressions-free survival at 39.5 percent of FDA actions (Also see "FDA Official Stresses "Flexibility" On Speeding Approval Of Drugs That Truly Stand Out" - Pink Sheet, 27 Oct, 2010.).

Additional Indications Hinge On Improving Progression-free Survival Data

Already in the small minority of drugs to gain approval via overall survival, Eisai's ability to gain additional indications for Halaven may hinge on improving the drug's progression-free survival data. Eisai is continuing to collect progression-free survival data and expects to release new data at the annual ASCO meeting in June 2011 in Chicago.

Eisai is planning to file Halaven for approval in 2012 for second-line treatment of metastatic breast cancer, and also has ongoing U.S. and European Phase II trials for the drug in prostate cancer, sarcoma, and non-small cell lung cancer. Eisai filed simultaneous applications for Halaven in the U.S., EU and Europe, and the company said during the press conference it intends to add Japan to its Phase III trials for additional indications based on promising Phase II data from Europe. "In principal we want to have a global trial approach," an Eisai spokesman said during the conference.

Initially, concerns over the drug's prospects were raised when U.S. FDA moved the initial action date from Sept. 30 to Dec. 30, according to Citi analyst Hidemaru Yamaguchi. But Yamaguchi and Credit Suisse's Sakai view the early approval as positive implication for the drug's development.

Halaven also managed to gain approval days ahead of the patent loss of Alzheimer's disease blockbuster Aricept (donepezil). Eisai said it will launch Halaven Nov. 25, the day before generic Aricept is launched. Eisai has made a big push to move patients to a higher dosage of Aricept to stem the damage caused by patent loss, but according to data from IMS Health, the drug's dosage conversion rate has been stalled at 3 percent since the higher dosage was launched in July (Also see "Eisai And Pfizer Begin Undertaking To Switch Appropriate Patients To High-dose Aricept" - Scrip, 27 Jul, 2010.). However, Sakai wrote in the Credit Suisse note that overall Aricept prescriptions appear to have increased following the launch of high-dose Aricept.

Eisai set its sights on becoming a major player in the oncology market just a few years ago, starting in earnest with its acquisition of MGI Pharma in March 2008. Thanks largely to MGI, Eisai has its oncology marketing structure in place in the U.S. and will not need to hire new staff for Halaven's launch.

Filed simultaneously in the U.S. and Japan, both countries granted Halaven priority review status, so the company is expecting approval in Japan in the early half of 2011.

For a company's first in-house oncology launch, Halaven requires a complex synthesis process, according to Citi's Yamaguchi, which raises the risk that the drug's cost-of-goods-sold will rise. Halaeven is a microtubule inhibitor synthesized from a compound derived from a sea sponge found off the coast of the Miura Peninsula in Japan.

- Daniel Poppy ([email protected])