A Pillar Of Eisai’s Growth Strategy Misses Primary Endpoint In First Phase III Trial

Eisai-acquired Morphotek lead candidate farletuzumab sees disappointing results in platinum-sensitive ovarian cancer.

TOKYO – Eisai Co. Ltd.’s farletuzumab, one of the five major products in the company’s mid-term growth plan, has returned disappointing Phase III results in platinum-sensitive ovarian cancer, not meeting the primary endpoint in the compound’s first Phase III attempt.

The company announced Jan. 11 farletuzumab failed to meet the primary endpoint for significant progression-free survival in a multicenter, comparative study of 1,100 patients in first relapse. Eisai suggested a small glimmer of hope – a “trend toward improved PFS in some patient subsets” – but would not specify additional details in response to inquiries. inquiries. Eisai would only reaffirm that additional analysis of the results will “determine a new development strategy.”

Farletuzumab is also currently undergoing a Phase II trial for non-small cell lung cancer. The trial completed recruitment for the Phase II trial, but Eisai would not specify when results will be available.

Eisai CEO Haruo Naito said in November 2012 during a second quarter earnings meeting that the company was preparing simultaneous farletuzumab submissions in Japan, U.S. and EU by the fourth quarter of 2012, which will likely be walked back now.

Toward More Personalized Medicine

Morphotek Inc., the Eisai subsidiary responsible for farletuzumab’s development, partnered with Biocare Medical LLC in 2011 to develop an immunohistochemical diagnostic kit to detect folate receptor alpha (FRA), farletuzumab’s target. FRA is over-expressed in a number of epithelial-derived tumors. The company said more than 90% of ovarian cancers show FRA over-expression, and CEO Naito estimates 40% of NSCLC patients are FRA positive.

Tapping into a large portion of the ovarian cancer and NSCLC populations in an era of personalized medicine holds great appeal to the company. Naito cited farletuzumab – along with Halaven, perampanel, lenvatinib and avatrombopag – as the five major projects of the “Hayabusa,” Eisa’s mid-term strategy plan to become a more substantial global power.

Halaven (eribulin) received approval in the U.S. in 2010, but last year missed primary endpoints in a head-to-head Phase III superiority study against Xeloda (capecitabine). Much of the excitement around eribulin at the time of its approval was the likelihood of extending its label, which is now drawn into question (Also see "Eisai Will Try For Halaven Label Expansion, Despite Phase III Failure" - Pink Sheet, 10 Jul, 2012.).

Perampanel, approved as Fycompa in the U.S. in October 2012, offers a new mechanism of action – only the second in a decade – but the epilepsy market is crowded with generics. Epilepsy accounts for only 2% of the worldwide pharmaceutical market (Also see "With New Mechanism, Can Eisai’s Fycompa Make Its Mark In Epilepsy?" - Pink Sheet, 29 Oct, 2012.).

Lenvatinib, a tyrosine kinase inhibitor, is currently in global Phase III trials for thyroid cancer. The trials are financed by development firm SFJ Pharmaceuticals Inc., but Eisai is still in charge of development (Also see "Pfizer De-Risks Renal Drug Development Via SFJ Pharma Deal; Plans Asia Trials" - Scrip, 11 Jan, 2012.).

Eisai believes avatrombopag has potential to be a best-in-class thrombopoietin agonist for idiopathic thrombocytopenic purpura and thrombocytopenia associated with liver disease. Global Phase III trials are ongoing for ITP and Phase II trials are ongoing for TLD.

Eisai touted farletuzumab as a first-in-class monoclonal antibody for FRA throughout development. It was granted orphan status by U.S. FDA in 2006 and by EMA in 2008 and received support from FDA to file only a single pivotal study in first relapse platinum-sensitive ovarian cancer. At a R&D meeting in 2011, Eisai talked about pushing into Phase II trials for at least three new indications for farletuzumab, highlighting the appeal of a compound it believes will target FRA.

Merck Moving In With FRA-positive Cancer Candidate Vintafolide

Meanwhile, Merck & Co. Inc. acquired its own candidate for FRA-positive cancers in April 2012 with the acquisition of development and commercialization rights for Endocyte Inc.’s vintafolide for an upfront payment of $120 million and up to $880 million in milestones.

Merck and Endocyte said in October 2012 they remain on track to file vintafolide in the EU in the fourth quarter of 2012 for platinum-resistant ovarian cancer. The two companies are also developing the drug for NSCLC, and Merck CEO Kenneth Frazier singled out vintafolide in Merck’s third quarter earnings call as compounds that “could have utility in a variety of tumor types.”

Endocyte retains rights to vintafolide’s companion diagnostic etarfolatide. The companies will have to submit three separate filings in the EU for ovarian cancer, individual filings for vintafolide, etarfolatide, and folic acid, which is used to improve image quality for the diagnostic. The three filings will be submitted simultaneously and the review cycle is expected to be the same for all three.

The conditional approval in Europe is based primarily on Phase IIb data from the PRECEDENT trial. U.S. FDA appears more wary than EMA in this case; the U.S. agency did not recommend Endocyte to pursue an accelerated approval based on the available data – unlike their stance on Eisai’s farletuzumab (Also see "Merck Gains Phase III Drug/Companion Diagnostic In Deal With Endocyte" - Pink Sheet, 16 Apr, 2012.).

Endocyte and Merck are collecting additional data for the U.S. in the Phase III PROCEED trial for platinum-resistant ovarian cancer. Endocyte CEO Ron Ellis expects to receive data in the first half of 2014.

[Editor’s note:This story was contributed by PharmAsia News, which provides highly specialized coverage of Asia business and regulatory developments in biopharma.]