Eisai’s US strategy takes a knock with farletuzumab failure

The logic of Eisai’s $325m takeover of Morphotek was dealt a major blow on Friday with the failure of farletuzumab in a second phase III ovarian cancer study. The molecule was Morphotek’s most advanced R&D project, and the 2007 acquisition of the private Pennsylvania-based biotech company had formed part of Eisai’s plan to build a US presence.

Although Eisai says it will analyse the positive trends it says it saw in certain patient subsets before making a final decision, it seems unlikely that development of farletuzumab will continue. The project had flunked its first phase III trial in December 2011, and clinicaltrials.gov now lists no other active studies.

Farletuzumab (MORAb-003) is a humanised IgG1 monoclonal antibody designed to bind to the alpha folate receptor that is expressed on the surface of several cancers, including ovarian. It is therefore a variation on the folate-targeting mechanism used by several R&D projects against ovarian cancer.

The most advanced of these is Endocyte’s vintafolide (EC145), a small molecule comprising a vinblastine derivative linked to folic acid. Vintafolide, now awaiting EU approval together with a companion diagnostic for folate receptor-positive ovarian cancer, was the subject of one of the biggest alliances of 2012 when Merck & Co licensed it for $120m up front.

Long shot

As far as farletuzumab goes, however, a regulatory filing looks like a long shot after its failure in the phase III FAR-131 trial of second-line treatment of 1,080 women with platinum-sensitive ovarian cancer in which it was added on top of standard-of-care carboplatin and a taxane.

Eisai said neither 1.25mg/kg nor 2.5mg/kg of farletuzumab gave a statistically significant improvement in progression-free survival, the primary endpoint, compared with standard of care alone. A post hoc data dredge revealed trends towards improved PFS in certain undisclosed patient subsets, and a safety analysis threw up immune-mediated events in addition to those typically expected from the carboplatin and taxane chemotherapy.

Ovarian cancer is a highly intractable indication characterised by numerous late-stage disappointments (Therapeutic Focus - Disappointment a recurring theme in ovarian cancer pipeline, December 20, 2011). Farletuzumab’s earlier phase III failure was in the FAR-122 study of 417 patients with platinum-resistant disease, terminated for futility on the advice of its data-monitoring committee.

Still, consensus forecasts for farletuzumab were very conservative despite its late-stage status. Consensus was for a 2014 launch, with sales reaching a modest $76m by 2018, yielding a 75% risk-adjusted NPV of $235m, according to EvaluatePharma.

US expansion

Morphotek was acquired by Eisai when the Japanese company had set its sights on US expansion. Eisai also has research and discovery operations in Massachusetts; it bought four oncology drugs from Ligand Pharmaceuticals in 2006, and four years later licensed US rights to Arena Pharmaceuticals’ late-stage obesity candidate lorcaserin.

Since being taken over Morphotek has operated relatively freely of Eisai as a US subsidiary, and still boasts several antibody-based pipeline projects. The most advanced after farletuzumab are amatuximab (MORAb-009), in phase II for mesothelioma, an indication for which it recently received orphan drug status, and MORAb-004, in two phase II trials in melanoma and colorectal cancer.

While the farletuzumab failure might not totally destroy the rationale for buying Morphotek it will remind Eisai how risk-prone development-stage acquisitions are.