Daiichi Sankyo Co. Ltd. has suspended the development of its investigational HER3-inhibiting antibody patritumab in non-small cell lung cancer (NSCLC) after disappointing efficacy results in the first part of a global Phase III study.

The HER3-Lung trial has been halted after a recommendation from the independent data monitoring committee, which concluded that the pre-defined efficacy criteria to continue to part B of the study had not been met, although there were no safety concerns.

The firm said it still planned to present data from the trial at an upcoming meeting, and would continue to examine the findings to decide on the next steps for the NSCLC indication.

HER3-Lung had been investigating patritumab in combination with erlotinib (Roche's EGFR inhibitor Tarceva) in patients with locally advanced or metastatic NSCLC, stratified by tumor expression of heregulin rather than EGFR mutation. Expression of heregulin, a member of the neuregulin protein family and a HER3 ligand, was being assessed as a predictive biomarker in the disease.

The rationale for combination with erlotinib was that HER3 must bind with EGFR (or HER2) to stimulate cancer cell growth, with heregulin enhancing this interaction.

Part A of the study was assessing progression-free survival and the second part was due to look at overall survival as a primary endpoint in patients with high heregulin expression.

Daiichi Sankyo stressed that patritumab's ongoing Phase II program in untreated recurrent/metastatic head and neck cancer in combination with cetuximab (Merck KGAA's Erbitux) and a platinum agent would continue unaffected. "This particular result [in NSCLC] does not directly affect the science of patritumab in other settings," said Dr. Antoine Yver, the Japanese company's EVP and global head, oncology R&D.

Informa's Biomedtracker currently gives the antibody a 10% chance of US approval in head and neck cancer, the same as average.

The asset, also known as U3-1287, was originally acquired with U3 Pharma AG, the small private German oncology venture that Daiichi Sankyo bought for around $160m in 2008 but shut down late last year ([A#28151202003]).

While the suspension is a blow, Daiichi Sankyo already has three other Phase III-stage oncology molecules in development: the FLT3 inhibitor quizartinib for acute myeloid leukemia; the CSF-1R inhibitor pexidartinib for tenosynovial and tendon sheath giant cell tumor; and tivantinib, a MET inhibitor for second-line hepatocellular carcinoma (with ArQule Inc.).

The company is strategically building its oncology interests ahead of the first loss of exclusivity for its top product, the antihypertensive olmesartan, this year. It currently has virtually no commercial presence in the sector, but is investing heavily, including in acquisitions ([A#28160412003]).

Nektar Etirinotecan Deal

While one pipeline project looks to have been lost, Daiichi Sankyo also announced it had acquired exclusive marketing rights in Europe, Switzerland and Turkey to Nektar Therapeutics Inc.'s Onzeald (etirinotecan pegol). [See Deal]

The deal involves a $20m upfront payment plus up to $60m in regulatory and sales milestones and "significant double-digit royalties" on net sales.

The drug is the first long-acting topoisomerase I inhibitor to give prolonged plasma exposure but lower average concentrations compared with standard irinotecan, and is designed to accumulate in tumors while improving tolerability.

Onzeald has already completed the 852-patient, Phase III single-agent BEACON study in advanced breast cancer previously treated with an anthracycline, taxane, and capecitabine. Nektar sees a possible conditional approval and launch in Europe next year, based on a subgroup analysis from the trial in patients with a history of brain metastases. These are diagnosed in 10-30% of patients with advanced breast cancer, a disease in turn diagnosed in around 470,000 people a year in Europe.

Onzeald gave a 5.2-month increase in median overall survival in the 67-patient brain metastases subgroup versus single-agent chemotherapy of physician's choice (TPC; 10 months vs. 4.8 months; p<0.01). in="" the="" overall="" study,="" overall="" survival="" was="" 2.2="" months="" longer="" on="" onzeald="" compared="" with="" tpc="" (12.4="" months="" vs.="" 10.3="" months;="" p="">

An EU filing for conditional approval in this setting is planned by Nektar this month, following the granting of an accelerated assessment procedure. Nektar will fund a subsequent confirmatory trial in around 350 patients with advanced disease and brain metastases, data from which will also be used for a planned US NDA.

Daiichi Sankyo Loses One, Gains One In Oncology

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