Merck KGaA hit by disappointing Erbitux results from COIN study

German drug major Merck KGaA suffered a setback on September 23, on the news that one of its leading products, the colorectal cancer agent Erbitux (cetuximab), failed to extend the lives of patients or prevent disease progression. This sent the firm's share price 2.6% to 67 euros, despite Merck's separate presentation showing that Erbitux helped normal KRAS patients live an average 3.5 months longer than those given chemotherapy alone.

Both sets of findings were presented at the joint 15th Congress of the European Cancer Organization (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO) in Berlin, Germany.

The Medical Research Council (MRC), a UK-based, publicly-funded organization, revealed the initial results of the independent Phase III COIN(a) study, which did not meet its primary endpoint of overall survival. The COIN study was designed to evaluate whether the addition of Erbitux to one of two oxaliplatin-based chemotherapy regimens significantly improved outcomes in previously untreated metastatic colorectal cancer (mCRC) patients with KRAS wild-type tumors. The median OS was not statistically significant at 17.0 months in the Erbitux treatment arm compared to 17.9 months for the chemotherapy-alone group (hazard ratio [HR] 1.038; p=0.68).

'Imbalances in the chemotherapy administered between the different study arms were reported previously in the interim safety analysis,' explained Wolfgang Wein, executive vice president, oncology, at Merck Serono, a division of Merck KGaA. 'Further analysis of the dose intensity and second-line treatment, and other factors, such as the advanced disease of patients in the study, are ongoing to determine why the COIN results are not aligned with existing evidence from the other randomized, first-line studies, including the significant increase in overall survival achieved with the CRYSTAL study,' he added.

Merck says that results from the pivotal Phase III CRYSTAL(b) trial also presented the same day, demonstrated that the addition of Erbitux to the standard first-line FOLFIRI chemotherapy regimen significantly improved OS in patients with KRAS wild-type tumors (23.5 versus 20.0 months, HR 0.796, p=0.0094).(2) In addition, results from the Phase II OPUS(c) study, which investigated the benefit of adding Erbitux to the FOLFOX regimen in KRAS wild-type patients, demonstrated: significant improvement in progression-free survival (8.3 vs 7.2 months, HR 0.567, p=0.0064); significant improvement of response rate (57,3% vs 34,0%, p=0.0027); and OS was 22.8 vs 18.5 months (HR 0.855, p=0.3854).

Erbitux is sold in the USA by drug majors Eli Lilly and Bristol-Myers Squibb, while Merck sells it elsewhere. Sales of the drug outside the U.S. are not likely to reach 1 billion euros ($1.48 billion) a year before 2011, Mr Wein said. The drug generated second-quarter 2009 turnover of 171 million euros for the German firm, up 18% on the like, year-earlier period. The European Union in July rejected the drug as a treatment for a form of lung cancer. It is approved for use in colorectal as well as head and neck tumors.