Merck Withdraws European Filing for Erbitux in NSCLC

Darmstadt, Germany, September 18, 2012 – Merck announced today the strategic decision to voluntarily withdraw the marketing authorization application (MAA) to the European Medicines Agency (EMA) of a label extension for Erbitux® (cetuximab) in combination with standard first-line platinum-based chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with high epidermal growth factor receptor (EGFR) expression. The decision to withdraw the application was based on feedback from European regulatory authorities, indicating that further data would be required. The decision does not alter the proven utility of Erbitux in its already approved indications in metastatic colorectal cancer (mCRC) and squamous cell carcinoma of the head and neck (SCCHN).

“We are disappointed that we have not been able to move forward with the filing in NSCLC but it has become apparent that further data will be required to support the clinical utility of Erbitux in this specific population,” said Dr. Annalisa Jenkins, Head of Global Drug Development and Medical for the Merck Serono division. “We continue to advance our oncology pipeline, for example also by planning to initiate a randomized Phase III trial of TH-302 in patients with advanced first-line pancreatic cancer together with our partner Threshold.”

Merck’s partner Threshold Pharmaceuticals, Inc. announced on 17 September 2012 that data from a randomized open-label Phase IIb clinical trial of investigational hypoxia-targeted drug TH-302 in patients with advanced pancreatic cancer will be presented at the European Society for Medical Oncology (ESMO) 2012 Congress in Vienna taking place September 28 – October 2, 2012. Threshold announced in February 2012 that the study met its primary endpoint demonstrating a statistically significant 63% improvement (p=0.005) in progression free survival (PFS) for patients treated with TH-302 and gemcitabine versus gemcitabine alone. This represented a 2-month increase in PFS for patients treated with TH-302.

New findings on overall survival, which was a secondary endpoint of the study, indicate that patients treated with gemcitabine alone had a median overall survival of 6.9 months compared with 9.2 months for patients treated with 340 mg/m2 TH-302 plus gemcitabine (HR: 0.955, 95% CI: 0.67–1.37, p=0.800) and 8.7 months for patients treated with 240 mg/m2 TH-302 plus gemcitabine (HR: 0.960, 95% CI: 0.67–1.38, p=0.827). While not statistically significant, the improvement in median overall survival is consistent with the improvement in median PFS reported previously. The trial was not designed to detect a statistically significant improvement in overall survival and included a cross-over component. Patients receiving gemcitabine alone who crossed over to receive gemcitabine plus TH-302 upon disease progression did contribute to an increase in survival of the control arm.

TH-302 continues to demonstrate a safety profile consistent with what has been previously reported at the 2012 annual meeting of the American Association of Cancer Research. The most common adverse events were fatigue, nausea, constipation and peripheral edema, and were similar across groups. Skin and mucosal toxicities and myelosuppression were the most common adverse events related to TH-302, were mostly Grade I and II, and did not result in increases in treatment discontinuation. Adverse events leading to discontinuation of study treatment as well as serious adverse events were balanced across all treatment arms. Grade III/IV/V adverse events were generally below 10%.

About Erbitux
Erbitux® is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.

The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.

Erbitux has already obtained market authorization in 92 countries. It has been approved for the treatment of colorectal cancer in 92 countries and for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 89 countries.

Merck licensed the right to market Erbitux outside the US and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone, Bristol-Myers Squibb Company and Merck jointly develop and commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas.

For more information on Erbitux in colorectal and head & neck cancer, please visit: www.globalcancernews.com.

About TH-302
TH-302 is an investigational hypoxia-targeted alkylating agent that is thought to be activated under severe tumor hypoxic conditions, a hallmark of many cancers. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient tumor blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic. TH-302 is currently under evaluation in a Phase III trial in combination with doxorubicin versus doxorubicin alone in patients with soft tissue sarcoma. TH-302 has completed a randomized Phase II trial in combination with gemcitabine versus gemcitabine alone in patients with advanced pancreatic cancer. It is also being investigated in hematological malignancies and in combination trials in solid tumors in Phase I. Merck signed a license and co-development agreement for TH-302 with Threshold Pharmaceuticals Inc.

Phyllis Carter
Phone +49 6151 72-7144

Posted: September 2012


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