On September 2, 2014 Amgen reported the submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) via the centralized procedure for talimogene laherparepvec seeking approval for the treatment of adults with melanoma that is regionally or distantly metastatic (Press release Amgen, SEP 2, 2014, View Source [SID:1234500719]). Talimogene laherparepvec is an investigational oncolytic immunotherapy administered as an intralesional injection that is designed to initiate a systemic anti-tumor immune response. If approved, talimogene laherparepvec will represent the first in a class of novel agents known as oncolytic immunotherapies.

The MAA for talimogene laherparepvec contains data from more than 400 patients and is based on a global, randomized, open-label Phase 3 trial evaluating the safety and efficacy of talimogene laherparepvec in patients with stage IIIB, IIIC or IV melanoma when resection was not recommended compared to granulocyte-macrophage colony-stimulating factor (GM-CSF).

“The submission of the Marketing Authorization Application in Europe for talimogene laherparepvec brings us a step closer to helping address an unmet medical need for patients with metastatic melanoma,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “This regulatory milestone, on the heels of our Biologics License Application submission to the U.S. FDA, represents an important step for our pipeline and we look forward to working with the European Medicines Agency as it conducts its review of talimogene laherparepvec.”

Melanoma is a type of skin cancer that is characterized by the uncontrolled growth of melanocytes, which are the cells responsible for providing the pigment to skin. Melanoma is the most aggressive and serious form of skin cancer. Currently, 132,000 melanoma cases occur globally each year. The number of people with melanoma is expected to rise considerably worldwide, with more than 279,000 projected new cases by the year 2020.3 Outcomes are substantially worse for people with regional and distantly metastatic disease, with high risk of recurrence for Stage IIIB, IIIC, and IV melanoma.

Melanoma is considered to be advanced when it has spread, or metastasized, from the origin site to deeper parts of the skin or other organs such as the lymph nodes, lungs or other parts of the body distant from the primary tumor site.

On September 1, 2014 Exelixis reported top-line results from the final analysis of COMET-1 (NCT01605227), the phase 3 pivotal trial of cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed after treatment with docetaxel as well as abiraterone and/or enzalutamide (Press release Exelixis, SEP 1, 2014, View Source [SID:1234500718]). The trial did not meet its primary endpoint of demonstrating a statistically significant increase in overall survival (OS) for patients treated with cabozantinib as compared to prednisone. The median OS for the cabozantinib arm of the trial was 11.0 months versus 9.8 months for the prednisone arm (hazard ratio 0.90; 95% confidence interval 0.76 – 1.06; p value 0.212).

The COMET-1 results are the subject of ongoing analyses. Exelixis will submit additional data, including secondary and exploratory endpoints, for presentation at a future medical conference. Besides OS, the exploratory endpoint of progression-free survival (PFS) as assessed by the investigators is the only time-to-event-based endpoint for which data are available. Median PFS was 5.5 months for the cabozantinib arm of the trial versus 2.8 months for the prednisone arm (hazard ratio 0.50; 95% confidence interval 0.42 – 0.60; p value <0.0001). Safety data were consistent with those observed in earlier-stage trials of cabozantinib in mCRPC. As a result of the outcome of COMET-1, Exelixis will initiate a significant workforce reduction to enable the company to focus its financial resources on the late-stage clinical trials of cabozantinib in metastatic renal cell carcinoma (the METEOR trial) and advanced hepatocellular carcinoma (the CELESTIAL trial). The company will reduce its workforce by approximately 70 percent, or approximately 160 employees, resulting in approximately 70 remaining employees. Exelixis anticipates the one-time restructuring charge associated with the workforce reduction to be approximately $6 million - $8 million, with the majority to be completed by the end of the fourth quarter of 2014. As a result of this and other cost-saving measures contemplated, the company anticipates that it has sufficient cash to support its operations through the release of top-line results of the METEOR trial next year. More financial details will be provided by the company in its third quarter 2014 financial report. "We are very disappointed that COMET-1 did not meet its primary endpoint of extending overall survival in men with mCRPC," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "We are grateful to the patients, physicians, nurses, caregivers, and other study team members who participated in the trial. We remain focused on the development program for cabozantinib beyond mCRPC, including the ongoing METEOR and CELESTIAL phase 3 pivotal trials, from which we expect top-line data in 2015 and 2017, respectively." Dr. Morrissey continued, "We have thoughtfully prepared for this scenario and the resulting very difficult decisions. The workforce reduction we have announced today is necessary to significantly reduce our corporate operating expenses. I would like to personally express my deep appreciation to the talented and dedicated Exelixis employees who will be impacted by these actions, both for their commitment to Exelixis and for their tremendous contributions to patients with cancer." Based on the outcome of COMET-1, Exelixis has deprioritized the clinical development of cabozantinib in mCRPC. Enrollment in COMET-2, which is the second pivotal trial in mCRPC and evaluates pain palliation, has been halted. The company expects top-line data before the end of this year. Based on the outcome of COMET-2, Exelixis will discuss with regulatory authorities the potential regulatory path, if any, of cabozantinib in mCRPC. Other company-sponsored studies in mCRPC, including a randomized phase 2 study of cabozantinib in combination with abiraterone, will also be halted.