FDA Grants Orphan Drug Status to Amatuximab for Malignant Pleural Mesothelioma

Mesothelioma in a core biopsy

Amatuximab has received orphan drug status from the FDA to treat patients with malignant pleural mesothelioma, the most common form of mesothelioma.

Amatuximab (MORAb-009) is a monoclonal antibody designed to target mesothelin, a cell surface glycoprotein associated with cell adhesion that is overexpressed in certain types of cancer, including pancreatic ductal adenocarcinoma, mesothelioma, epithelial ovarian cancer, and lung adenocarcinoma.

New therapeutic agents such as amatuximab are given orphan status when they treat a disease that affects fewer than 200,000 patients in the United States. About 3,000 new cases of mesothelioma are diagnosed nationally each year, according to the American Cancer Society. Between 2000 and 2008, the 5-year survival rate for patients with malignant mesothelioma was 7.0%, according to the most recent data from the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) Program.

“We are very pleased to receive orphan drug designation for amatuximab for the potential treatment of malignant pleural mesothelioma,” said Julia Maltzman, MD, Senior Director of Clinical Development at Morphotek Inc., a subsidiary of amatuximab manufacturer Eisai Inc., in a statement. “Ultimately, this antibody has the potential to provide an additional treatment option for patients suffering from an extremely serious disease.”

Results of a multicenter phase II clinical trial of amatuximab in combination with a chemotherapy regimen of pemetrexed and cisplatin were presented at the American Society of Clinical Oncology (ASCO) meeting earlier this year. The study enrolled 89 patients with malignant mesothelioma who received amatuximab 5 mg/kg on days 1 and 8 with pemetrexed 500 mg/m² and cisplatin 75 mg/m² (PC) given on day 1 of each 21-day cycle for 6 cycles. Patients who achieved an objective response or stable disease received amatuximab alone until the disease progressed. The efficacy data was compiled using results from the first 77 patients who had at least 1 post-baseline imaging assessment or who died. The primary endpoint of the study was progression-free survival (PFS), with overall survival (OS), objective response rate, and safety serving as secondary endpoints.

According to an independent radiological review, 30 (39%) of patients achieved a partial response and 39 (51%) had stable disease. After 6 months, PFS was 52% (95% confidence interval [CI], 39.5—63.5) with a median PFS of 6.1 months (95% CI, 5.4–6.5). The median OS was 14.5 months (95% CI, 12.4–18.5), although updated results presented at ASCO showed a median OS of 14.8 months. As of April, 29 patients were still alive, and 5 of those patients were continuing to receive amatuximab as maintenance therapy. In addition to the expected toxicity from the PC chemotherapy regimen, 12.4% of patients experienced hypersensitivity reactions due to amatuximab, with 4.5% of patients experiencing grade 3 or 4 hypersensitivity reactions.

The researchers noted that PFS was not significantly different from what is observed with the PC chemotherapy regimen alone. However, the OS benefit observed in the study was considered a benefit. The researchers suggested that the efficacy of amatuximab in this population should be studied in a more stringent randomized trial. Additionally, the researchers identified megakaryocyte potentiating factor (MPF) as a potential biomarker for response.

Hassan R, Jahan TM, Kindler HL, et al. Amatuximab, a chimeric monoclonal antibody to mesothelin, in combination with pemetrexed and cisplatin in patients with unresectable pleural mesothelioma: results of a multicenter phase II clinical trial. J Clin Oncol. 2012;30(suppl; abstr 7030).