Vical Incorporated announced that the company has completed enrolment of the planned 375 subjects in its multinational phase 3 trial of Allovectin-7 in patients with metastatic melanoma. Allovectin-7 is a novel gene-based immunotherapeutic with a unique mechanism of action that is fundamentally different from currently approved treatments, and has the potential to be the first new primary treatment approved for metastatic melanoma in nearly 20 years.
“We are pleased to complete enrolment in this pivotal Phase 3 Allovectin-7 trial,” said Vijay Samant, Vical’s president and chief executive officer. “We focused our recruitment efforts in North America, major European countries, Israel and Brazil, paving the path toward approvals in these key melanoma markets. Through the Special Protocol Assessment (SPA) process with the FDA, we designed our trial to demonstrate the advantages of our approach and improve the probability of success in achieving our primary endpoint of overall response rate."
“Immunotherapy takes longer than chemotherapy to begin working,” added Samant, “but responses typically last longer as well. We believe our primary trial endpoint -- comparing response rates after at least 6 months of treatment -- captures the long-term benefit of Allovectin-7 over chemotherapy. We designed our trial to include patients most likely to benefit from our treatment, and specifically excluded patients with brain or liver metastases, patients previously treated with chemotherapy, and patients with elevated LDH levels. Our trial allows physicians to keep treating patients through at least two treatment cycles -- long enough for our immunotherapy to start working.”
Allovectin-7’s safety profile is excellent -- with no drug-related serious adverse events reported to date in the phase 3 trial. Three independent Safety Monitoring Board reviews revealed no safety concerns and support continuation of the current trial.
Vical is conducting the AIMM (Allovectin-7 Immunotherapeutic for Metastatic Melanoma) trial, a phase 3 pivotal trial of the company’s Allovectin-7 cancer immunotherapeutic as first-line therapy in approximately 375 patients with Stage III or IV recurrent metastatic melanoma in accordance with a SPA agreement completed with the US Food and Drug Administration (FDA). Patients may have been previously treated with surgery, adjuvant therapy, and/or biotherapy, but cannot have been previously treated with chemotherapy. The patients were randomized on a 2:1 basis: approximately 250 patients for treatment with Allovectin-7 and approximately 125 for treatment with their physician’s choice of either of two chemotherapy agents, dacarbazine or temozolomide. The primary endpoint is a comparison of overall response rates at 24 weeks or more after randomization. The study will also evaluate safety and tolerability as well as survival.
Under a previously announced collaborative agreement, AnGes MG, Inc., is funding the AIMM trial through a series of cash payments and equity investments. Vical has received the full $22.6 million committed by AnGes. In exchange for funding the trial, AnGes received exclusive marketing rights in Japan and other key Asian countries, and Vical is obligated to pay AnGes tiered royalties based on defined sales levels in the United States, and fixed royalties on rest-of-world sales. AnGes is obligated to pay Vical royalties on product sales in the specified Asian countries, plus certain sales-based milestone payments if defined sales levels are achieved. Each company will be responsible for obtaining regulatory approvals in any countries where it plans to market Allovectin-7.
Allovectin-7 is a plasmid/lipid formulation containing the DNA sequencesencoding HLA-B7 and beta-2 microglobulin, which together form a Major Histocompatibility Complex Class I antigen. Injection of Allovectin-7 directly into tumours is designed to stimulate an immune response against both local and distant metastatic tumours.
Vical estimates that the worldwide market for Allovectin-7 as a treatment for metastatic melanoma could exceed $500 million annually, and applications for other types of cancer could further expand its total use. Because the mechanism of action for Allovectin-7 is not melanoma-specific, it has the potential to be used in any solid tumours. AnGes’ interest in Allovectin-7 is driven by evidence of its activity in previous phase 1/2 U.S. trials in head and neck cancer, which is far more prevalent than melanoma in Asia. Vical has produced all clinical lots used in the development of Allovectin-7, and the company’s existing cGMP manufacturing facility has the capacity to meet anticipated commercial needs for several years after initial product launch.
Allovectin-7 has been granted orphan drug designation for the treatment of invasive and metastatic melanoma by the FDA’s Office of Orphan Products Development. Orphan drug designation provides US marketing exclusivity for seven years if marketing approval is received from the FDA, in addition to certain tax benefits for qualifying expenses.
Vical researches and develops biopharmaceutical products based on its patented DNA delivery technologies for the prevention and treatment of serious or life-threatening diseases.