Advaxis, Inc., a leader in developing the next generation of immunotherapies for cancer and infectious diseases, has submitted an Application for Orphan Drug Designation with the US Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD) for ADXS-HPV, its lead drug candidate, for the treatment of human papillomavirus (HPV)-associated anal cancer.

Orphan Drug Designation is granted to drug therapies intended to treat diseases or conditions that affect fewer than 200,000 people in the United States. Orphan Drug Designation entitles the sponsor to clinical protocol assistance with the FDA, as well as federal grants, tax credits, and potentially a seven year market exclusivity period.

“The US Centers for Disease Control and Prevention estimates that 85% of the 7,060 new cases of anal cancer projected for 2013 are caused by HPV. The incidence of anal cancer has increased more than twofold from 1975-2009 and is rising,” commented Dr Robert Petit, chief scientific officer of Advaxis. “Despite treatment with surgery, chemotherapy, and radiation, the 5 year survival for patients with lymph node or distant metastases is less than 50%. We hope that ADXS-HPV will improve survival for patients with HPV-associated anal cancer.”

“If granted, Orphan Drug Designation for our lead drug candidate, ADXS-HPV, would provide seven years of market exclusivity for ADXS-HPV, if it is approved by the FDA, tax credits on US clinical trials, eligibility for orphan drug grants, and waiver of the $1.9 million regulatory application filing fee,” commented Thomas A. Moore, chairman and chief executive officer of Advaxis. “We are looking forward to initial data from our Brown University Study in anal cancer that is currently underway.”

ADXS-HPV is an immunotherapy that is designed to target cells expressing the HPV gene E7. Expression of the E7 gene from high-risk HPV variants is responsible for the transformation of infected cells into dysplastic and malignant tissues. Eliminating these cells can eliminate the dysplasia or malignancy. ADXS-HPV is designed to infect antigen-presenting cells and direct them to generate a powerful, cellular immune response to HPV E7. The resulting cytotoxic Tcells infiltrate and attack the tumours while specifically inhibiting tumour Tregs and MDSCs in the tumors that are protecting it.

Anal cancer is a rare malignancy of the gastrointestinal tract, with an estimated 7,060 new cases in the United States in 2013. The most common pathologic type of anal cancer is squamous cell carcinoma (SCCA), which accounts for approximately 85% of all cases. The remaining cases comprise anal adenocarcinoma (10%) and other types (5%). Up to 20% of patients can be asymptomatic at presentation, but most patients present with symptoms related to an anal mass, such as rectal bleeding, perineal pain, the sensation of a mass in the anus, pruritis, and anal discharge. Most patients are diagnosed with localized disease, while approximately 20%-40% of patients present with lymph node involvement, and approximately 10% present with metastatic disease.

Although it is a rare malignancy, the incidence of anal cancer is increasing. From 1973-2000, the incidence of anal cancer in the United States increased by 160% among men and by 78% among women. An estimated 84% of anal carcinomas are caused by HPV; thus, the risk factors for anal cancer are strongly related to sexual practices and behaviours, including number of lifetime sex partners, anal intercourse, and genital warts, all of which reflect an increasing risk of acquiring HPV. The risk of anal cancer is substantially increased in HIV-infected individuals, and an estimated 28% of males with anal cancer during 2001-2005 were HIV-infected.