Advaxis (NASDAQ:ADXS) hopes to begin a registration trial before the end of the year with its next-generation immunotherapy, ADXS-HPV, for the treatment of invasive cervical cancer.
“We are pleased with the encouraging results of our Phase 2 study, which supports a continuing path towards registration for our lead product candidate,” CEO Daniel O’Connor says in an interview with BioTuesdays.com.
“The completion of the study is a considerable step forward in demonstrating the potential of our technology to have a positive impact on an unmet medical need,” he adds.
The company hopes to have an end-of-Phase 2 meeting with the FDA in the first half this year to finalize the Phase 3 protocols and submit a special protocol assessment to the agency.
Advaxis immunotherapies are based on a novel platform technology which uses live, attenuated bacteria that are bio-engineered to secrete antigen/adjuvant fusion proteins designed to redirect, to the cancer itself, the powerful immune response that individuals have to the bacterium.
Citing four essential steps of cancer immunotherapy, Mr. O’Connor contends that Advaxis possesses the only technology that integrates all of these elements into a “single, well-tolerated, low-cost-to-manufacture and easy-to-administer immunotherapy.”
Human papillomavirus (HPV) is believed to cause 99% of cervical cancers. The malignancy is highly aggressive and has a poor prognosis, and there is no standard of care.
To date, Advaxis has administered more than 500 doses of its lead product to 200 patients. According to Mr. O’Connor, ADXS-HPV has demonstrated improved survival, complete and partial responses, alone or in combination with chemotherapy in recurrent cervical cancer.
In a Phase 2 clinical trial conducted in India with 110 patients, of which 55 received ADXS-HPV only and 55 received ADXS-HPV plus the chemotherapy drug, cisplatin, 58% of patients reported no adverse events. Patients who experienced low grade, cytokine-release syndrome responded to treatment or self-resolved.
Overall, the 12-month survival rate in the trial was 36%, and the 18-month survival was 28%.
Mr. O’Connor says the company’s registration program includes two Phase 3 multinational trials with partner participation. “We have no competition in late-stage cervical cancer.”
According to the WHO, there are 527,000 new cases of cervical cancer worldwide annually. Current vaccines prevent infection by two, of the15, high-risk HPV strains, but have no effect on millions of people already infected.
Advaxis also is evaluating ADXS-HPV in other HPV-associated cancers, including in a Phase 2 trial in advanced cervical cancer, a Phase 1/2 study in head and neck cancer, and a Phase 1/2 trial in anal cancer.
ADXS-HPV has orphan drug status from the FDA for both anal and head and neck cancers. There are some 99,000 new cases of anal cancer and 80,000 new cases of head and neck cancer worldwide annually.
Mr. O’Connor says Advaxis plans to retain the U.S. rights to ADXS-HPV and license its lead product on a regional basis outside of the U.S.
In December, Advaxis inked a licensing agreement with Global BioPharma, a Taiwan-based biotech company, formed solely to develop and commercialize ADXS-HPV for the treatment of HPV-associated cancers in Asia. Global BioPharma is funded by a group of investors led by Taiwan Biotech.
Mr. O’Connor says Global BioPharma plans to conduct registration trials with ADXS-HPV for the treatment of advanced cervical cancer and will explore the use of Advaxis’ lead product candidate in several other indications, including lung, head and neck, and anal cancers. Its territory covers more than four billion people, with over 200,000 annual diagnoses of cervical cancer, accounting for roughly 40% of the world’s cases.
“Funded by one of the largest Taiwanese pharmaceutical companies, this deal further validates Advaxis’ proprietary immunotherapy technology,” he points out.
Advaxis has created more than 15 distinct immunotherapies based on its platform. ADXS-cHER2 is an immunotherapy for the treatment of HER2 overexpressing cancers, such as breast, gastric, esophageal and other cancers in humans and for osteosarcoma in canines.
In animal health, ADXS-cHER2 has demonstrated encouraging survival data in a Phase 1 trial in canine osteosarcoma. The company is considering future expansion into canine T-cell and B-cell lymphoma, which has five million new cases a year in the U.S. and affects one-in-15 dogs.
“The Phase 1 data provide the rationale to advance this same immunotherapy into a Phase 1 clinical trial in women with HER2-positive breast cancer,” Mr. O’Connor says. The company is preparing an investigational new drug submission for ADXS-cHER2 in breast cancer and hopes to begin Phase 1 testing in 2014.
Advaxis also is developing ADXS-PSA for the treatment of prostate cancer and hopes to initiate a Phase 1 study in 2014. “We expect ADXS-PSA to have a similar safety profile to that of ADXS-HPV which, along with ADXS-cHER2, represent potential partnering opportunities for us,” he adds.