ISA Pharmaceuticals Initiates Phase I/II Clinical Trial of ISA101 in Patients with Anal Intraepithelial Neoplasia (AIN)

ISA Pharmaceuticals B.V., a clinical-stage biopharmaceutical company focusing on rationally designed, fully synthetic therapeutic vaccines against cancer and persistent viral infections, has announced the initiation of a Phase I/II clinical study of its lead candidate ISA101 in HIV-positive men suffering from anal intraepithelial neoplasia (AIN). The study is supported by ZonMw, the Dutch Organisation for Health Research and Development, and is being conducted in The Netherlands.

ISA101 is a synthetic long peptide (SLP®) vaccine for the treatment of diseases induced by human papilloma virus type 16 (HPV16), such as cervical cancer, ano-genital premalignant and malignant lesions, and head and neck cancer.

The open-label, dose-response study will be conducted in 30 HIV-positive male patients suffering from HPV16-positive high-grade AIN, who failed previous treatment. In the first dose escalation part of the trial, patients will be vaccinated with ISA101 in three dosing cohorts three times at three-week intervals, either with or without administration of peg-interferon-α on the day of vaccination. An additional group of 15 patients will be treated with the optimal ISA101 schedule. Primary clinical endpoints will be toxicity and safety as well as regression of lesions at 3, 6 and 12 months Secondary endpoints are regression of lesions at 18 months and HPV16-specific immunity in the blood.

AIN is caused by infection with high-risk papilloma viruses (HPV) and known as a cancer precursor lesion that can lead to the development of anal cancer. AIN of any grade has been reported to be present in 63–81% of HIV-positive men, and high-grade disease (AIN 2 or 3) in 25–52%. The majority (approximately 60%) of high-grade AIN is caused by HPV16. Incidence of anal cancer has increased significantly since 1997 in both men and women, and especially in HIV-positive men. This is assumed to be a result of the significantly prolonged life span of HIV-positive patients. Therefore, early diagnosis and treatment of AIN is important to prevent malignancy. At present, there is no systemic treatment.

“This trial is part of our strategy to demonstrate that ISA101 is ideally suited to combat diseases caused by HPV16, a virus associated with several cancers and precancerous lesions,” said Jan Fagerberg, CMO of ISA Pharmaceuticals. “It is the first of two clinical trials of our lead product that we are initiating this year. The current trial will also specifically assess a novel, standardized intradermal injection route together with interferon-α administration. We expect first results from this trial in 2014.”