Vaccine for Papilloma Virus Shows Promise

A phase II trial of a new vaccine candidate for patients with human papilloma virus (HPV)-related disease has shown partial clinical and/or histologic responses, associated in some cases with viral clearance, in five of 15 patients treated with a high dose of the vaccine.

HPV is the most common sexually transmitted disease, infecting perhaps 300 million women worldwide. More than half of all cervical cancers are caused by HPV type 16, one of the high-risk HPV types (HR-HPV). Most patients spontaneously eliminate the infection within six to 12 months, but those who do not will develop long-lasting HR-HPV and are at greatest risk of developing cervical cancer.

In countries with screening programs, the cancer risk is reduced because precancerous, asymptomatic lesions such as high-grade cervical intraepithelial neoplasia (CIN2/3) are detected and excised by a surgical procedure called conisation. The progression from HPV infection to cervical cancer takes several years, providing a strong rationale for developing a therapeutic vaccine for silent, persistent HPV infections and CIN2/3 lesions.

It is estimated that more than one million women in Europe have long-lasting HPV infection that they could not eliminate within six to 12 months and therefore are at a higher risk of suffering from CIN2/3 and later from cancer. An effective vaccine could prevent the occurrence of cervical dysplasia in this population.

The clinical trial, involving up to 28 women with CIN2/3, has been ongoing in France with the new vaccine, called MVA-HPV-IL2. The patients are divided into two groups for the evaluation of two different doses administered subcutaneously. Patients are treated with the vaccine on days 1, 8, and 15, with conisation performed at week six. The trial's primary objective is to demonstrate clinical and histologic efficacy as measured by the elimination of the CIN lesions at six weeks.

"Our approach is consistent with the recommendations of prominent HPV and cancer researchers worldwide who have called for developing a therapeutic agent to prevent progression through the various stages of HPV-related disease,” said Patrick Squiban, M.D., vice president, regulatory and medical affairs, Transgene (Strasbourg, France; www.transgene.fr), the developer of the vaccine.

In addition to the clinical and histologic responses, an analysis performed on 27 evaluable patients confirmed excellent tolerance of the vaccine. No indication of CIN regression was observed in the 12 patients treated with the low dose. A new trial is being submitted to test the highest dose and postpone surgery for up to six months after administration.

"We believe that conducting a trial focused on the highest dose of MVA-HPV-IL2 and delayed surgery is the right step toward achieving that goal,” explained Dr. Squiban.

The vaccine was simultaneously tested in 20 patients with vulvar intra-ephithelial neoplasia (VIN3). Clinical results showed no significant difference in the patients treated with the vaccine, compared to the placebo group. In view of the dose-related effect seen in the CIN2/3 trial, these results were probably due to the low dose used and the advanced stage of the patients.




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