August 25, 2016 Vaccibody announces positive results from the phase I part of the clinical trial VB C-01 in patients with high-grade cervical dysplasia and recommendation by the cohort review committee as well as the independent data monitoring board to continue to the expansion phase (IIa)
Vaccibody AS today announced that the cohort review committee as well as the independent data monitoring board have completed their review of the interim analysis of the results from the phase I dosing part of the multicentre trial VB C-01. The two committees recommended continuation of the trial into the expansion phase IIa.
VB C-01 is an exploratory, open-label, multicenter phase I/IIa study of VB10.16 immunotherapy for the treatment of high grade Cervical Intraepithelial Neoplasia (CIN 2/3) caused by human papillomavirus 16 (HPV16).
The phase I enrolled patients in two cohorts of eight patients each receiving three doses of 3 mg of VB10.16 either at week 0, 3 and 6 (Cohort 1) or week 0, 4 and 12 (Cohort 2). The primary objective of the study is to evaluate the safety and tolerability of three doses of 3 mg VB10.16. The secondary objectives are to assess T cell mediated immune responses in the peripheral blood and to evaluate early signs of efficacy by means of HPV clearance and CIN regression. The vaccine is delivered with a needle-free, pain-less PharmaJet® Stratis Needle-free Injection System.
The treatment with VB10.16 was well tolerated. No serious adverse advents (SAEs) have been reported. The most common AEs were transient mild to moderate local site reactions at the administration site.
Immunological analyses of the peripheral blood demonstrated a strong induction of HPV16-specific T cell immune responses in twelve of fourteen patients (86%) evaluated to date. The response was induced against both antigens used in the vaccine (HPV16 E6 and E7). The short interval immunization regimen in Cohort 1 induced a more rapid, stronger and longer-lasting T cell response than seen with the schedule with longer intervals used in Cohort 2.
The clinical data further supports selection of Cohort 1 for the upcoming phase IIa expansion phase. In this Cohort histopathological regression to low grade neoplasia (CIN 1) or no disease in 50 % (4 of 8) of the patients already after 4 months was observed. In patients followed for 6 months so far, 75 % (3 of 4) show regression to CIN 1 or no disease. The strength of the immune response correlates with reduction in the size of the lesions and shows a clear trend with CIN regression, HPV regression as well as HPV16 clearance already at this early stage. Vaccibody will enroll 15-20 additional patients with CIN 2/3 in the expansion phase using the shorter vaccination intervals.
Martin Bonde, CEO of Vaccibody, commented: We are very pleased with the promising data we have seen so far. Not only does the vaccine appear to have an excellent safety profile, but also the T cell immune responses observed to date indicate that VB10.16 induces the strongest HPV16-specific immune response we have seen reported in the literature. While other DNA vaccines developed for this indication require delivery with in vivo electroporation, which is quite painful for the patients, VB10.16 is delivered by a simple needle-free, painless jet injection which we believe improves patient compliance tremendously and will be a significant asset in further development of this product. The fact that we already at 4 and 6 months see CIN regression in a high percentage of these patients and see trends to correlate this with the vaccine-induced immune responses, is highly encouraging, even if the number of patients evaluated is still low. We look forward to further substantiate the efficacy of VB10.16 in the upcoming phase IIa study.
This is the first clinical study utilizing Vaccibody’s Vaccine Platform Technology and the positive results can have a significant impact not only on the development of the company’s lead product, VB10.16, but also represent a proof of principle for the technology and the potential to use this platform in further indications.
Coordinating investigator, Prof. Dr. med. Peter Hillemanns, Director of the Department of Gynaecology and Obstetrics at the Hannover Medical School (Germany) commented: We were excited to see the data of the interim analysis for patients with CIN 2. It was striking to see the importance of a rapid vaccination regime which clearly showed and early onset of a strong CD8 T cell response in a very high percentage of patients, which seems to translate into a clinical response already after a very short period in several patients. Our hope is that we will be able to develop a non-invasive treatment option for this precancerous condition to prevent progression to cancer.
The company’s lead product, VB10.16, is a therapeutic DNA vaccine developed to treat human papillomavirus type 16 (HPV16) induced pre-malignancies and malignancies.
About Cervical Intraepithelial Neoplasia (CIN) and Cervical Cancer
Per year approximately 530,000 women are diagnosed with cervical cancer worldwide and over 275,000 women die of the disease annually. Invasive cervical cancer is preceded by a long phase of pre-invasive disease called Cervical Intraepithelial Neoplasia (CIN). Globally the number of high grade lesions (CIN 2/3), the immediate precursors to malignancy, is estimated to be in the range of 10 million.
Virtually all cervical cancers are caused by high risk HPV types. Among the different high risk HPV types known, HPV16 has been reported to be the most common genotype in high grade cervical intraepithelial neoplasia. It can be detected in up to 60 % of all cervical cancers, especially in younger women and it has also been found to play an essential role in the development of several other cancer types (approximately 90% of anal cancers; 40% of penile, vaginal, and vulvar cancers; 25% of oral cavity cancers and 35% of oropharyngeal cancers).
Current standard therapy for CIN 2/3 varies between countries and regions and often involves surgical removal of the affected tissue. These invasive procedures are associated with bleeding, infection, cervical stenosis, scarring and most importantly pre-term deliveries in subsequent pregnancies. As a result, there is a significant need for an effective therapeutic vaccine to treat existing HPV infection and associated pre-malignancies and malignancies of the cervix and thereby prevent the development of cervical cancer caused by human papillomavirus.
About Vaccibody AS
Vaccibody is a biopharmaceutical company dedicated to the discovery and development of novel immunotherapies. Vaccibody’s lead program is focused on VB10.16, a therapeutic DNA vaccine against HPV16 induced pre-malignancies and malignancies. The first-in-human study will evaluate the safety and immunogenicity of VB10.16 in women with high grade cervical intraepithelial neoplasia (HSIL; CIN 2/3).