Industry Trend Analysis - Cancer Vaccines Remain Viable Immuno-Oncology Target - AUG 2017

BMI View: Positive results for a cancer vaccine highlight that this segment of immuno-oncology is still viable. Vaxon Biotech is taking a non-personalised approach, which will limit manufacturing costs, and aid in capturing market share if it gains approval. The small biotech will attract the interest of larger firms, either through development agreements or financing.

Cancer vaccines have had a chequered past with a number of candidates failing at mid and late stages of development. High-profile failures in the development of cancer vaccines include GlaxoSmithKline and Merck KGaA, which have both abandoned candidates. Even successful candidates such as Sanpower's Provenge, have experienced post-marketing problems due to the high cost and complexity of manufacturing. This has dampened the excitement around these novel candidates, with other immuno-oncology products gaining the majority of development focus. However, there are still companies attempting to create a success in cancer vaccines.

Vaxon Emerges As A Potential Success

Vaxon Biotech, a biopharmaceutical company developing therapeutic cancer vaccines based on optimised cryptic peptides, has announced the results of its Phase IIb trial of Vx-001 in non-small cell lung cancer (NSCLC).

Vaxon launched the Phase IIb trial in August 2011 in 70 European trial centres. It evaluated 190 patients with metastatic and distant recurrent NSCLC, who experienced disease control after platinum-based first-line chemotherapy. Key inclusion criteria included patients being HLA-A2-positive and their tumours expressing TERT, the antigen targeted by Vx-001. The study was a double-blind, placebo-controlled trial with 101 placebo and 89 Vx-001-treated patients. The primary endpoint was overall survival, with the secondary endpoints of time-to-treatment failure and 12-month overall survival rates.

Vx-001 was shown to be highly efficacious in a specific sub-group of patients who had never smoked or were light smokers (defined as having smoked for less than 20 years) with non-immunogenic tumours (defined based on a proprietary diagnostic biomarker test). In this defined patient subgroup there was a statistically significant increase in overall survival: 20.2 months versus 7.9 months in the placebo group (p=0.0001). The time-to-treatment failure rate also increased to 5.6 months, against 3.3 months in the placebo group (p=0.005). Moreover, the 12-month survival increased to 80% against 8% in the placebo group (p=0.0003).

Furthermore, due to the increasing prevalence of immune checkpoint inhibitors as second- and third-line treatments, the study did provide data as a surrogate combination study giving a signal for higher incremental survival for checkpoint inhibitor treated patients with Vx-001 compared with placebo. These data suggest that Vx-001 has the potential to turn cold tumours hot in order to leverage effectively the natural immune system in response to certain tumour sub-types.

Vaxon's optimised cryptic peptides, like neo-antigen vaccines, avoid the problem of immune tolerance and are strongly immunogenic. Unlike neo-antigen vaccines, the company's optimised cryptic peptides do not need to be personalised; instead they have the potential to treat tumours across a broad range of patients, since optimised cryptic peptides are essentially 'universal neo-antigens'. The lack of a personalisation requirement could reduce the manufacturing complications associated with other cancer vaccines in development, and provide a competitive edge for Vaxon. However, the company is small and further behind in development compared with the firms at the forefront of cancer vaccine R&D. Despite Vaxon lagging behind, these results and the potential to be used in combination with checkpoint inhibitors will serve to attract interest in the company, and development agreements or investments could follow. Of note, Vaxon's product could still fail in trials, as late-stage failures are common in the cancer vaccine market.

Vaxon is finalising the design of a confirmatory trial to explore the subgroup results indicated in the Phase IIb trial. The defined patient group is expected to be an HLA-A2 positive, negative for EGFr and ALK mutations, never or light-smoking NSCLC population with no natural immunity in NSCLC Stage IV after four cycles of platinum-based chemotherapy. It is estimated that this target population would represent globally around 22,000 new patients per year.

Secondary Generation Vaccines Will See More Success

Interdisciplinary advances are driving a new wave of cancer vaccines with greater potential for success. Specialised firms will continue to capitalise on big pharma's rising interest though deal-making activities, and the wider investment community. These next-generation cancer vaccines will achieve better results, and manufacturing methods and costs will be addressed, which will aid commercial success.

Bristol-Myers Squibb is developing Prostvac (rilimogene galvacirepvec/rilimogene glafolivec), Bavarian Nordic's investigational prostate-specific antigen-targeting cancer immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. It is currently in Phase III trials with results due by the end of 2017, and it is likely that BMS will be able to bring this vaccine to market and see success.