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PRODUCT DESCRIPTION
Hi-8 MEL is Oxford BioMedica’s therapeutic vaccine for metastatic melanoma. The product consists of two recombinant vectors, a plasmid DNA and a non-replicating Modified Vaccinia Ankara (MVA) virus. Both vectors encode the Mel3 polyepitope string derived from five different melanoma-associated antigens. Administration of the two recombinant vectors in a heterologous prime-boost format is designed to induce broad melanoma-specific CD8+ T-cell responses.
INDICATION
Metastatic melanoma.
MARKET
Melanoma comprises just 5% of all skin cancers but it is the most deadly. It is the seventh most common cancer in the USA. In 2006, more than 100,000 cases of the disease were estimated to be diagnosed with melanoma in the seven major pharmaceutical markets. High unmet needs still persist for this tumour type. Median survival is less than one year for Stage IV disease and less than five years for Stage III disease. The total treatment market for melanoma is forecast to be in excess of US$775 million by 2010 (Datamonitor). Melanoma is increasing in incidence by more than 4% per year and its prevalence has doubled in the last 20 years. Existing treatments for Stage III/IV metastatic melanoma offer limited efficacy and often have serious side-effects.
TECHNICAL DESIGN
Hi-8 MEL is designed using the proprietary Hi-8 Prime-Boost technology platform. Its two vectors are administered in a heterologous prime-boost sequence. The DNA is administered by intramuscular injection followed by an MVA boost administered by intradermal injection. This allows the presentation of disease-specific antigens to the body, inducing an initial T-cell response. The second application amplifies and reinforces the T-cell response, arming the body to destroy diseased cells and suppressing tumour growth.
Vaccinia viruses are widely used as delivery systems for antigen-specific vaccines. MVA is the vaccinia virus strain of choice because of its excellent safety profile and its effectiveness in stimulating an immune response.
CLINICAL STATUS
Completed Phase I study - Phase I study in 14 HLA-A2 positive Stage II/III/IV metastatic melanoma patients with no evidence of disease. Hi-8 MEL was well tolerated in all patients.
- Immunological melanoma-specific CD8+ T-cell responses were seen in 50% of patients.
Completed Phase II study
- Phase II dose-selection study in 41 HLA-A2 positive patients with non-resectable, stage III/IV melanoma.
- All clinical endpoints were achieved, demonstrating that Hi-8 MEL was well tolerated at all doses and showed clinical benefit.
- Immunological melanoma-specific CD8+ T-cell responses were seen in 91% of patients receiving the highest dose.
- Tumour responses were seen in nearly 20% of patients (eight patients). One partial response was observed (with a 51% reduction in target lesions) which was durable at 108 weeks follow up. This patient received additional Hi-8 MEL booster immunisations for a two-year period.
- All but one of the patients who showed periods of disease control had associated immune responses.
Median time to progression was 16 weeks for immune responders versus eight weeks for non responders (p<0.05).
- Median survival was 100 weeks for immune responders versus 37 weeks for non-responders (p<0.001) and 42 weeks for a group of control non-HLA A2 patients who received standard of care, after 24 months follow-up.
DEVELOPMENT AND COMMERCIALISATION STRATEGY
Commercial partners sought to co-develop and market the product.
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