Big Pharma is also trying to move forward with therapeutic vaccines. MAGE-A3 is currently in Phase III trials for the treatment of melanoma and non-small cell lung cancer (NSCLC) and forms part of GlaxoSmithKline’s antigen-specific cancer immunotherapeutic (ASCI) pipeline. The compound combines purified MAGE-A3 tumor antigen—a protein expressed in a large number of cancers in-licensed from the Ludwig Institute for Cancer Research—with a combination of immunostimulating compounds called AS15. The GSK ASCI pipeline also includes a treatment for acute myelogenous leukaemia at Phase II called WT1 and two other candidates at Phase I, NY-ESO-1 and PRAME.

Beyond vaccine development, GSK has also been working with Abbott Molecular on automated companion diagnostic tests for MAGE-A3 expression since 2009, and in November 2011, expanded the agreement to include the PRAME antigen. The polymerase chain reaction-based tests identify specific DNA sequences to help determine those patients most likely to benefit from the therapy.

Merck Serono is also in the NSCLC space with Stimuvax (BLP25 liposome vaccine), currently in Phase III, which it obtained with worldwide rights for development and commercialization from Oncothyreon. Stimuvax is designed to stimulate the immune system into targeting cells expressing glycoprotein MUC1, which is over-expressed or aberrantly expressed in many types of cancer. NovaRX is another company targeting NSCLC with its lead candidate Lucanix, which is also in Phase III trials that began in 2008. Unlike Stimuvax and MAGE-A3, however, Lucanix is a cell-based therapy that treats patients with four NSCLC cell lines that have been genetically modified to block transforming growth factor-beta. TGF-beta is produced by cancer cells and is thought to exert an immunosuppressive effect thus protecting them from an antitumor response.

NICHE THERAPIES

Although there is much R&D and, more recently, excitement in cancer vaccines, there are many other areas that could potentially benefit from therapeutic vaccines. ImmusanT (Cambridge, MA), for example, has zeroed in on celiac disease and is developing technology based on research performed at The Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, and at the University of Oxford, UK. NexVax2 is a combination of three short peptides from gluten protein that have been shown to cause an immune reaction in the 90% of sufferers with the HLA DQ2 gene, according to company information. NexVax2 is a peptide-based vaccine, but the aim, rather than increasing the immune response, is to desensitize its reaction to gluten. NexVax2 is progressing through to Phase II clinical trials.

The development of therapeutic vaccines as a new approach to combat substance abuse is another potential area for growth. Nicotine and cocaine are both examples of drug targets under development. The concept of long-lasting single injections, for example, removes the hurdle of the reliance on behavioral modification to control the intake of substances with the potential for addiction. Nicotine vaccines are designed to induce production of antibodies that bind to nicotine in the blood creating a molecule that is too large to cross the blood-brain barrier and thus cause pleasurable effect. However, Nabi Biopharmaceuticals announced on Nov. 7, 2011, results from its second Phase III trial for NicVax (Nicotine Conjugate Immunotherapeutic) and, unfortunately, preliminary assessment of the data showed that the primary endpoint was not met and there was no statistical difference between the NicVAX and placebo groups—these results are similar to the first Phase III study. Cytos Biotechnology and Novartis’ collaboration on NIC002, another compound designed to induce nicotine antibodies, also failed to demonstrate efficacy in Phase II trials after interim analysis.

Despite these failures, the market for antismoking products will no doubt continue to drive research into vaccines against nicotine addiction. As with other therapeutic vaccines under development, proving efficacy will remain a key challenge.

REFERENCE

1. BCC Research, Therapeutic Vaccines: The Global Market, Report BIO052B (2010). http://www.bccresearch.com/.