US biotech Antigenics wins Russian approval to market kidney cancer treatment

In a move that will be a fillip to cancer vaccine developers, US biotech Antigenics has won Russian approval to market Oncophage to treat kidney cancer.

It has been a long haul since the discovery in 1991 of the first tumour antigen, coupled with increased understanding of the immune system, inspired attempts to make the body recognise cancer cells as foreign and deal with them accordingly.

Oncophage exemplifies many of the issues that have dogged the progress of cancer vaccines, from the initial hype, to clinical setbacks and investor scepticism. After 11 years in development the product is yet to win approval from the US Food and Drug Administration (FDA) because the data from the Phase III trial, completed in 2006 did not show sufficient efficacy.

But in April, Russian regulators approved the drug on the basis of a subset of that Phase III data, relating to patients with less advanced cancer who mounted a more effective response to the treatment.

The case highlights a huge challenge that most cancer vaccines have yet to overcome.

While vaccines aim to generate an immune response that will make the body’s own defences turn on tumour cells, most cancer patients entering clinical trials are at the advanced stages of disease when the toll of the cancer itself, and the various chemo- and radiotherapy used to treat it, is likely to have damaged their immune systems irreparably.

Of 604 patients in the Oncophage Phase III trial 172 or 28 per cent were treated in Russia. But among all those in the trial who responded to the vaccine, 70 per cent were in this Russian cohort. This persuaded the Russian regulators to accept a filing based on a subset of the trial. According to New York-based Antigenics, this is the first time a drug has been allowed on the market in Russia that was not approved for sale in its home market.

Welcome news

Now Antigenics is setting its sights on Europe, aiming to use the conditional approval process introduced recently by the European Medicines Agency (EMEA), which makes it possible to get permission to market a drug whilst conducting further trials. If these are not successful the product has to be withdrawn.

In the US Antigenics needs to carry out further expensive trials to register Oncophage. So while the Russian approval is a milestone, it does not mean cancer vaccines have established their position in the same way as rival technologies such as monoclonal antibodies.

Nonetheless, the go-ahead will be welcome news for an industry that has suffered a series of setbacks and failures over the past year. In March, the US biotech Genitope axed its product for treating non-Hodgkin’s lymphoma after the Phase III trial showed it had failed to arrest the spread of the disease in patients. Before that, in December 2007, Sanofi-Aventis handed back the rights to Uvidem, a Phase II cancer vaccine designed to treat melanoma, to its developer IDM Pharma of Irvine, California.

One product that has attracted particular attention is Provenge for treating prostate cancer. This was widely expected to be the first vaccine to get approval in the US, but last May the FDA asked the developer Dendreon to supply more data, putting back approval for at least two years. Despite the extra costs it faces as a result of this delay, the Seattle-based firm says it remains committed to making the treatment available as ’rapidly as possible’.

Pharma interest

These late stage failures have undermined the rationale behind products in development, dashed the hopes of patients and frayed the nerves of investor. But just a week before Antigenics won its Russian approval, there was a significant validation for cancer vaccines when Takeda Pharmaceutical, Japan’s largest drug company, signed a $320 million (?160 million) deal with US biotech Cell Genesys for its prostate cancer immunotherapy, GVAX.

Nor is this the first time pharmaceutical companies have ventured into the field. While Sanofi-Aventis may have dropped the IDM product, it made a huge commitment to Oxford Biomedica’s TroVax cancer vaccine when it signed a licensing deal worth 518 million euros (?416 million) in March 2007.

Currently in Phase III trials for the treatment of renal cancer, it is hoped that TroVax will prove to be effective against a wide range of other cancers. One of the most impressive aspects of trials to date is that more than 90 per cent of patients mounted an immune response.

The market analysts Arrowhead forecast the worldwide market for cancer vaccines will reach $6 billion by 2010. But to date the biggest commercial success has come not in therapeutic vaccines, but preventative ones. There are currently two registered products, Gardasil, developed by Merck, for the prevention of cervical cancer, and Hepatitis B for preventing liver cancer.

Nuala Moran