US biotech Antigenics has won approval for its kidney cancer vaccine Oncophage in Russia and expects to bring it to market in the second half of 2008.

The registration marks a turnaround for Oncophage (vitespen), which was knocked back in the USA after the top-line data from a Phase III study in renal cell carcinoma failed to show a benefit for the vaccine. The vaccine is made from each patient’s own kidney cancer tissue at Antigenics’ facility in the USA, so is an ultimate expression of the trend towards ‘personalised medicine’ in the drug industry.

Although Antigenics was able to show that Oncophage boosted recurrence-free survival by 45% in a subset of intermediate-risk patients – a group which crucially could be well-defined using kidney cancer staging criteria – the trial as a whole did not reach statistical significance.

As a result the US Food and Drug Administration (FDA) was unable to accept the findings, mainly because of its policy on statistical analysis that demanded the whole patient population be considered.

Antigenics’ response has been to develop Oncophage elsewhere, and it hopes approval in Russia could act as a springboard for a subsequent roll-out of the product across Europe. In the EU there is a possibility it could win a conditional market authorisation, based on the subset analysis, albeit with the likelihood that a second trial would be required in parallel with its launch onto the market.

But in the meantime, “Russia is a key market for Oncophage, and accounted for around 25% of the total number of patients enrolled in Antigenics’ Phase III study,” said Garo Armen, the company’s CEO, in an interview.

Oncophage was filed in Russia last June, and the government’s advisory board – the Pharmacology Committee – met and approved the application earlier this year. Now, the formal registration certificate has been issued for use of the vaccine in the treatment of patients with intermediate risk of disease recurrence.

“We have found there is less bureaucracy in Russia, but its still a rigorous process. One difference is that you get almost continuous dialogue – you don’t get into a situation with formal letter writing and responses within 30 or 60 days,” according to Armen.

Product potential
At the moment it’s hard to gauge how well Oncophage will do there commercially. Russia’s economic boom means that paying for the medicine is less of an issue than in the past, and the vaccine addresses a population around four-fold bigger than that for other approved kidney cancer drugs. The size of the Russian cancer treatment market leaped from around $200 million in 2005 to more than $1 billion in 2007.

But the fact remains that Oncophage is aimed at a patient population that would normally be treated with surgery and ‘watchful waiting’, rather than drugs, and that does require that doctors change their thinking, according to Armen.

“The exciting thing about Oncophage is that has the long-term potential to treat all cancers and so could save health systems hundreds of billions of dollars worldwide and realise revenues in the order of tens of billions of dollars,” said Armen.

Russia is a great starting point, he said. “The rate of change in Russia is absolutely remarkable,” said Armen. “But we expect take-up of the product in the first six months to be slow, as we still need to secure reimbursement approval.”

“Private-pay will be driving the first six months, and that may include some medical tourism. After that the public-pay market should kick in and we will see an acceleration in revenues.”

The Russian kidney cancer population is around 20,000 patients a year, of whom at least 50% are eligible for Oncophage. “That’s a respectable number,” said Armen.

US, EU plans
Patients in the USA are likely to have to wait some time for access to the drug however, said Armen, given that an additional, supportive study in intermediate-risk patients will require several years to carry out.

“The US is driven by statistical dogma, and less so by scientific and clinical criteria,” he said, noting that is a relic from when very little was known about the underlying biology of disease. “It’s not the fault of the FDA at all – this is a system-wide issue and the agency cannot make a change on its own. It clearly has the will to make progress in this area.”

As a small company Antigenics has limited resources, so will not move forward with a US registration study without some initiative taken by the FDA, he said. In Europe the aim will be to file sometime in August, with a standard review time of 12-18 months. Approval there could perhaps prompt some dialogue with the US authorities.

Meanwhile, Antigenics is pursuing a follow-up clinical trials programme in additional indications, including melanoma and glioma, and it could be that one of these becomes the first indication in the USA.