Phase III Study: ASA404 Vascular Disrupting Agent

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LONDON - Antisoma plc said its partner Novartis AG will take ASA404, a vascular disrupting agent, into a second pivotal Phase III trial in the second-line treatment of non-small-cell lung cancer, a move that will open up a bigger market if the trial is positive.

A Phase III trial of the drug as a first-line adjunctive treatment is ongoing. Glyn Edwards, Antisoma's CEO, told an analysts' meeting that moving into second-line treatment, "significantly increases the market potential of this drug. The second line setting is a huge market."

ASA404 is a small molecule that disrupts existing blood vessels in tumors. As such, it has a distinctive mode of action from marketed treatments like Avastin that work by preventing the formation of tumor vasculature by blocking vascular endothelial growth factor, VEGF.

Intriguingly, moving into the second-line trial means ASA404 is likely to be tested on relapsed patients who have been treated with Avastin. While there is no evidence as yet to show ASA404 will work in patients previously exposed to Avastin, the different mechanisms of action suggest this is likely.

"The preclinical data suggest a synergy with Avastin and there is no evidence of overlapping toxicities," Edwards said.

That is important because it opens up the possibility of using combinations of drugs that impact tumor blood vessels, allowing treatment to be optimized for efficacy and side effects. VEGF inhibition blocks the formation of blood vessels throughout the body, leading to potentially life-threatening side effects, including perforation of the gastrointestinal tract. ASA404, on the other hand, acts solely on tumor blood vessels.

The first-line study, Attract-1 is evaluating ASA404 with carboplatin and paclitaxel chemotherapy. In the second-line Attract-2 trial, ASA404 will be administered with docetaxel. "There are positive reasons why we are looking at ASA404 in combination with docetaxel," Edwards said. "In the preclinical data, in different tumor models, you see more than additive effects."

The primary endpoint of the 900 patient Attract-2 study will be overall survival. Recruitment will start before the end of this year. If positive, Edwards said, the data should support a marketing application in 2011. There will be an interim analysis before the end of 2009.

"I'm hugely excited by this opportunity," Edwards added. "It really reinforces the potential of [ASA404] in this indication and reinforces Novartis' commitment to the drug."

ASA404 was discovered by scientists at the Auckland Cancer Society Research Center at Auckland University, New Zealand, and came into London-based Antisoma's portfolio via Cancer Research Technology Ltd, the commercialization arm of the charity Cancer Research UK. It was licensed to Novartis in April 2007 in a deal with a headline value of $890 million.

There have been two Phase II studies of the drug in non-small-cell lung cancer in combination with standard chemotherapy. The first study demonstrated an increased overall survival of five months, from 8.8 months to 14 months, compared with chemotherapy alone.

The second study was a single-arm evaluation trial with a higher dose of ASA404 in combination with the same chemotherapy agents, in which there was a median overall survival of 14.9 months.

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(AHC, Media U.C., By Nuala Moran, July 23, 2008)

Disclaimer:

The information contained in these articles may or may not be in agreement with my own opinions. They are not posted as medical advice of any kind.