Antisoma and Novartis lung cancer drug ASA404 flops in phase III

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This morning I did a double take at an email alert that flashed through my email:

"ATTRACT-1 phase III trial of ASA404 halted following interim analysis"

Ugh, that's not good news considering the phase II data previously discussed in January looked very promising with a solid improvement (source data), ie median time to tumor progression was 5.5 months by investigator assessment and median survival was 14.9 months when used in combination with carboplatin-paclitaxel compared to the standard alone.

The Antisoma press release was very downbeat and clearly they were not expecting to receive any more funding from their partner, Novartis:

"The planned interim analysis of data from the ATTRACT-1 phase III trial of ASA404 in previously untreated non-small cell lung cancer (NSCLC) has shown that continuation of the trial would be futile, as there is little or no prospect of demonstrating a survival benefit with ASA404 in this setting. The ATTRACT-1 trial will therefore be halted."

Novartis (a client, but not on this particular agent) bought the global rights to ASA404 (vadimezan) from Antisoma, a British company, approximately three years ago. ASA404 was leading a new class of chemotherapy agents known as vascular targeting or disrupting agents, designed to inhibit angiogenesis and disrupt the flow of blood to tumours. The concept works in a different way to Roche and Genentech's bevacizumab (Avastin), which starves tumours from growing new blood vessels and proliferating the cancer mass.  ASA404 exerts direct and indirect effects on endothelial cells rather than the VEGF receptor, as this diagram shows:

Antisoma and Novartis lung cancer drug ASA404 flops in phase III
Source: Novartis Oncology

Novartis and Antisoma were also developing ASA404 in breast cancer as well as non-small cell lung cancer, so we'll have to wait and see what happens to that program going forward.  For now, the negative news in lung cancer meant that investors cleared out their shares, sending the stock into a major freefall this morning.

It's been a tough year for cancer drugs in lung cancer in 2010 already, following several spectacular rounds of futile data from Pfizer's figitimumab, Novelos's NOV-002 and now ASA404, all of which had promising but early data in phase II, only to stumble in phase III.

  • http://profile.typepad.com/drwestgrace DrWestGRACE

    I think one other important take home message is that it’s a mistake to presume that a 14-18 month median survival on a phase II trial means that an agent will deliver in a phase III trial. I definitely think the agents you mentioned above deserve to be tested properly in a prospective phase III trial, but we tend to see people take the press releases from phase II work as if the phase III trial is a formality, as if the vast majority of phase II trials don’t fail to deliver in phase III trials.
    I wish it weren’t a rare occasion to have a positive phase III trial in lung cancer, and I hate to be a “wet blanket” when I urge caution in projecting that a company’s glowing praise for its compound will translate to a commercially available product, but it turns out that it’s most appropriate to see significant benefits as the exception and not the rule.

  • http://profile.typepad.com/maverickny MaverickNY

    You’re totally right that that many extrapolate to phase III trials and assume that whatever happens in phase II will be repeated. Sadly, there have been many cautionary tales over the last 12 months in oncology to remind us that the ones that do make it to market are fewer rather than most.
    That said, given the number of failures in lung cancer recently, many of us are left wondering what lessons can be learned from them for the future?

  • Starlight

    Oxigene inc. has the solution for Novartis.
    Cheap company…