Avastin has now racked up three positive studies in ovarian cancer, the next tumour type Roche (OTCQX:RHHBY) is hoping to win approval to treat. Unfortunately, the beleaguered antibody is struggling to find friends at the moment, and confidence that the antibody will become a commercial success in this setting, possibly even win approval, has taken a knock.
There is certainly a need for new therapies in ovarian cancer and for the second year running Avastin data in this setting is likely to attract much attention at oncology conferences (Asco - Avastin in ovarian cancer prompts wait and see response, June 7, 2010). Crucially, evidence that the drug helps women live longer overall is awaited, while heightened concerns about the drug’s side effects means safety data will be scrutinised. For confidence to return, Avastin needs to shine on both measures.
This measure, of progression free survival, was the primary endpoint of the study and was met successfully; so far Roche has not revealed any figures on how long each group lived before progression, or any other details.
The Oceans study was conducted in women who had already received chemotherapy and relapsed, so is slightly different from the other studies that have yielded data in ovarian cancer, GOG 0218 and ICON7. These tested newly diagnosed women and both also delayed disease progression. The former, run by the US National Institutes of Health, detected a four-month improvement in disease progression over placebo whilst the latter generated a two-month improvement.
At the Asco cancer conference last year doctors agreed these results were very interesting, but evidence of an overall survival benefit was a key interest. All of these trials are measuring this as a secondary outcome but it has not yet become available – a result that remains an important measure for the drug in this setting.
Side effect focus
However, an article in the Journal of American Medical Association (JAMA) last week, following the withdrawal of US approval in breast cancer, means the side effect profile of Avastin is becoming increasingly a point of interest.
Although lack of evidence of efficacy largely prompted the FDA to take action last year, the regulator made it clear that Avastin’s adverse event profile significantly contributed to the decision (Roche fighting Avastin's corner as support officially withdrawn in breast cancer, December 17, 2010).
The recent JAMA article brings this issue to the foreground once more. The journal published a meta-analysis that looked at data from just over 10,000 patients who were treated with Avastin over 16 studies conducted in several tumour types, some of which the drug is approved to treat but some of which remain experimental. They concluded that Avastin plus chemotherapy increased the rate of fatal adverse events by approximately 50% over control arms, with certain tumour settings and dosages particularly susceptible. In particular a chemotherapy backbone containing a taxane or platinum-based therapy seemed to be associated with these events.
This finding is particularly relevant for ovarian cancer, which is primarily treated with platinum-based chemotherapy agents. Treatment strategies are led by the description of relapse as platinum sensitive or platinum resistant – concern that these regimens exacerbate the side effect profile of Avastin, possibly even leading to more deaths, will be damaging for both the drug’s regulatory and commercial prospects.
Roche acknowledged the challenges facing Avastin last week, downgrading its peak sales forecast for the drug from Sfr8-9bn to Sfr7bn ($7.3bn). Prior to this, consensus among financial analysts stood around SFr8bn, according to EvaluatePharma, a figure likely to edge lower.
However most of the analysts’ forecasts that comprise that consensus include some contribution from ovarian cancer – Roche’s guidance does not. Analysts believe ovarian represents anything from a Sfr400m to Sfr1bn opportunity, although all acknowledge this still a big unknown.
More in-depth data is needed to paint a clearer picture of what could be a major growth driver for Avastin, or another disappointment.