Yesterday's thumbs-down by an FDA advisory panel may squelch not only a Genentech bid to get Avastin approved for treating breast cancer but other cancer drugs may now have a tougher time proving their survival rates justify label extensions, an analyst said.
The Oncologic Drugs Advisory Committee (ODAC) voted 5-4 against endorsing Avastin for use in first-line metastatic breast cancer. The panel had concerns about overall survival rates as well as drug toxicity.
Susan Desmond-Hellmann, MD, MPH, president of Genentech product development, said in a statement that she was disappointed by the vote but, “We believe that Avastin can help meet a significant unmet medical need for women with metastatic breast cancer.” She added that the biotech will work with the FDA “to make Avastin a viable treatment option for these patients.”
Two trials of the drug in breast cancer are still ongoing and may yield data by 2009. However, Jim Reddoch, PhD, an analyst with Friedman Billings Ramsey & Co., said an indication in breast cancer is unlikely, especially in the short term.
“We expect the FDA to turn down the application on or before the February 23 [action] date,” he wrote in an investor note this morning.
A rejection of the Genentech application may take $600 million in sales out of the picture, according to Reddoch, who lowered Avastin sales numbers in breast cancer to 10% of the drug's total revenues—roughly in line with current use. The drug was approved for breast cancer in Europe earlier this year.
Another biotech firm, ImClone, is counting on two trials of its drug Erbitux to support an application for use in first-line colon cancer treatment.
“After yesterday's Avastin panel meeting, we think Erbitux will have a harder time being approved in earlier-stage colon cancer,” Reddoch wrote in a second note. That's because the ODAC panel set the bar high for interpreting data in post-marketing studies designed to prove an endpoint known as progression-free survival (PFS).
With Avastin, median PFS was 11.3 months, and 5.8 months without the drug. Either the five dissenters were not convinced PFS is a valid endpoint, or they felt its benefit did not outweigh the risk profile in light of Avastin's added toxicity.
CRYSTAL, a study that ImClone is relying on in colon cancer, has shown a 0.9-month (11%) PFS benefit over the control arm. According to Reddoch, while Erbitux does not show Avastin's toxicity, “it will be difficult to convince this FDA to accept that data as being robust and having sufficient magnitude to justify a first-line approval in colon cancer.”
A second Erbitux trial missed its survival endpoint entirely.
The likelihood that neither trial will enable Imclone to gain the new indication prompted Reddoch to lower Erbitux's 2011 sales estimate by $90 million.