Roche Avastin Trials Not as Good as Early Tests (Update2)
It's going to be interesting to see how the FDA handles this because they approved Bev in Breast after the advisory panel voted no.
By Molly Peterson and Dermot Doherty
July 16 (Bloomberg) -- Roche Holding AG’s top-seller Avastin didn’t slow breast tumors in new studies as much as in earlier tests used to win approval, according to U.S. regulators weighing whether to permit sales to continue for this purpose.
Avastin paired with chemotherapy didn’t help patients survive longer than use of the other drugs alone, and those receiving the Roche medicine had more serious side effects, according to a Food and Drug Administration staff review today. FDA advisers will meet July 20 to evaluate Avastin and consider whether use in breast cancer should be continued, expanded, or halted. The shares fell the most in more than a year.
Roche, Europe’s largest drugmaker, won FDA approval of Avastin for breast cancer in 2008 under an accelerated review that required the company to complete trials proving the treatment, with $5.97 billion in sales last year, extends survival or enhances quality of life. Withdrawal of approval may trim as much as $1 billion from annual sales by 2015, said Jack Scannell, an analyst with Sanford C. Bernstein & Co. in London.
“My gut feeling would be that it doesn’t look good for Avastin,” said Nick Turner, an analyst at Mirabaud Securities in London, in a telephone interview today. “The real worry here may be that the adverse events associated with Avastin are overriding any anti-cancer effect.”
Roche, based in Basel, Switzerland, fell 6.3 Swiss francs, or 4.2 percent, to 144.5 francs at the 5:30 p.m. close in Zurich, the most since April 22, 2009. The stock has lost 18 percent this year.
Blood-Vessel Growth
Avastin is the first medicine to fight cancer by blocking the growth of blood vessels that feed tumors, a process called angiogenesis. It targets a chemical signal known as vascular endothelial growth factor, or VEGF. Avastin was developed by Roche’s San Francisco-based Genentech unit, fully acquired by the European drugmaker last year for $46.8 billion.
Breast cancer is the most common malignancy in females and strikes about 1 million women a year globally, according to the Geneva-based World Health Organization. Avastin is approved for about three quarters of women whose breast cancer has been recently diagnosed as having spread to other organs. It doesn’t include women who have a mutation to the HER2 protein, a known risk factor. Patients with HER2 mutations are eligible for another Roche drug, Herceptin.
The FDA clearance of Avastin for breast cancer overruled an advisory panel that concluded the benefit of slowing the spread of tumors wasn’t worth the risk of side effects including high blood pressure and death. The drug, also approved for brain, lung and colon tumors, costs about $50,000 a year.
Early Trial
Approval was based on a clinical trial, called E2100, which showed Avastin slowed the spread of breast cancer by an additional 5.5 months when paired with paclitaxel chemotherapy, compared with the other drug alone, the FDA said today.
One trial completed since then, called Avado, showed that a high dose of Avastin paired with docetaxel chemotherapy extended the time patients lived without their disease worsening by 0.9 months, compared with treatment with chemotherapy alone, the FDA report said. A lower dose of Avastin gave patients 0.8 months.
A second trial finished after approval, called Ribbon-1, found that Avastin combined with taxane or anthracycline-based chemotherapies stalled tumor growth by 1.2 months, compared to treatment with chemotherapy alone, the report said. Patients who got Avastin combined with Xeloda lived 2.9 months longer without their disease progressing, compared to chemotherapy alone.
‘Consistent’ Benefit
“What we have learned through these trials is that there is a consistent magnitude of benefit,” said Philippe Bishop, Roche’s vice president of clinical development for Avastin, in a telephone interview yesterday. “There was no significant increase in overall survival, but what is important in our understanding is that there was also no added detriment.”
Drugs that win conditional clearance through the FDA’s accelerated-approval program can later be pulled from the market if subsequent data fails to show that a treatment increases long-term survival or slows progression of the disease while improving quality of life.
Avastin was effective in keeping the disease at bay, though studies have been unable to show a quality-of-life improvement, Citigroup analyst Mark Dainty said in a July 8 research note.
“The key question is whether FDA will accept this progression-free survival benefit as a clinical benefit in absence of an improvement in measured quality of life and without a proven extension of survival,” Dainty said.
Mylotarg Withdrawn
Pfizer Inc.’s leukemia treatment Mylotarg last month became the first drug with accelerated approval to come off the market after studies linked it to deaths from liver and lung complications and failed to prove it works. New York-based Pfizer, the world’s largest drugmaker, voluntarily halted sales of the drug, which won accelerated FDA approval 10 years ago based on preliminary data showing improved remission rates.
“We are cautiously optimistic on the outcome for Roche,” Scannell, the Bernstein analyst, said in his research report yesterday. “The drug works less well than people would have hoped several years ago and it is very expensive. Nonetheless, the overwhelming majority of breast cancer specialists think it has a use in certain patients.”
To contact the reporters on this story: Molly Peterson in Washington at mpeterson9@bloomberg.net: Dermot Doherty in Geneva at ddoherty9@bloomberg.net
Last Updated: July 16, 2010 12:19 EDT
