West Coast Editor
With off-label use of Herceptin already slowly growing for early stage breast cancer patients, Genentech Inc. said two Phase III trials in that population were stopped after an interim analysis showed the drug offered benefit.
Genentech's stock (NYSE:DNA) closed Tuesday at $72.55, up $3.12, after trading as high as $75.50
Calling the company a "very conservative organization," analyst Eric Schmidt, with SG Cowen & Co. in New York, said the data "have got to be extremely clean" in order for Genentech to stop the trial.
Full data from the Herceptin studies, presented by the National Cancer Institute, won't be seen until the American Society of Clinical Oncology meeting next month, but an NCI press release noted that patients given Herceptin with chemotherapy showed a 52 percent decrease in disease recurrence compared to patients treated with chemotherapy alone.
"The hurdle to stopping [the trials] was very high," Schmidt said, and predicted "exceptional" detailed results at the ASCO meeting.
Colleen Wilson, spokeswoman for South San Francisco-based Genentech, noted the trials were powered to show a 25 percent drop in disease recurrence. Herceptin did more than twice that.
Herceptin's happy news follows by a week the disclosure of positive breast cancer data with the company's Avastin (bevacizumab), approved for colorectal cancer, and follows by more than a month positive results with Avastin against lung cancer - and let Genentech, with 14 marketed products and diverse pipeline, push past Thousand Oaks, Calif.-based Amgen Inc., in terms of market value Tuesday. (See BioWorld Today, March 16, 2005, and April 18, 2005.)
The studies compared Herceptin (trastuzumab), approved in September 1998 for metastatic breast cancer, when given with chemotherapy, to chemotherapy alone as adjuvant therapy after surgery for women with early stage, human epidermal growth factor receptor 2 (HER2)-positive breast cancer.
A network of researchers led by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the North Central Cancer Treatment Group (NCCTG) conducted the trials, as well as the prospectively designed joint interim analysis, after consulting with the FDA.
The NCCTG study enrolled its first patient in June 2000 and has signed up 3,406 patients so far, while the NSABP study began enrollment in March 2000 and lists 2,085 patients. Data from 3,300 patients were used in the interim analysis, and the studies will stop enrolling new patients as existing ones are watched for longer-term data.
Specifically, the studies evaluated the combination of anthracycline and cyclophosphamide followed by paclitaxel, with or without Herceptin, using different treatment schedules of paclitaxel in women with HER2-positive breast cancer. Adverse events in those studies proved consistent with those seen in previous Herceptin trials.
Each of the studies has an independent, external data monitoring committee that reviewed results, including those related to cardiac safety, and found 3 percent to 4 percent more cases of serious or life-threatening cardiac events, most commonly congestive heart failure, in patients who got Herceptin combined with chemo.
Under its current label, Herceptin is indicated for weekly treatment of patients both as first-line therapy in combination with paclitaxel and as a single agent in second-line and third-line settings. The drug is marketed in the U.S. by Genentech, in Japan by Tokyo-based Chugai Pharmaceutical Co. Ltd., and internationally by Genentech's 58 percent owner F. Hoffmann-La Roche Ltd., of Basel, Switzerland.
Researchers have said using targeted therapies such as Herceptin early rather than late could get better results, Wilson acknowledged.
"Obviously in cancer it's important to prove efficacy in the metastatic stage so you know you're giving patients the best chance in comparing standards of care," she told BioWorld Today, but earlier treatment "seems to be more efficacious, given the biology of the disease."
Christopher Raymond, analyst with Robert Baird & Co. in Chicago, said figures from CancerConsultants Inc. indicate "Herceptin has indeed already begun to see gradual off-label use in earlier-stage breast cancer patients," and he expects that use to grow at a faster rate now.
Schmidt, however, was skeptical.
"That's the hope, but it's not necessarily clear that just because a therapy is targeted, it will work earlier," he said. In the case of Avastin, some of Cowen's sources said the drug might not show much efficacy in the adjuvant setting against colorectal cancer. Cowen is planning a conference call Friday that might shed more light on the matter, Schmidt said.
Based on the positive results from four recent Phase III trial analyses in the past five weeks - three of which took place earlier than expected - Genentech said it will "continue to evaluate its expected short- and long-term product demand" and gauge manufacturing plans accordingly, with more on that to come when the company reports its second-quarter earnings.
"We don't have any specifics yet," Wilson said.
Meanwhile, Genentech's market value beat that of Amgen, which had its stock (NASDAQ:AMGN) close at $57.20 Tuesday, down 83 cents, with a total market value of $72.07 billion (1.26 billion shares outstanding) compared to Genentech's $75.91 billion (about 1.04 billion shares outstanding).
"They're very close, and it's something I don't think should be the case right now," Schmidt told BioWorld Today. "The market is valuing one of these companies too low and the other too high."
Genentech has "three or four years of execution" before the company achieves "anything like" the revenue stream of the mighty Amgen, he said.
"It's remarkable, but Genentech is more richly valued than Merck, Abbott, AstraZeneca, Eli Lilly," Schmidt said.