Genentech Continues Its Spectacular Spring Romp
Pharma’s Cutting Edge
Vol. 3 Number 5 - May 2005
Genentech Continues Its Spectacular Spring Romp in May
Investors are celebrating Genentech’s vernus mirabilis, when nearly everything they touch turns to gold. Recently, I haven’t bothered ruminating much on individual companies’ successes and failures, because so much of that depends on intangible, stage-dependent risk factors…what otherwise might be called luck.
But I have to believe that Genentech’s recent run is a bit different. Sure, luck is playing a role, but I believe there are real lessons for investors and other drug developers to learn from Genentech’s ongoing example.
Genentech’s most recent apparent triumph came last week when they announced preliminary, interim results from the 716-subject MARINA trial, in which Lucentis (ranibizumab), an anti-VEGF-A humanized monoclonal antibody fragment, was compared with placebo in the treatment of minimally classic or occult wet age-related macular degeneration (AMD). Approximately 95 percent of Lucentis-treated subjects maintained or improved vision compare to approximately 62 percent of those treated with sham injection. Patients treated with Lucentis for 12 months had, on average, a significant improvement in visual acuity compared to their visual acuity at study entry.
If substantiated, Lucentis would be the first therapy to improve vision in AMD patients; other therapies merely halt progression. Of course, some ‘analysts’ took the press release for a full data release and were already proclaiming Lucentis the clear winner in the wet AMD wars, in which Genentech will battle Eyetech (Macugen) and Alcon (Retaane) for market domination in the near future. One easily swayed analyst, who shall remain nameless, already forecasted Genentech stealing 80% of Eyetech’s market share! Ummm…I don’t think so. Nevertheless, Lucentis seems to work at least as well as Genentech had intended.
“These Lucentis data exceeded our expectations. We are excited that our pioneering work at Genentech in the field of angiogenesis has again translated into a potential new treatment option for patients with such a significant unmet medical need,” said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer. Of course, Barron was referring to Genentech’s pioneer Avastin (bevacizumab), a humanized monoclonal anti-VEGF antibody, which is currently indicated as first-line treatment, in combination with 5-FU, for metastatic colon cancer but which is destined to become a first-line treatment for non-small cell lung cancer and recurrent or metastatic breast cancer, an adjuvant treatment for colon cancer, and which is being tested in Phase 3 trials in advanced renal cell carcinoma, locally advanced or metastatic pancreatic carcinoma, and metastatic hormone-refractory prostate carcinoma.
“The fact that Avastin has now demonstrated significant clinical benefits in three of the most common types of cancer [colon, breast and lung] highlights how this antiangiogenesis drug has the potential to completely change the way we treat cancer, as it could become the mainstay of treatment for a whole range of cancers,” said Kathy Miller, lead investigator of Avastin Study E2100 in locally recurrent or metastatic breast cancer.
To think that less than three years ago, Avastin was nearly written off by skeptics as a failure in breast cancer, and, if Wall Street had its way, would have been abandoned by Genentech.
Despite the excitement surrounding Avastin, Genenetch’s real triumph at this year’s ASCO meeting concerned their seven-year-old breast-cancer stalwart, Herceptin (trastuzumab), a monoclonal antibody that inhibits activity of the HER2 proto-oncogene and is currently indicated as monotherapy for treatment of patients with metastatic breast cancer whose tumors over-express HER2 and who have received one or more chemotherapy regimens for their metastatic disease. Herceptin in combination with paclitaxel is indicated for treatment of patients with metastatic breast cancer whose tumors over-express HER2 and who have not received chemotherapy for their metastatic disease. Over-expression of HER2 occurs in about 25% of breast cancers.
The latest tests of Herceptin, revealed at ASCO, indicate that Herceptin is effective as adjuvant treatment in combination with chemotherapy for early breast cancer, cutting the risk of recurrence in half and extending overall survival by an unspecified period. breast cancer, already at the interim analysis, is a major breakthrough in the treatment of this aggressive disease. These results now add to the growing body of evidence that Herceptin should be considered the foundation of care for HER2-positive breast cancer patients, regardless of the stage of their disease.
Jose Baselga, Barcelona: “The applause after the presentation seemed like an opera kind of thing. We were gone from the stage and people kept applauding. I’ve never seen anything like it, ever, and I’ve been at ASCO for 20 years.”
Steven Harr, Morgan Stanley: “The excitement from the audience after the presentation of the Herceptin data was palpable…Net-net, it was an amazing day and monumental week for the company. The data lived up to even the most optimistic expectations.”
At least two factors besides luck and scientific strength can explain Genentech’s continued success—vision and the willingness to take measured risks to fulfill it. That Genentech’s leaders The news was another example of persistence paying off for Herceptin, which initially was also deemed a failure. It wasn’t until Genentech later showed that it worked well in patients whose tumors overexpressed HER2 that the drug was approved. These new data mean that roughly 200,000 women with breast cancer will now likely be tested to see if Herceptin could help them. The tests are made by Abbott Laboratories.
The academic medical community and Wall Street analyst responses to the Herceptin results were overwhelmingly positive.
Norman Wolmark, Pittsburgh: “The differences that we’re seeing there are among the greatest that I have seen for years and years and years.”
Martine Piccart, Brussels “In the advanced breast cancer setting, Herceptin has already demonstrated that it prolongs patients’ lives. To see such impressive results with Herceptin in early-stage have vision is patently obvious. That they have the will to pursue it is revealed in the depth and breadth of the clinical programs supporting their biggest drugs. In oncology, they routinely design trials to demonstrate survival advantages, the most difficult hurdle a drug can clear. ”
[Conducting survival studies] goes to our core values. We want to make drugs that make a big difference. We are asking patients to pay a lot for these drugs. We don’t want them to pay for an incremental benefit,” said Genentech CEO Arthur Levinson in a recent Business Week interview.
Genentech is clearly the torch-bearer in targeted oncology therapeutics. If they choose to place similar resources on another therapeutic area—immune-mediated diseases is likely—we will see how well vision, tenacity, and a penchant for risk-taking translate beyond their comfort zone. I wouldn’t bet against them.
