Sunday, Jun 3, 2007
Chicago -- June 3, 2007 --Genentech, Inc. (NYSE: DNA) today announced results from early studies of several investigational cancer agents targeting the HER (human epidermal growth factor receptor) pathway and pro-apoptotic receptors that induce apoptosis (cell death). These results, including data from studies of pertuzumab, trastuzumab-DM1 (T-DM1), Apomab and recombinant human (Rh) Apo2L/TRAIL, were presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO).
"Until there is a cure for cancer, Genentech will continue to use our understanding of cancer biology to identify new strategies to fight this disease,"said Susan Desmond-Hellmann, M.D., M.P.H., president, Product Development at Genentech. "Building upon the foundation laid by Rituxan, Herceptin, Avastin and Tarceva, we hope that these new investigational molecules may one day become part of the next generation of approved targeted therapies to improve outcomes for patients."
Results from a Phase II Randomized, Placebo-Controlled, Double-Blind Trial Suggest Improved PFS with the Addition of Pertuzumab to Gemcitabine in Patients with Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer (Abstract #5507 —Sunday, June 3, 2007, 2:30 p.m. CDT)
Data from a randomized Phase II study of pertuzumab plus gemcitabine compared to gemcitabine alone in 130 women with platinum-resistant ovarian, fallopian tube or peritoneal cancer were presented today by Sharmila Makhija, M.D., University of Alabama, Birmingham. Pertuzumab, a humanized monoclonal antibody, is designed to bind to the HER2 receptor — a protein found on the surface of epithelial cells — and inhibit the pairing of HER2 as a co-receptor with other HER family members (HER1/EGFR, HER3 and HER4).
Overall progression-free survival (PFS) increased by 52 percent in patients treated with pertuzumab plus gemcitabine (based on a hazard ratio of 0.66, which can also be stated as a 34 percent reduction in the risk of cancer progression or death). Median PFS was 2.9 months in the pertuzumab plus gemcitabine arm (n=65), and 2.6 months in the gemcitabine-alone arm (n=65). Due to the planned exploratory nature and small sample size of this study, these data do not provide definitive conclusions or reach statistical significance with respect to differences between the treatment arms.
In addition, an exploratory biomarker analysis suggested that women whose ovarian tumors had a specific gene expression profile — a high ratio of HER2 to HER3 gene expression — experienced a significant improvement in PFS when treated with pertuzumab plus gemcitabine, compared to gemcitabine alone. In patients with a higher ratio of HER2 to HER3 gene expression, median PFS was 5.4 months in the pertuzumab plus gemcitabine arm, compared to 1.4 months in the gemcitabine-alone arm. The study's hazard ratio in this patient group was 0.32, which can also be stated as a 68 percent reduction in the risk of cancer progression or death.
In this study, there was an increase in Grade 3/4 neutropenia in patients receiving pertuzumab plus gemcitabine (n=22), compared to patients receiving gemcitabine alone (n=14). Two patients in the pertuzumab plus gemcitabine arm had adverse events resulting in death, compared to three patients in the gemcitabine-alone arm. Thirteen patients had cardiac adverse events in the pertuzumab plus gemcitabine arm, compared to 16 patients in the gemcitabine-alone arm. There was one congestive heart failure event reported in the pertuzumab arm.
Objective Response Rate in a Phase II Multicenter Trial of Pertuzumab, a HER2 Dimerization Inhibitor Monoclonal Antibody, in Combination with Trastuzumab in Patients with HER2-Positive Metastatic Breast Cancer which had Progressed during Trastuzumab Therapy (Abstract #1004 —Saturday, June 2, 2007, 5:30 p.m. CDT)
Also presented were encouraging results from an ongoing Roche-sponsored Phase II study of pertuzumab in combination with Herceptin® (trastuzumab) in 42 women with HER2-positive metastatic breast cancer whose disease had progressed following previous treatment with Herceptin and chemotherapy. Results from a similar study (Abstract #1028) investigating pertuzumab in combination with Herceptin in 11 women with HER2-positive metastatic breast cancer were also presented. Genentech and Roche plan to initiate a Phase III clinical trial evaluating pertuzumab in combination with Herceptin for the first-line treatment of HER2-positive metastatic breast cancer.
A Phase I Study of Trastuzumab-DM1, a First-in-Class HER2 Antibody Drug Conjugate, in Patients with HER2-Positive Metastatic Breast Cancer (Abstract #1042 —Saturday, June 2, 2007, 2:00 p.m. CDT)
Data from an ongoing Phase I study evaluating the safety, tolerability and pharmacokinetic profile of T-DM1 were presented by Muralidhar Beeram, M.D., University of Texas Health Science Center, San Antonio. This was the first study to evaluate T-DM1, a first-in-class investigational HER2 antibody drug conjugate (armed antibody), in human clinical trials. T-DM1 links a targeted therapeutic antibody with a potent chemotherapeutic drug. The trastuzumab portion of T-DM1 binds to the HER2 receptor and delivers chemotherapy to HER2-positive breast cancer cells.
Interim results from this study were reported for 18 patients with HER2-positive metastatic breast cancer whose disease had progressed while on a Herceptin-containing regimen. No cardiac toxicity was observed in this trial. Reversible Grade 4 thrombocytopenia was dose-limiting at 4.8 mg/kg; the maximum tolerated dose (MTD) of T-DM1 every three weeks was 3.6 mg/kg. Four ongoing partial responses have been observed in patients receiving doses of T-DM1 at or below the MTD on this every-three-week schedule. Genentech has also announced plans to initiate a Phase II clinical trial of T-DM1 in HER2-positive metastatic breast cancer.
A Phase I Safety and Pharmacokinetic Study of Apomab, a Human DR5 Agonist Antibody, in Patients with Advanced Cancer (Abstract #3582 — Sunday, June 3, 2007, 8:00 a.m. CDT)
Interim data from a Phase I study evaluating the safety, pharmacokinetic profile and early evidence of anti-cancer efficacy of Apomab in 23 patients with advanced or metastatic solid tumors or non-Hodgkin's lymphoma were presented today by D. Ross Camidge, M.D., Ph.D., University of Colorado, Denver. Apomab is a fully human antibody discovered by Genentech that is designed to specifically bind to and activate a receptor called pro-apoptotic receptor DR5, found on the surface of various types of cancer cells, while sparing normal cells. Apoptosis, or "programmed cell death,"is a process that eliminates damaged or unneeded cells in the body. Often, cancer cells have defects preventing them from undergoing apoptosis, and by binding to DR5, Apomab is designed to stimulate this process.
Interim results suggested that Apomab was tolerated at the five dose levels studied in this trial. The most common treatment-related adverse events were headache, fatigue and chills. Fifty-two percent of patients (n=12) experienced stable disease. Three patients with colorectal cancer, granulosa cell ovarian cancer and appendiceal cancer experienced minor responses or durable stable disease (past eight or more cycles of treatment). Study enrollment is continuing, and further safety and efficacy data will be presented in the future. Genentech has also announced the initiation of two Phase II clinical trials of Apomab, one in non-small cell lung cancer and the other in non-Hodgkin's lymphoma.
A Phase Ib Safety and Pharmacokinetic Study of Recombinant Human Apo2L/TRAIL in Combination with Rituximab in Patients with Low-Grade Non-Hodgkin's Lymphoma (Abstract #8078 — Saturday, June 2, 2007, 8:00 a.m. CDT)
Interim results from an ongoing Phase Ib study evaluating the safety and pharmacokinetic profile of RhApo2L/TRAIL in combination with Rituxan® (Rituximab) in eight patients with low-grade non-Hodgkin's lymphoma who relapsed following a treatment regimen including Rituxan were presented by Howard Burris, M.D., Sarah Cannon Cancer Center, Nashville. RhApo2L/TRAIL is a recombinant (engineered) human protein designed to activate two pro-apoptotic receptors, DR4 and DR5, and is being co-developed by Genentech and Amgen.
Based on interim study data, the combination of RhApo2L/TRAIL and Rituxan appeared safe and showed evidence of activity with two patients experiencing a complete response, one a partial response and five patients having stable disease. Serious adverse events included one case of Grade 4 neutropenic sepsis and one case of Grade 3 ileus.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures, and commercializes biotherapeutics for significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from, or are based on, Genentech science. Genentech manufactures and commercializes multiple biotechnology products and licenses several additional products to other companies. The company has headquarters in South San Francisco, Calif., and is listed on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit http://www.gene.com.
For the full prescribing information for Tarceva® and the full prescribing information and Boxed Warnings for Rituxan®, Herceptin®, and Avastin® please visit http://www.gene.com.
This press release contains forward-looking statements regarding the potential of our investigational molecules. Such statements are predictions and involve risks and uncertainties such that actual results may differ materially. Among other things, the potential of our investigational molecules may be affected by a number of factors, including unexpected safety, efficacy or manufacturing issues, additional time requirements for data analysis, BLA preparation and decision making, FDA actions or delays, failure to obtain or maintain FDA approval, competition, pricing, reimbursement, the ability to supply product, product withdrawals, new product approvals and launches, or intellectual property or contract rights. Please also refer to Genentech's periodic reports filed with the Securities and Exchange Commission. Genentech disclaims, and does not undertake any obligation to, update or revise any forward-looking statements in this press release.