Genentech Research Articles

Combined Analysis of Efficacy: The Addition of Bevacizumab to Fluorouracil/Leucovorin Improves Survival for Patients With Metastatic Colorectal Cancer

Bevacizumab (Avastin; Genentech Inc, South San Francisco, CA), a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody that inhibits tumor angiogenesis, has demonstrated survival benefit in patients with previously untreated metastatic colorectal cancer when combined with irinotecan/fluorouracil (FU)/leucovorin (LV; IFL). Three randomized clinical studies have evaluated bevacizumab in combination with FU/LV alone. A combined analysis of raw data from these studies was performed to better assess the efficacy of bevacizumab with FU/LV. The analysis used primary efficacy data from three independent studies, including 241 patients in a combined control group receiving either FU/LV or IFL and 249 patients receiving FU/LV/bevacizumab (5 mg/kg once every 2 weeks). The efficacy data included response rate, progression-free survival, and overall survival. The median duration of survival was 17.9 months in the FU/LV/bevacizumab group, compared with 14.6 months in the combined control group, corresponding to a hazard ratio for death of 0.74 (P = .008). The median duration of progression-free survival was 8.8 months in the FU/LV/bevacizumab group, compared with 5.6 months in the combined control group, corresponding to a hazard ratio for disease progression of 0.63 (P < or = .0001). The addition of bevacizumab also improved the response rate (34.1% v 24.5%; P = .019). The addition of bevacizumab to FU/LV provides a statistically significant and clinically relevant benefit to patients with previously untreated metastatic colorectal cancer.

Royalty Award Against Genentech Overturned

Royalty Award Against Genentech Overturned

Agensys and Genentech in Cancer Antibody Agreement

Agensys and Genentech in Cancer Antibody Agreement

Clinical pharmacokinetics of bevacizumab following every 2- or every 3-week dosing

3041 Background: Bevacizumab (BV) is an IgG1 monoclonal antibody that inhibits all isoforms of VEGF-A. The addition of BV to irinotecan/5-FU/LV (bIFL) in patients with metastatic colorectal carcinoma resulted in a 34% reduction in the risk of death, as compared to bIFL alone (p=0.00004), and in a median survival increase from 15.6 to 20.3 months (Hurwitz, ASCO 2003). Due to its long elimination half-life, BV was administered every 2 or 3 weeks in Phase II and III clinical trials. This analysis further characterizes the impact of dosing schedules on BV exposure. Methods: A retrospective non-compartmental analysis was conducted to compare several measures of drug exposure, using observed data from 2 Phase II dose-ranging trials (1 study in colorectal carcinoma (AVF0780g) and 1 in non small cell carcinoma (AVF0757g)), where BV was administered at doses of 5 and 7.5 mg/kg every 2 or 3 weeks, respectively. Simulations (500 subjects) were also performed to compare drug exposure for different administration frequencies, using a 2-compartment population PK model that was recently developed based on data from 491 subjects from 8 clinical trials. Results: Observed and simulated steady-state concentrations following BV dosing at 2.5 mg/kg/week every 2 or 3 weeks, are presented in the table below: Conclusions: Administration of BV at 2.5 mg/kg/week every 2 or 3 weeks results in similar overall exposure, due to its slow clearance and long elimination half-life of 20 days. Thus, the frequency of BV administration can easily be coordinated with the schedule of administration of the cytotoxic agents. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Inc. Genentech, Inc. Genentech, Inc. Genentech, Inc. Genentech Inc.

Chiron claims against Genentech patent dismissed again

Chiron claims against Genentech patent dismissed again

Bootstrap resampling methods: something for nothing?

Bootstrap resampling methods: something for nothing?

Bevacizumab [Avastin; Genentech] has been launched in the US.

Bevacizumab [Avastin; Genentech] has been launched in the US.

Blood Pressure and the Survival of Renal Allografts from Living Donors

Levels of BP have been associated with increasing rates of renal allograft failure from cadaveric donors, independent of renal function. The effect of BP, a modifiable risk factor, on the failure rates of renal allografts from living donors is unknown and maybe obscured by the rate of decline of renal function from this source of organs. A nonconcurrent cohort study collecting data from 392 recipients of a renal allograft from a living donor during 1990 to 2001 was performed. Multivariable Cox regression models were fit by means of time-varying terms for systolic BP (SBP), diastolic BP (DBP), mean arterial BP (MAP), pulse pressure, and renal function during the first year after transplantation to study the association of BP and the time to allograft failure. Potential nonlinear relationships were considered by fractional polynomial terms. Recipient gender, preemptive transplantation, and time-varying terms for the natural logarithm of creatinine clearance and acute rejection were retained in the multivariable model. Including separate multivariable models with nonlinear terms for SBP (P = 0.02), for DBP (P = 0.02), or for MAP (P = 0.05) during the first year significantly improved the fit of the respective models and confirmed that there is an association of BP and allograft failure independent of renal function. Pulse pressure had neither a linear nor nonlinear association with allograft failure. In this nonconcurrent study, the level of BP during the first year affected the survival of renal allografts from living donors, independent of renal function. Further investigation is required to confirm the level of BP that is optimal to prevent foreshortened duration of survival.

History of antibody therapy for non-Hodgkin’s lymphoma

Monoclonal antibodies (mAbs) were the first successful targeted therapy for cancer. In contrast to the nonspecific nature of most chemotherapy, antibodies bind with high specificity to cell-surface antigens, resulting in targeted killing of malignant cells, relative sparing of normal tissues, and low toxicity. Antibody therapy has undergone substantial development since Ehrlich’s notion of a “magic bullet,” in 1890. It was not until the 1970s, however, that mAbs became viable as therapeutic tools and clinical studies showed them to be effective. The results were most impressive in hematologic malignancies, especially B-cell non-Hodgkin’s lymphoma. In 1997, rituximab (Rituxan; Genentech Inc, South San Francisco, CA, and Biogen Idec Inc, Cambridge, MA) became the first mAb approved by the US Food and Drug Administration for use in the treatment of cancer. The first approval for a radiolabeled antibody to treat cancer was in 2002 for 90Y ibritumomab tiuxetan (Zevalin; Biogen Idec). This is a conjugate of an anti-CD20 mAb (ibritumomab, the murine parent of rituximab) with the beta-emitter radionuclide 90Y. 90Y ibritumomab tiuxetan has been shown to be safe and effective in the indicated patient population. Other radioimmunoconjugates are being investigated for the treatment of non-Hodgkin’s lymphoma, as are several immunotoxins. This article reviews important events in the development of mAb therapy and radioimmunotherapy for B-cell non-Hodgkin’s lymphoma.

Pharmacokinetics and pharmacodynamics: Maximizing the clinical potential of Erlotinib (Tarceva)

Pharmacokinetic and pharmacodynamic studies have an important role in the optimization of targeted agents. Phase I pharmacokinetic studies show that treatment with erlotinib HCl (Tarceva; Genentech Inc, South San Francisco, CA), an orally available epidermal growth factor receptor (HER1/EGFR)-tyrosine kinase inhibitor, on a daily, uninterrupted schedule is feasible. Also, plasma drug concentrations, likely to be clinically effective based on preclinical studies, are consistently achieved at the recommended phase II dose of 150 mg/day, the maximum tolerated dose. Pharmacodynamic studies are in progress to assess the activation of HER1/EGFR and associated downstream signaling pathways in tissue samples from patients treated with erlotinib. Expression of p27 is identified as a potential surrogate marker of erlotinib activity, and is a focus of ongoing and future studies. Also, studies indicate that skin may be a useful surrogate tissue for evaluating the pharmacodynamic effects of therapy. These studies will hopefully enable us to accurately assess the extent of target inhibition in patients treated with erlotinib and help optimize its clinical use.

Pharmacokinetics and pharmacodynamics: Maximizing the clinical potential of Erlotinib (Tarceva)

Pharmacokinetic and pharmacodynamic studies have an important role in the optimization of targeted agents. Phase I pharmacokinetic studies show that treatment with erlotinib HCl (Tarceva; Genentech Inc, South San Francisco, CA), an orally available epidermal growth factor receptor (HER1/EGFR)-tyrosine kinase inhibitor, on a daily, uninterrupted schedule is feasible. Also, plasma drug concentrations, likely to be clinically effective based on preclinical studies, are consistently achieved at the recommended phase II dose of 150 mg/day, the maximum tolerated dose. Pharmacodynamic studies are in progress to assess the activation of HER1/EGFR and associated downstream signaling pathways in tissue samples from patients treated with erlotinib. Expression of p27 is identified as a potential surrogate marker of erlotinib activity, and is a focus of ongoing and future studies. Also, studies indicate that skin may be a useful surrogate tissue for evaluating the pharmacodynamic effects of therapy. These studies will hopefully enable us to accurately assess the extent of target inhibition in patients treated with erlotinib and help optimize its clinical use.

Boom in sales expected in 2003 by Bayer, Genentech

Boom in sales expected in 2003 by Bayer, Genentech

Genentech, Inc., v. Amgen, Inc. (No.01-1098)

Biotechnology Law ReportVol. 21, No. 4 TextsGenentech, Inc., v. Amgen, Inc. (No.01-1098)Published Online:5 Jul 2004https://doi.org/10.1089/073003102760255414AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byMarket Intermediation, Publicness, and Securities Class ActionsSSRN Electronic JournalGene Patents Under Fire: Weighing the Costs and BenefitsSSRN Electronic Journal Volume 21Issue 4Aug 2002 To cite this article:Genentech, Inc., v. Amgen, Inc. (No.01-1098).Biotechnology Law Report.Aug 2002.394-403.http://doi.org/10.1089/073003102760255414Published in Volume: 21 Issue 4: July 5, 2004PDF download

VaxGen Amends Agreement with Genentech for AIDSVAX

VaxGen Amends Agreement with Genentech for AIDSVAX

Jury rules Genentech must pay $300 million in royalty dispute

Jury rules Genentech must pay $300 million in royalty dispute

Xenova out-licenses preclinical technology to Genentech

Xenova out-licenses preclinical technology to Genentech

Bio-Technology General Corp. and Bio-Technology General (Israel) Ltd. v. Genentech, Inc.

Bio-Technology General Corp. and Bio-Technology General (Israel) Ltd. v. Genentech, Inc.

Decision of 12 October 2000, Genentech, Inc., T 0400/99

Decision of 12 October 2000, Genentech, Inc., T 0400/99

Roche to get richer on Genentech shares

Roche to get richer on Genentech shares

Genentech's 2nd IPO

Genentech's 2nd IPO