Preliminary Pre-Planned Interim Analysis Shows Negative Effect on Progression-Free Survival
THOUSAND OAKS, CA, USA | Mar 22, 2007 | Amgen (NASDAQ: AMGN) today announced that it has discontinued Vectibix(TM) (panitumumab) treatment in the PACCE trial evaluating the addition of Vectibix to standard chemotherapy and Avastin(R)(bevacizumab) for the treatment of first-line metastatic colorectal cancer (mCRC). The PACCE trial investigated a treatment regimen that used dual biologics combined with oxaliplatin- or irinotecan-based chemotherapy. This regimen is not currently used in clinical practice.
The decision to discontinue Vectibix treatment in the trial was based on a preliminary review of data from a pre-planned interim efficacy analysis scheduled after the first 231 events (death or disease progression). This analysis revealed a statistically significant difference in progression-free survival in favor of the control arm. An unplanned analysis of overall survival also demonstrated a statistically significant difference favoring the control arm. Additional analyses are ongoing, and Amgen plans to present the results at an upcoming scientific forum.
"Patient safety is Amgen’s top priority. For this reason, we have decided to discontinue Vectibix treatment in the PACCE trial while we complete additional analyses of these preliminary results. We had hoped that adding Vectibix to the current U.S. standard-of-care for patients newly-diagnosed with mCRC would improve outcomes without excessive added toxicity. Unfortunately, it appears that adding Vectibix to Avastin, when used in combination with oxaliplatin- or irinotecan-based chemotherapy, increased toxicity, without improving efficacy," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen.
Amgen has notified the FDA and study investigators that patients who are still receiving treatment in the PACCE study should discontinue Vectibix treatment. Patients will have the option of continuing per protocol treatment without Vectibix.
In January 2007, Amgen informed all investigators and regulatory authorities about safety information arising from a planned interim safety analysis of the PACCE trial. A review of the interim analysis showed an increased incidence of grade 3 severe events of diarrhea, dehydration and infections in the Vectibix-treated patients. In addition, an increased incidence of pulmonary embolism was observed in patients who received Vectibix compared with those who did not (4 percent and 2 percent, respectively). One (<1 percent) fatal event of pulmonary embolism occurred in a patient receiving Vectibix.
Amgen is continuing to explore Vectibix as a single biologic combined with chemotherapy in Phase 3 first- and second-line registrational trials. No other clinical studies are being modified at this time. However Amgen is evaluating data across all studies.
PACCE Study Design
The PACCE (Panitumumab Advanced Colorectal Cancer Evaluation) study is a Phase 3b randomized, open-label clinical trial evaluating oxaliplatin- and irinotecan-based chemotherapy and Avastin with and without Vectibix in the first-line treatment of patients with metastatic colorectal cancer. The trial is powered to show a 30 percent improvement in progression-free survival, the primary endpoint. Secondary endpoints include response rate, overall survival, duration of response and safety. The PACCE trial enrolled 1,054 patients (824 patients were randomized to receive oxaliplatin-based chemotherapy, and 230 patients were randomized to receive irinotecan-based chemotherapy) at 240 trial sites in the United States between Q1 2005 and Q3 2006.
About Vectibix
Vectibix is indicated for the treatment of patients with epidermal growth factor receptor- (EGFr) expressing metastatic colorectal cancer after disease progression on, or following fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens. The effectiveness of Vectibix for the treatment of EGFr-expressing, metastatic colorectal carcinoma is based on progression-free survival. Currently no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Vectibix.
Important Product Safety Information
Dermatologic toxicities, related to Vectibix blockade of EGF binding and subsequent inhibition of EGF receptor-mediated signaling pathways, included but were not limited to dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Dermatologic toxicities were reported in 89 percent of patients treated with Vectibix and were severe in 12 percent of patients. Severe dermatologic toxicities were complicated by infection, including sepsis, septic death, and abscesses requiring incisions and drainage. Vectibix may need to be withheld or discontinued for severe dermatologic toxicities.
Severe infusion reactions occurred with Vectibix in approximately 1 percent of patients. Severe infusion reactions were identified as anaphylactic reactions, bronchospasm, fever, chills, and hypotension. Although fatal infusion reactions have not been reported with Vectibix, they have occurred with other monoclonal antibody products. Severe infusion reactions require stopping the infusion and possibly permanently discontinuing Vectibix, depending on the severity and/or persistence of the reaction.
About Amgen
Amgen discovers, develops and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science’s promise by bringing safe, effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people’s lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
Forward Looking Statement
This news release contains forward-looking statements that involve significant risks and uncertainties, including those discussed below and others that can be found in Amgen’s Form 10-K for the year ended Dec. 31, 2006, and in Amgen’s periodic reports on Form 10-Q and Form 8-K. Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify side effects or manufacturing problems with our products after they are on the market.
In addition, sales of our products are affected by the availability of reimbursement and the reimbursement policies imposed by third party payors, including governments, private insurance plans and managed care providers, and may be affected by domestic and international trends toward managed care and healthcare cost containment as well as possible U.S. legislation affecting pharmaceutical pricing and reimbursement. Government regulations and reimbursement policies may affect the development, usage and pricing of our products. In addition, we compete with other companies with respect to some of our marketed products as well as for the discovery and development of new products. We believe that some of our newer products, product candidates or new indications for existing products, may face competition when and as they are approved and marketed. Our products may compete against products that have lower prices, established reimbursement, superior performance, are easier to administer, or that are otherwise competitive with our products. In addition, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors and there can be no guarantee of our ability to obtain or maintain patent protection for our products or product candidates. We cannot guarantee that we will be able to produce commercially successful products or maintain the commercial success of our existing products. Our stock price may be affected by actual or perceived market opportunity, competitive position, and success or failure of our products or product candidates. Further, the discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations.
The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration (FDA), and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Only the FDA can determine whether the product candidates are safe and effective for the use(s) being investigated. Further, the scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the FDA for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. Only the FDA can determine whether the products are safe and effective for these uses. Healthcare professionals should refer to and rely upon the FDA-approved labeling for the products, and not the information discussed in this news release.
SOURCE: Amgen
Post Views: 184
Preliminary Pre-Planned Interim Analysis Shows Negative Effect on Progression-Free Survival
THOUSAND OAKS, CA, USA | Mar 22, 2007 | Amgen (NASDAQ: AMGN) today announced that it has discontinued Vectibix(TM) (panitumumab) treatment in the PACCE trial evaluating the addition of Vectibix to standard chemotherapy and Avastin(R)(bevacizumab) for the treatment of first-line metastatic colorectal cancer (mCRC). The PACCE trial investigated a treatment regimen that used dual biologics combined with oxaliplatin- or irinotecan-based chemotherapy. This regimen is not currently used in clinical practice.
The decision to discontinue Vectibix treatment in the trial was based on a preliminary review of data from a pre-planned interim efficacy analysis scheduled after the first 231 events (death or disease progression). This analysis revealed a statistically significant difference in progression-free survival in favor of the control arm. An unplanned analysis of overall survival also demonstrated a statistically significant difference favoring the control arm. Additional analyses are ongoing, and Amgen plans to present the results at an upcoming scientific forum.
"Patient safety is Amgen’s top priority. For this reason, we have decided to discontinue Vectibix treatment in the PACCE trial while we complete additional analyses of these preliminary results. We had hoped that adding Vectibix to the current U.S. standard-of-care for patients newly-diagnosed with mCRC would improve outcomes without excessive added toxicity. Unfortunately, it appears that adding Vectibix to Avastin, when used in combination with oxaliplatin- or irinotecan-based chemotherapy, increased toxicity, without improving efficacy," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen.
Amgen has notified the FDA and study investigators that patients who are still receiving treatment in the PACCE study should discontinue Vectibix treatment. Patients will have the option of continuing per protocol treatment without Vectibix.
In January 2007, Amgen informed all investigators and regulatory authorities about safety information arising from a planned interim safety analysis of the PACCE trial. A review of the interim analysis showed an increased incidence of grade 3 severe events of diarrhea, dehydration and infections in the Vectibix-treated patients. In addition, an increased incidence of pulmonary embolism was observed in patients who received Vectibix compared with those who did not (4 percent and 2 percent, respectively). One (<1 percent) fatal event of pulmonary embolism occurred in a patient receiving Vectibix.
Amgen is continuing to explore Vectibix as a single biologic combined with chemotherapy in Phase 3 first- and second-line registrational trials. No other clinical studies are being modified at this time. However Amgen is evaluating data across all studies.
PACCE Study Design
The PACCE (Panitumumab Advanced Colorectal Cancer Evaluation) study is a Phase 3b randomized, open-label clinical trial evaluating oxaliplatin- and irinotecan-based chemotherapy and Avastin with and without Vectibix in the first-line treatment of patients with metastatic colorectal cancer. The trial is powered to show a 30 percent improvement in progression-free survival, the primary endpoint. Secondary endpoints include response rate, overall survival, duration of response and safety. The PACCE trial enrolled 1,054 patients (824 patients were randomized to receive oxaliplatin-based chemotherapy, and 230 patients were randomized to receive irinotecan-based chemotherapy) at 240 trial sites in the United States between Q1 2005 and Q3 2006.
About Vectibix
Vectibix is indicated for the treatment of patients with epidermal growth factor receptor- (EGFr) expressing metastatic colorectal cancer after disease progression on, or following fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens. The effectiveness of Vectibix for the treatment of EGFr-expressing, metastatic colorectal carcinoma is based on progression-free survival. Currently no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Vectibix.
Important Product Safety Information
Dermatologic toxicities, related to Vectibix blockade of EGF binding and subsequent inhibition of EGF receptor-mediated signaling pathways, included but were not limited to dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Dermatologic toxicities were reported in 89 percent of patients treated with Vectibix and were severe in 12 percent of patients. Severe dermatologic toxicities were complicated by infection, including sepsis, septic death, and abscesses requiring incisions and drainage. Vectibix may need to be withheld or discontinued for severe dermatologic toxicities.
Severe infusion reactions occurred with Vectibix in approximately 1 percent of patients. Severe infusion reactions were identified as anaphylactic reactions, bronchospasm, fever, chills, and hypotension. Although fatal infusion reactions have not been reported with Vectibix, they have occurred with other monoclonal antibody products. Severe infusion reactions require stopping the infusion and possibly permanently discontinuing Vectibix, depending on the severity and/or persistence of the reaction.
About Amgen
Amgen discovers, develops and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science’s promise by bringing safe, effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people’s lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
Forward Looking Statement
This news release contains forward-looking statements that involve significant risks and uncertainties, including those discussed below and others that can be found in Amgen’s Form 10-K for the year ended Dec. 31, 2006, and in Amgen’s periodic reports on Form 10-Q and Form 8-K. Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify side effects or manufacturing problems with our products after they are on the market.
In addition, sales of our products are affected by the availability of reimbursement and the reimbursement policies imposed by third party payors, including governments, private insurance plans and managed care providers, and may be affected by domestic and international trends toward managed care and healthcare cost containment as well as possible U.S. legislation affecting pharmaceutical pricing and reimbursement. Government regulations and reimbursement policies may affect the development, usage and pricing of our products. In addition, we compete with other companies with respect to some of our marketed products as well as for the discovery and development of new products. We believe that some of our newer products, product candidates or new indications for existing products, may face competition when and as they are approved and marketed. Our products may compete against products that have lower prices, established reimbursement, superior performance, are easier to administer, or that are otherwise competitive with our products. In addition, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors and there can be no guarantee of our ability to obtain or maintain patent protection for our products or product candidates. We cannot guarantee that we will be able to produce commercially successful products or maintain the commercial success of our existing products. Our stock price may be affected by actual or perceived market opportunity, competitive position, and success or failure of our products or product candidates. Further, the discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations.
The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration (FDA), and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Only the FDA can determine whether the product candidates are safe and effective for the use(s) being investigated. Further, the scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the FDA for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. Only the FDA can determine whether the products are safe and effective for these uses. Healthcare professionals should refer to and rely upon the FDA-approved labeling for the products, and not the information discussed in this news release.
SOURCE: Amgen
Post Views: 184
