Genentech Reveals Encouraging Avastin Data Bayer`s Nexavar Gets FDA Approval For Liver Cancer - Update [DNA]
Posted on: 11/19/2007
Genentech Reveals Encouraging Avastin Data; Bayer's Nexavar Gets FDA Approval For Liver Cancer - Update [DNA]
11/19/2007 11:19:39 AM Monday morning, biotechnology company Genentech Inc. (DNA) announced that its cancer drug Avastin showed encouraging results in a Phase II study in treatment of patients with the most aggressive form of brain cancer, over a six-month period. The company said that the findings exceeded its expectations and it plans to discuss next steps with the U.S. Food and Drug administration or FDA. Meanwhile, another biopharmaceutical company Onyx Pharmaceuticals Inc. (ONXX), along with Bayer HealthCare Pharmaceuticals Inc., announced that the FDA approved a supplemental New Drug Application for their oral anticancer drug Nexavar for the treatment of patients with unresectable hepatocellular carcinoma or liver cancer. The drug has already been approved for treatment of patients with advanced kidney cancer.
Avastin, or bevacizumab, is a therapeutic antibody designed to specifically inhibit vascular endothelial growth factor or VEGF, a protein that plays a major role in angiogenesis and the maintenance of existing blood vessels throughout the life cycle of a tumor. By inhibiting VEGF, Avastin is designed to interfere with the blood supply to a tumor, which is thought to be critical to a tumor's ability to grow and spread in the body.
San Francisco, California-based Genentech, which is majority owned by Swiss drug maker Roche Holding AG, said that both study arms of a randomized, multi-center Phase II clinical study of Avastin administered alone or in combination with irinotecan chemotherapy demonstrated encouraging six-month progression-free survival and objective response in patients with relapsed glioblastoma multiforme or GBM, the most common and aggressive type of brain cancer.
Genentech said that the study was a Phase II, open-label, multicenter, randomized, non-comparative study, which enrolled 167 patients with GBM whose cancer had relapsed after first- or second-line therapy. The company said that all patients had received prior temozolimide. Patients were randomized to receive Avastin alone or in combination with irinotecan every other week for up to 104 weeks.
The primary end points were six-month PFS and objective response rate as determined by an Independent Radiology Facility. PFS was defined as the absence of any event of cancer progression or death. Secondary endpoints of the study included overall survival and safety. Genentech noted that the study is ongoing and final analyses for safety and other efficacy endpoints will be available in 2008.
Genentech said that as assessed by independent radiological review, 36% of patients treated with Avastin alone, and 51% of patients treated with Avastin in combination with chemotherapy, lived without the disease advancing within six months. Further, the company noted that no new or unexpected safety events related to Avastin were observed in the study.
The company noted that in addition to six-month progression free survival or PFS rates of 36% and 51% respectively in the Avastin-alone and Avastin plus chemotherapy arms, preliminary estimates of tumor response were observed in 21% of patients treated with Avastin alone and in 34% of patients treated with Avastin in combination with chemotherapy.
Timothy Cloughesy, Director, Neuro-Oncology Program of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles and lead investigator for the study said, “Historical estimates suggest that only 15% of patients with this aggressive type of brain cancer live without their cancer progressing within six months. The findings suggested that at six months, more patients had lived without their cancer advancing when Avastin was administered as a single-agent or in combination with chemotherapy, than what we would normally expect.”
Hal Barron, senior vice president, Development and chief medical officer of Genentech said, “These findings exceeded our expectations, and due to the high unmet medical need of patients with relapsed GBM, we plan to discuss these data with the FDA to determine next steps.”
Genentech noted that adverse events related to Avastin in the trial appeared to be similar to those previously reported in other studies of Avastin. The most common severe toxicities in the Avastin alone arm were hypertension and convulsion, while the most common severe adverse events in the Avastin plus chemotherapy arm were convulsion and neutropenia. Grade 1 and 3 intracranial hemorrhage occurred in two patients in the Avastin arm alone, while one patient in the Avastin plus chemotherapy arm experienced a Grade 4 intracranial hemorrhage. In addition, two deaths were associated with adverse events in the Avastin arm alone and one death was associated with an adverse event in the Avastin plus chemotherapy arm.
Avastin was first approved by FDA in February 2004 as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy and is also indicated in combination with intravenous 5-FU-based chemotherapy for second-line treatment of patients with metastatic carcinoma of the colon or rectum. In October 2006, the FDA approved Avastin in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic, non-squamous, non-small cell lung cancer.
According to the American Cancer Society or ACS, the five-year survival rate for patients with GBM is 3% and has not changed in more than 25 years. The ACS estimates that there will be 20,500 new cases of brain cancer and 12,740 brain cancer deaths in 2007.
In the recently concluded third quarter, Avastin recorded sales of $597 million, representing an increase of 37% over the year-ago period. At that time, Genentech announced that it completed enrollment in the late stage first-line HER2-negative metastatic breast cancer study RIBBON-1, evaluating physicians' choice of chemotherapy with Avastin. Additionally, Genentech commenced enrollment in a Phase III combination study of Rituxan and Avastin in first-line diffuse large B-cell lymphoma and a Phase II combination study of Avastin and sunitinib malate in renal cell carcinoma.
In October, Genentech said that it would ban direct purchases of Avastin by independent compounding pharmacies, effective November 30, as a low-cost substitute for its eye drug, Lucentis. Avastin is chemically similar to Lucentis. However cancer drug Avastin is not approved for ocular uses and is not manufactured to meet U.S. Pharmacopoeia ophthalmic standards.
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