First shot on lung cancer goal goes wide:
>>Bayer and Onyx Provide Update on Phase 3 Trial of Nexavar in Patients With Non-Small Cell Lung Cancer
Monday February 18, 10:00 am ET
WAYNE, N.J. and EMERYVILLE, Calif., Feb. 18 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX - News) today announced that a Phase 3 trial evaluating Nexavar® (sorafenib) tablets in patients with non-small cell lung cancer (NSCLC) was stopped early following a planned interim analysis, when the independent Data Monitoring Committee (DMC) concluded that the study would not meet its primary endpoint of improved overall survival. The Phase 3 ESCAPE (Evaluation of Sorafenib, Carboplatin And Paclitaxel Efficacy in NSCLC) trial evaluated Nexavar when administered in combination with the chemotherapeutic agents carboplatin and paclitaxel in patients with non-small cell lung cancer (NSCLC). Safety events were generally consistent with those previously reported. However, higher mortality was observed in the subset of patients with squamous cell carcinoma of the lung treated with sorafenib and carboplatin and paclitaxel versus those treated with carboplatin and paclitaxel alone.
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Bayer and Onyx are providing information regarding this DMC recommendation to health authorities and those clinical investigators involved in studies of Nexavar. In addition, the companies will further review the findings of this analysis and DMC recommendation to determine what, if any, impact they have on other ongoing Nexavar lung cancer trials. Data from this study will be presented at an upcoming scientific meeting.
"While we are disappointed in this outcome, Bayer and Onyx remain committed to our comprehensive pan-tumor clinical trial program for Nexavar. Nexavar has proven significant clinical benefit for patients with liver cancer and advanced kidney cancer and we will continue to investigate its potential across a wide variety of tumors," said Susan Kelley, MD, vice president, Therapeutic Area Oncology, Bayer HealthCare Pharmaceuticals.
ESCAPE Trial Design
This multicenter, randomized, double-blind, placebo-controlled Phase 3 study enrolled more than 900 patients with non-small cell lung cancer at more than 140 clinical sites in North America, South America, Europe and the Asia Pacific region. The primary endpoint was overall survival, and secondary endpoints included progression-free survival, tumor response, patient quality of life and safety. Participating patients had not received any prior systemic anti-cancer treatment for their lung cancer and enrollment was open to patients with all histologies (or cell types) of NSCLC, including those with squamous cell carcinoma or adenocarcinomas.
Patients were randomized to receive 400 mg of oral Nexavar twice daily or placebo, in addition to two chemotherapeutic agents -- carboplatin and paclitaxel -- for up to six cycles. Subsequently, patients continued in a maintenance phase where Nexavar or placebo was administered as a single agent until study drug was discontinued due to progression of tumor or side effects.
Comprehensive NSCLC Program
Bayer and Onyx have a comprehensive program of clinical trials studying Nexavar for the treatment of NSCLC in a variety of patient populations and in combination with other anti-cancer regimens. These include a second ongoing Phase 3 study, known as NExUS (NSCLC research Experience Utilizing Sorafenib), in previously untreated patients, administering Nexavar in combination with two chemotherapeutics commonly used in Europe, gemcitabine and cisplatin. In addition, a Phase 2 trial sponsored by a cooperative study group in the United States in patients who have failed two or more therapeutic regimens has also completed enrollment. There are also multiple Phase 2 studies in patients who have experienced disease progression despite treatment with one prior therapeutic regimen.
Nexavar's Differentiated Mechanism
Nexavar targets both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to target members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) -- two important processes that enable cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET.
Nexavar is currently approved in more than 30 countries for liver cancer and in more than 60 countries for the treatment of patients with advanced kidney cancer. Nexavar is also being evaluated by the companies, international study groups, government agencies and individual investigators as a single agent or combination treatment in a wide range of other cancers, including metastatic melanoma, breast cancer and as an adjuvant therapy for kidney cancer and liver cancer.
Important Safety Considerations For Patients Taking Nexavar
Based on the currently approved U.S. package insert for the treatment of patients with unresectable hepatocellular carcinoma, hypertension may occur early in the course of therapy and blood pressure should be monitored weekly during the first six weeks of therapy and treated as needed. Bleeding with a fatal outcome from any site was reported in 2.4% for Nexavar and 4% in placebo. The incidence of treatment-emergent cardiac ischemia/infarction was 2.7% for Nexavar vs. 1.3% for placebo. Most common adverse events reported with Nexavar in patients with unresectable HCC were diarrhea, fatigue, abdominal pain, weight loss, anorexia, nausea and hand-foot skin reaction. Grade 3/4 adverse events were 45% for Nexavar vs. 32% for placebo. Women of child-bearing potential should be advised to avoid becoming pregnant and advised against breast-feeding. In cases of any severe or persistent side effects, temporary treatment interruption, dose modification or permanent discontinuation should be considered.
For information about Nexavar including U.S. Nexavar prescribing information, visit nexavar.com or call 1.866.NEXAVAR (1.866.639.2827).<<
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Given that the data to date wasn't too impressive, I don't think the Street had high expectations in any lung cancer trial. It could be the severe reaction today has to do with Onxx continuing in that direction, but aren't most of the trials funded by means other than ONXX' cash? Perhaps also adding to today's slide and failure to rebound much, is the lack of '08 guidance. Earnings were lower than expected, as well, so a multiple whack here.
>>UPDATE 2-Onyx shares plunge after drug fails in lung cancer
Tue Feb 19, 2008 9:34am EST
BOSTON, Feb 19 (Reuters) - Shares of Onyx Pharmaceuticals Inc (ONXX.O: Quote, Profile, Research) fell 20 percent on Tuesday after a trial showed its liver and kidney cancer drug failed to help patients with lung cancer.
On Monday, Onyx and its German partner, Bayer AG (BAYG.DE: Quote, Profile, Research), said they had stopped a late-stage trial of the drug, Nexavar, after an independent data-monitoring committee found the trial would not show an improvement in overall patient survival.
The trial tested Nexavar in combination with the chemotherapy agents carboplatin and paclitaxel in patients with non-small cell lung cancer (NSCLC), the most common form of the disease. Nexavar is Onyx's only product.
Howard Liang, an analyst at Leerink Swann, said, "While we believe the stock had only priced in limited expectations of a positive interim analysis, the early termination for lack of efficacy was not expected."
Shares of ImClone Systems Inc (IMCL.O: Quote, Profile, Research), which hopes to win approval for its cancer drug Erbitux to be used against lung cancer, rose 5 percent in early trading. Shares of Genentech Inc (DNA.N: Quote, Profile, Research) and OSI Pharmaceuticals Inc (OSIP.O: Quote, Profile, Research) which market the cancer drug Tarceva for lung cancer, also rose. The Genentech drug Avastin is also used for lung cancer.
"In our view, the failure of Nexavar in non-small cell lung cancer is a significant positive for Genentech and OSI Pharma as it removes a major potential competitor in the NSCLC market," Geoffrey Meacham, an analyst at JP Morgan, said in a report. "ImClone is also a beneficiary, but data showing the benefit of Erbitux in NSCLC has not been revealed."
Nexavar, also known as sorafenib, is approved in the United States and Europe for use against kidney cancer and liver cancer. Onyx and Bayer are studying the drug for treatment of a broad range of cancers, including breast cancer.
Under the terms of the collaboration, the companies share all research and development, marketing, and non-U.S. sales expenses.
Onyx on Tuesday reported a fourth-quarter net loss of $11.7 million, or 21 cents a share, compared with a net loss of $20.7 million, or 47 cents a share, a year earlier.
Analysts' average forecast was a loss of 7 cents a share, according to Reuters Estimates.
Net sales of Nexavar nearly doubled to $124.9 million in the quarter. For the year, sale of the drug totaled $371.7 million.
Onyx said the net amount due from Bayer was $4.4 million in the quarter.
Onyx shares were down $9.19 at $45.79 in early trade on Nasdaq. (Reporting by Toni Clarke; additional reporting by Jennifer Robin Raj in Bangalore; editing by Pratish Narayanan and John Wallace)<<
A smidgen more analyst color can be found here:
notablecalls.blogspot.com
How much more unexpected bad news can there be? I've bought a slug of calls, but am a bit under water at the moment.
Cheers, Tuck |
