Onyx Pharmaceuticals Inc. and partner Bayer Healthcare Pharmaceuticals Inc. reported detailed results from their positive Phase III trial of Nexavar (sorafenib) in liver cancer, which has emerged as one of the biggest headlines at this year's American Society of Clinical Oncology meeting in Chicago.
The annual conference highlighted many successful mid-stage and late-stage products, such as Poniard Pharmaceutical Inc.'s picoplatin in non-small-cell lung cancer and IDM Pharma Inc.'s cancer vaccine, EP-201, also in NSCLC, but like years past, it was the industry's big name products that garnered the most attention. Those included Onxy's and Bayer's oral multi-kinase inhibitor, as the first drug shown to improve survival in patients with advanced liver cancer.
While the results were hardly unexpected - the companies' reported interim results in February showing that the pivotal study met its endpoint of improvement in overall survival earlier than expected - the more detailed data released Monday showed a 44 percent increase in overall survival in patients receiving Nexavar compared to placebo. Median overall survival was 10.7 months in the Nexavar-treated group vs. 7.9 months in the placebo group, a relatively significant improvement in a condition for which there are no existing therapies that extend survival. Those data pushed Onxy's (NASDAQ:ONXX) stock up about 8.55 percent Monday to close at $33.52.
The companies began the Phase III study in March 2005 and anticipated enrolling about 500 previously untreated patients, with the trial expected to conclude in the second half of this year. However, the promising interim efficacy data prompted the trial's data monitoring committee to recommend an early halt to the trial. That news sent the company's stock soaring nearly 100 percent to close at $24.15 in February. (See BioWorld Today, Feb. 13, 2007.)
Nexavar, which is designed to target both the tumor cell and tumor vasculature, previously gained approval for kidney cancer. For the first quarter, the drug pulled in net revenues of $60.9 million. Onyx and Bayer are preparing to file for regulatory approval to expand Nexavar's use into liver cancer, based on the recent Phase III data, and if approved, the compound has been estimated to reach peak sales of $150 million to $300 million in that indication.
Under the terms of the companies' collaboration, Onyx is funding 50 percent of Nexavar's development costs, in exchange for a 50/50 profit share in the U.S. and a lesser share in the rest of the world, except for Japan. In Japan, Bayer funds all product development, and Onyx is entitled to royalties.
Avastin Works At Lower Doses In NSCLC
Several abstracts coming out of this year's ASCO meeting centered on South San Francisco-based Genentech Inc.'s blockbuster cancer drug, Avastin. The biotech giant reported results from several studies of the anti-angiogenic compound, including data from the anticipated 1,044-patient AVAiL study, which indicated that the drug might work better if given at a dose lower than the 15 mg/kg approved last year for treating metastatic non-small-cell lung cancer.
The study, sponsored by partner Basel, Switzerland-based F. Hoffmann-La Roche Ltd. demonstrated that Avastin (bevacizumab), significantly increased progression-free survival in advanced non-small-cell lung cancer patients at both doses tested in combination with chemotherapy, but that patients receiving the lesser dose, 7.5 mg/kg, showed greater improvement (33 percent) than those receiving 15 mg/kg (22 percent) over the chemotherapy-only arm. If physicians start prescribing at that lower dosage, Genentech could see a reduction in projected sales figures in that indication, though analyst Joel Sendek, of Lazard Capital Markets, maintained a "buy" rating, and wrote in a research note that any decline in dosage as a result of the AVAiL data "will be offset by an increase in duration of use and penetration as a result of an improved safety profile and confirmatory trial."
Separate presentations showed Avastin's promise in combination therapy. Results from a Phase III trial testing the antibody drug in combination with interferon alpha-2a therapy showed positive results in progression-free survival in patients with metastatic renal-cell carcinoma. Patients showed a 59 percent improvement compared to those receiving interferon alpha-2a therapy alone, and those receiving both treatments had a median PFS of 10.2 months, compared to 5.4 months for those in the interferon-only arm. And results from another study, the Phase II XCALIBr (Xeloda in Combination with Avastin as First-Line Treatment for HER2-Negative Metastatic Breast Cancer) trial, showed that a combination of the two drugs delayed time to disease progression by a median of 5.7 months overall in patients with no prior history of treatment. A subset of women in the XCALIBr study with advanced estrogen receptor positive breast cancer demonstrated a median delay of 8.9 months.
In addition to Avastin data, Genentech also reported updated results from a joint analysis of two Phase III studies of Herceptin (trastuzumab) for the adjuvant treatment of HER2-positive breast cancer, which showed that, with median follow-up of nearly three years, the addition of Herceptin to standard adjuvant therapy, significantly improved overall survival, compared to standard adjuvant therapy alone. Patients who received Herceptin had a 52 percent reduced risk of breast cancer recurrence compared to standard treatment alone, and at four years of follow-up, 85.9 percent of women treated with Herceptin plus chemotherapy were disease-free vs. 73.1 percent of those receiving chemotherapy alone.
The company also reported results of several investigational products. Pertuzumab, a monoclonal antibody designed to bind to the HER2 receptor, demonstrated an increase in overall progression-free survival by 52 percent when combined with gemcitabine in a Phase II trial involving patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancers.
In a separate Phase II study, pertuzumab, in combination with Herceptin, showed encouraging results in objective response rate in women with HER2-positive metastatic breast cancer whose disease had progressed following previous treatment with Herceptin and chemotherapy. Results from a Phase I study of apomab, the company's human DR5 agonist antibody, in 23 patients with advanced or metastatic solid tumors or non-Hodgkin's lymphoma indicated that that the product was tolerated at the five dose levels tested and that 52 percent of the patients experienced stable disease.
Shares of Genentech (NYSE:DNA) closed at $77.95 Monday, down $1.55.
In other ASCO news:
• ArQule Inc., of Woburn, Mass., reported Phase I data showing that ARQ 197, its selective inhibitor of the c-Met receptor tyrosine kinase, was well tolerated over extended dosing periods, with more than 60 percent of patients experiencing partial responses, minor responses or stable disease. Findings resulted in a recommended Phase II dose of 240 mg daily.
• Cyclacel Pharmaceuticals Inc., of Berkeley Heights, N.J., said interim results from a Phase I trial of sapacitabine (CYC682), an oral nucleoside analogue, demonstrated a favorable safety profile and promising anti-leukemic activity in patients with relapsed and refractory acute myelogenous leukemia and myelodysplastic syndromes. Eleven of 21 patients showed a decrease of more than 50 percent in bone marrow blasts, including seven patients with blast reduction to 5 percent or less.
• Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., and Sanofi-aventis, of Paris, reported preliminary results from two Phase II studies of aflibercept (VEFG Trap), its anti-angiogenic agent, in ovarian cancer, showing an 8 percent partial response rate and 77 percent achievement of stable disease in heavily pretreated patients who have failed multiple other treatments. While those results were encouraging, analysts clearly had been expecting more impressive data. Shares of Regeneron (NASDAQ:REGN) dropped $2.68, or 11.7 percent, Monday to close at $20.31.