ASCO Preview: Seattle Genetics, ZymoGenetics, Trubion & Other Seattle Biotechs Offer Peeks at Cancer Drug Results
The market for cancer drugs is booming, on pace to grow from $66 billion in worldwide sales in 2008 to more than $84 billion by 2012, according to data from Cowen & Company. So if you are a member of the leading association of cancer physicians in the world, then chances are your annual meeting would be a pretty popular destination for members of the biotech and pharmaceutical industry, right?
There’s no doubt about it. The cancer-drug data frenzy known as the American Society of Clinical Oncology (ASCO) got its official kickoff of sorts as it released thousands of brief summaries, or abstracts, yesterday that serve as a preview of coming attractions at the group’s annual conference May 29 to June 2. This year’s meeting, to be held in sunny Orlando, FL, because it’s one of the few places with a big enough convention center, is expected to draw the usual crowd of 30,000 physicians, drug company executives, Wall Street analysts, and journalists who are seeking insights into what’s new and hot for the treatment of tumors.
Seattle-area companies have a historic strength in oncology, so this is a big moment for them to try to make a compelling case to physicians that they have drugs with real potential. Here are some of the highlights from local companies.
—Seattle Genetics. The Bothell, WA-based biotech company (NASDAQ: SGEN) said it plans to present data at the ASCO meeting from an early-stage clinical trial on how well its SGN-35 drug candidate (for lymphomas) performs when given on a weekly basis, instead of a less frequent schedule of once every three weeks.
This drug—which combines the tumor-targeting capability of an antibody with a potent toxin designed to give it extra killing power—has already shown stellar results when it is given once every three weeks. The previous trial was in 44 patients with relapsed forms of Hodgkin’s disease and related lymphomas who got the drug in that less-frequent dose. It showed that 17 of the 44, or about 38 percent, had their tumors completely wiped out.
The results with more frequent, weekly dosing are still quite preliminary, but they look even better. At the time the abstract was submitted, preliminary data showed that of the 15 patients taking low weekly doses, seven of them had a complete disappearance of their tumors, and one had more than 25 percent tumor shrinkage, Seattle Genetics said. Tumors stabilized in five patients, and just two had their disease spread or get worse. The drug was generally well-tolerated with the more intense weekly dosing, with some mild to moderate reports of rash, nausea, and nerve damage in the fingers and toes, the company said. More details will be presented at the conference on June 1.
—Seattle-based ZymoGenetics (NASDAQ: ZGEN) will present detailed results at ASCO on a mid-stage clinical trial of its experimental drug, IL-21, in combination with Bayer and Onyx Pharmaceuticals’ sorafenib (Nexavar). ZymoGenetics is hopeful that its drug, which is supposed to stimulate T cells and Natural Killer cells of the immune system to fight tumors, will add to the effect of sorafenib, which is made to cut off blood supply to tumors, and block pathways that allow those cells to proliferate.
The study, according to the abstract, enrolled 33 patients in the U.S. and Canada who failed to respond to one or two prior rounds of therapy for kidney cancer that has spread through the body. Six of the 23 evaluable patients (26 percent) had at least partial tumor shrinkage. Six patients dropped out of the study because of drug toxicity, and the regimen is clearly a rough one. One-third of patients reported moderate to severe side effects, including low phosphate levels, rash, and deficiencies of white blood cells and platelets in the blood. Researchers termed the safety profile “acceptable.”
“We see encouraging anti-tumor activity with IL-21 combined with Nexavar,” said Nicole Onetto, ZymoGenetics’ chief medical officer, in a statement. “We believe the combination of IL-21 and Nexavar could be more effective than Nexavar alone.” ZymoGenetics is looking to out-license this drug, because it is getting out of cancer research as part of the sweeping cost cuts it announced a couple weeks ago.
—Seattle-based Trubion Pharmaceuticals (NASDAQ: TRBN) reported that it plans to give a presentation on a clinical trial of its experimental cancer drug, TRU-016, at ASCO.
The drug is made through Trubion’s technology for targeting cells like an antibody, but using a smaller, lighter molecule that is supposed to be better at penetrating bulky tissues than larger antibody drugs. This trial looked at 10 patients with chronic lymphocytic leukemia who took an escalating series of doses of TRU-016. Researchers reported patients had decreasing counts of cancer cells in the blood after taking the drug, and it reduced their lymph nodes and spleen size. There were no serious adverse events, the company said.
“The data to be presented at ASCO expands our pre-clinical experience and reinforces our belief that TRU-016 has the potential to improve treatment options for patients with B-cell malignancies like chronic lymphocytic leukemia and non-Hodgkin’s lymphoma,” said Peter Thompson, Trubion’s CEO, in a statement.
—OncoGenex Pharmaceuticals, a Bothell, WA-based developer of cancer drugs, will finally relieve the suspense about its prostate cancer drug at the ASCO meeting. The company (NASDAQ: OGXI) made waves back in December when it reported results from a clinical trial of 82 men. The trial suggested the OncoGenex drug, OGX-011, had an unprecedented ability to help men live longer with the disease, a median time of 27.5 months on the company’s experimental drug in combination with a chemo treatment and immune suppressor, compared with 16.9 months for those on the latter two treatments alone.
But skeptics now have some ammunition to shoot holes in this result. The company never disclosed in its press release back in December whether the survival finding reached the FDA’s threshold to show it was statistically significant, and therefore unlikely to be due to chance. That threshold is a p-value of 0.05 or lower. The OGX-011 study, as you can see in this abstract, had a p-value higher than that, 0.07.
OncoGenex is hoping that investors and partners won’t be scared away by that uncertainty, pointing out that the study’s primary goal wasn’t to show improved survival times, and it is extremely difficult, in a mathematical sense, to achieve statistical significance in a small study of 82 patients, said Jason Spark, a spokesman for the company. Plus, this isn’t the final word on the study, because the abstract uses relatively old data from November, while the formal presentation at ASCO will provide more follow-up data needed for the final analysis—which may produce a different p-value, Spark says.
The drug is interesting to scientists because it uses “antisense” technology, essentially designed to serve like a genetic mirror image that shuts down the production of clusterin, a protein associated with helping tumors resist chemotherapy. The original work was done by Martin Gleave, a urologist at the Prostate Centre Vancouver General Hospital. OncoGenex hopes the ASCO presentation will generate enough interest from potential partners, and investors, to raise enough money to complete a pair of pivotal clinical trials, with more than 700 men, which it will need to win FDA approval of the product.
—Cell Therapeutics (NASDAQ: CTIC) will present data on its experimental drug for non-Hodgkin’s lymphoma, pixantrone. Nothing much new appears in the abstract—the Seattle-based company repeated that a study called PIX-301 of 140 patients found that 20 percent of those randomly assigned to get the drug had their tumors completely disappear, compared with 5.7 percent who did that well in a control group. These patients were quite sick, having failed to respond to at least two prior rounds of therapy.
Pixantrone is modified to be less toxic to the heart than other drugs in the anthracycline class of chemotherapies. The trial was originally designed to enroll 320 patients, but was cut down to 140 because of slow enrollment. The company disclosed in its annual report that there were more “severe cardiac events” among patients who got the drug, than in the control group.
—Calistoga Pharmaceuticals, the Seattle-based biotech company that raised $30 million in venture funding this month, will offer an early peek at its cancer drug data at ASCO.
The company’s drug, CAL-101, is made to block a target on cells known as the PI3 kinase that controls tumor formation and metabolism, and is one of the hottest in cancer biology at the moment. Preliminary data to be presented at ASCO shows that six patients got the drug, an oral pill, twice a day at low doses for relapsed forms of chronic lymphocytic leukemia or select types of non-Hodgkin’s lymphoma. Two of the six patients had at least partial tumor shrinkage, and the other four had their tumors stabilize, researchers said. No moderate or severe side effects were reported, researchers said. More updated data will be available at the meeting.
A study of eight patients with liver cancer tested the company’s Litx therapy, in which patients get an inert small-molecule drug, talaporfin sodium, that is activated when a doctor sticks a catheter with a light emitting diode into a tumor. One of the eight patients had their tumors completely disappear after the procedure, another five had their disease stabilize, and two had their tumors spread. There were no moderate or severe adverse events in the study, researchers said. This finding will have to be reproduced in a larger, pivotal trial that is nearing completion, researchers said.
—Alder Biopharmaceuticals, a Bothell, WA-based company that seeks to make better antibody drugs in yeast, presented some Phase I clinical trial data on ALD518 for patients with advanced cancer. This drug is also being developed as a treatment for rheumatoid arthritis.
The drug, which is made to hit a target on cells called IL-6, is being developed to block excess inflammatory cells that contribute to extreme fatigue in cancer patients, and muscle atrophy known as cachexia. The study of nine patients looked at an intravenous infusion of the Alder drug at three different doses. Just five of the patients completed all the visits called for by the study protocol, while three withdrew as their tumors worsened. There were no severe side effects reported, and the drug was able to reverse fatigue in this small study, researchers said.