Seattle Genetics, Millennium Nail 2nd Straight Trial With “Empowered Antibody” For Cancer

Xconomy Seattle — 

Seattle Genetics broke new ground in the field of cancer drug development last month, and now evidence is mounting from a second clinical trial that suggests it wasn’t a fluke.

Seattle Genetics (NASDAQ: SGEN) and its partner, Cambridge, MA-based Millennium: The Takeda Oncology Company, are reporting today that 50 out of 58 patients (86 percent) with a rare, deadly malignancy called anaplastic large cell lymphoma had complete or partial shrinkage of their tumors after taking their experimental “empowered antibody” drug in a clinical trial. Side effects associated with the drug, brentuximab vedotin (SGN-35), were consistent with prior studies. Full data for this study, and another groundbreaking trial of this drug for Hodgkin’s disease, will be presented at the American Society of Hematology annual meeting in Orlando, FL in December.

The results are eye-opening for a number of reasons. Patients who enrolled in this study had seen their disease worsen after at least one prior round of chemotherapy, meaning they had about a 25 percent chance of responding to another round of chemo, and a life expectancy of one to two years, says Seattle Genetics CEO Clay Siegall. While many cancer drugs only help one-fourth of patients, the new drug from Seattle Genetics has now shown an ability to shrink tumors in more than three-fourths of patients with two types of cancer—anaplastic large cell lymphoma and Hodgkin’s disease. Plus, patients in this study only got the Seattle Genetics drug by itself, which means they got the tumor shrinkage benefit without being subjected to the nasty side effects of chemotherapy. The data are compelling enough that Seattle Genetics plans to seek FDA clearance in the first half of 2011 to start selling the product for both forms of cancer.

“The data are superb,” Siegall says. “I’ve been doing this kind of work for 25 years, and data like this are what make it all worthwhile.”

Clay Siegall

Clay Siegall

About 2,000 adults in the U.S. each year are thought to have anaplastic large cell lymphoma, roughly 3 percent of the 65,540 people diagnosed with non-Hodgkin’s lymphoma in the U.S. each year.

While tumor shrinkage was the primary goal of this study, doctors will want to comb through the data that will come out in December in much greater detail. This study was designed to follow patients to see how long they stayed in remission, how long tumors were prevented from spreading, and how long patients actually lived. None of those important measurements are being made available in today’s announcement, and it will take more follow-up time to get those answers. Seattle Genetics also hasn’t said what proportion of patients had complete remission versus how many had partial remission. (That’s important, because doctors might be less impressed if the 86 percent response rate was achieved through 2 percent getting complete remissions, and 84 percent experiencing partial remissions).

Still, the data has important implications for more than just patients. It will help Seattle Genetics make a stronger case to the FDA to approve what could be the company’s first marketable cancer drug. Scientifically, it provides more evidence that says it’s a good idea to aim a targeted antibody drug against a protein found on cancer cells called CD30, which brentuximab vedotin is designed to hit. And it provides further validation for the new paradigm of “empowered antibodies” which seek to combine the precise targeting capability of an antibody drug, with super-potent toxins that have extra tumor-killing capability. Roche’s U.S.-based Genentech unit has released promising data for one such empowered antibody in the past year, but after it suffered a setback with the FDA, Seattle Genetics may now be in position to get its drug on the U.S. market first.

Millennium, through a partnership it struck a year ago, holds commercial rights to the product outside North America, where it says it plans to talk with regulators in Europe and other countries “as soon as possible” about how to bring the drug to market.

“We are thrilled to report these impressive data in this highly refractory patient population with a high unmet medical need,” said Nancy Simonian, Millennium’s chief medical officer, in a statement.

The markets for brentuximab vedotin so far are small. But because of the way the drug works against the CD30 target, Seattle Genetics is looking for other tumor types that also have a high number of those targets on their cell surface, which might make them vulnerable to brentuximab vedotin. The list of cancers Seattle Genetics is considering includes cutaneous lymphoma, peripheral T cell lymphoma, bone cancers, and diffuse large B-cell lymphoma, Siegall says. The drug, he says, has “much more” potential than just as a treatment for Hodgkin’s or anaplastic large cell lymphoma.

—Separately, Seattle Genetics also reported some other results from a study of another “empowered antibody” drug candidate in the works. This drug, SGN-75, is designed to hit a different protein target on cancer cells, called CD70.

Results from the first 16 patients who enrolled in this safety study are being presented today at the European Society of Medical Oncology meeting in Milan, Italy. Researchers there are reporting that one patient with non-Hodgkin’s lymphoma had tumors completely eradicated, while one more with kidney cancer (renal cell carcinoma) had a partial response. Those results were seen during the very initial phase of trials, when doctors are testing tiny doses to make sure they are safe, and gradually escalating doses to find the right balance of safety and effectiveness. That study hasn’t yet reached the maximum tolerated dose, which will inform the company about what its next step could be in clinical trials.

SGN-75 is still in its early development, so it’s premature to say it might offer patients hope. But it is following the same pattern, showing anti-tumor activity at less than optimal doses, which distinguished brentuximab vedotin in its early development. “We’re very excited about this one too, but it’s still early,” Siegall says.