Each spring, everybody and their brother in biotech goes to the American Society of Clinical Oncology (ASCO) annual meeting to check out the hot new stuff in cancer drug development. But for Cambridge, MA-based Millennium: The Takeda Oncology Company, the bigger medical meeting is coming up this weekend, where a whole string of clinical trials will be unveiled that could alter fortunes and change the way doctors treat specific malignancies that lurk in the blood.
Millennium and its partners and competitors will gather this weekend for the American Society of Hematology (ASH) conference in Orlando, FL, to woo the influential physicians who can anoint the top new products for treating blood disorders and blood cancers. About 20,000 people are expected to attend this conference, many of them looking for the next big thing in the treatment of rare leukemias, lymphomas, and myelomas.
Millennium is a mainstay at this meeting, having developed a $1 billion hit molecule in bortezomib (Velcade) for multiple myeloma. Japan-based Takeda Pharmaceuticals paid $8.8 billion to acquire Millennium in 2008. So the big question for Millennium now is how it can continue to keep the momentum going for its one big hit, and what else it has in the pipeline to represent future growth. The company surely will also be keeping a close eye on its competitors, including Emeryville, CA-based Onyx Pharmaceuticals (NASDAQ: ONXX). Onyx is expected to release clinical trial data on a drug that seeks to help patients with myeloma even after they stop responding to the Millennium drug. I plan to report on that drug, carfilzomib, separately on Xconomy’s San Francisco site.
I caught up with Millennium’s chief medical officer, Nancy Simonian, by phone right before Thanksgiving to get a sense of what themes to watch for at the upcoming ASH meeting. She was pumped right off the bat. “It’s going to be a pretty exciting ASH,” she said. Here are three main themes we talked about.
—Velcade as a maintenance therapy. “When you as a patient present with myeloma-one of the major goals with initial treatment is to get the tumor burden down,” Simonian says. That means there’s a strong rationale for an intense upfront dosing schedule, which shows quick anti-tumor results.
What doctors don’t know as much about is what happens later, after the tumor is shrunk. What is the best way to structure a low-dose maintenance regimen, to keep the tumors from coming back? How can you do this to make sure the drug won’t increase nerve damage in the fingers and toes—a known side effect of the Millennium product. There is no consensus on this approach, and what might be the best dosing schedule, Simonian says. But obviously, since patients are living longer, if Millennium can sell consistent amounts of the drug to patients over a longer period of time, that would translate into more sales.
“The important thing emerging is how can we think about giving it in a way that maximizes the benefit and minimizes the intolerability,” Simonian says.
There are a couple of studies to watch in particular about Velcade in the maintenance setting. One, called Hovon, will be presented Sunday, Dec. 5 at 5:15 pm Eastern. The second, called Upfront, will come out Monday Dec. 6 at 2:45 pm Eastern.
—The “empowered antibody” against lymphomas. This is a drug developed by Seattle Genetics, known as SGN-35 or brentuximab vedotin. It’s an antibody designed to seek out specific cancer cells, while being combined with a potent dose of chemotherapy to give the package extra tumor-killing kick. Seattle Genetics (NASDAQ: SGEN) retains complete commercial rights to this drug in North America, but Millennium has obtained the rights in Europe and other parts of the world. The companies have already told investors that this drug hit its tumor shrinkage goals in studies of patients with relapsed forms of Hodgkin’s disease and anaplastic large cell lymphoma.
The results of the studies were remarkable—about 75 percent of Hodgkin’s patients had their tumors shrink, while 86 percent of anaplastic large cell lymphoma patients did that well. If the drug had performed that well for 30 percent of patients, it would have been good enough to take to the FDA for approval. But the main questions Seattle Genetics and Millennium will get at ASH are the kind that companies dream of fielding: How many patients had complete remissions versus partial remissions? How long did the remissions last? How does that square with the side effect profile? How long did patients actually live on the drug, compared with their life expectancy on standard meds? (It’s still too early to answer that one).
The big presentation of this drug in Hodgkin’s patients will be at 7 am Eastern on Monday Dec. 7, while the anaplastic large cell lymphoma talk will come later, at 7:30 am on Tuesday, Dec. 8.
“The overall response rate was very impressive. To see that level of activity in patients who don’t have a lot of other options, it’s very exciting. It will be a really important overall finding at ASH,” Simonian says.
—What else is coming in the Millennium pipeline? Ever since the Takeda takeover, Millennium has been set up to be the company’s global center for cancer R&D, which ultimately means it will be judged on whether it can deliver more drugs like Velcade and brentuximab vedotin to the marketplace. Millennium CEO Deborah Dunsire and other executives talked in some detail about this in an R&D overview in Japan back in March 2009.
One of those drugs highlighted back then, MLN-4924, is starting to show enough early signs of activity to get a hearing on the big stage of ASH. This drug, as I described back then, blocks the Nedd8 activating enzyme, a novel target discovered by Millennium scientists. This small-molecule drug is supposed to block pathways that are critical to cancer cell growth and survival.
Researchers are expected to present data from the first of three phases of clinical trials generally required for FDA approval, so this one is still at an early stage of the game. Its key data will come at 7 am Eastern on Monday Dec. 6.
“There’s very novel biology here, there’s biomarker work built into the study, and there are already signs of activity in patients with AML (acute myeloid leukemia). You’ll be hearing a lot about that,” Simonian says.
A little science background is required to understand why this matters. Velcade is what’s known as a proteasome inhibitor, which showed that if you can make a drug to inhibit these enzymes (which act as a cellular garbage disposal), then you might block the release of certain proteins that cancer cells secrete to grow and resist conventional chemotherapies. The new Millennium molecule is seeking to build on this philosophy, approaching it from a slightly different angle.
“It’s a new way to think about treating cancer—going after the infrastructure,” Simonian says. Rather than just focusing on mutations that stand out as specific targets on tumors, Millennium is looking at how the cell adapts to survive or regulate itself while under enhanced stress from something like chemotherapy. A slight change on how those proteins function may be enough to coax the cancer cell into a state of self-destruction, known as apoptosis, Simonian says.
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