It’s the season for playoff-level intensity for a bunch of Big Pharma and biotech companies. They’re all psyched up, over the next two weeks, to show clinical trial results for their drugs at the annual extravaganza for cancer doctors, put on by the American Society of Clinical Oncology (ASCO).
Win over those influential doctors, and you might gain some market share in an estimated $80 billion market for cancer drugs. Lose, and, like they say in the sports world, you can basically go home (or at least try to explain to investors why you lost and plan to mount a comeback next year).
If you’re Genentech, the South San Francisco-based unit of Roche, the world’s largest cancer drugmaker, then nobody has more at stake at this meeting than you. So as the abstracts go online this afternoon at the ASCO website, I took some time to chat with Philippe Bishop, the vice president of clinical development at Genentech, to get a read on the big studies that will compete for mindshare amid the frenzy of 30,000 doctors, investors, competitors, and journalists on hand at ASCO’s annual meeting in Chicago, June 3-7.
Headlines are firing like synapses all over the Internet as you read this, but most of the studies being presented at this year’s ASCO, like most in the past, will represent incremental progress at best. But this year Genentech says it is looking forward to touting some of the biggest advancements from its pipeline in a long time.
“We are a society that wants answers right away, in the big scheme of things,” Bishop says. “But the science is maturing, and we are seeing the fruits of that research. We’re beginning to see the results and true commitment that is behind these programs. We’ve been impatient in wanting results right away. It takes time.”
Here are a few themes that Genentech, and its legion of followers, will be focused on at ASCO:
—The hot new thing for melanoma that has spread through the body—vemurafenib. This drug, developed in partnership with Berkeley, CA-based Plexxikon under the code name PLX4032, has been all the rage in the oncology business the past year. Plexxikon made waves initially when it published early-stage trial results showing that more than 80 percent of patients experienced tumor shrinkage—a stunning result in a field where 10-15 percent response rates are more common. The evidence mounted a few months later, when Plexxikon and Genentech showed in a pivotal clinical trial of more than 600 patients that the drug was able to help patients live longer with a deadly form of skin cancer—as long as they were among the 50 percent of patients with a mutated protein known as BRAF.
Genentech, and the powers that be at ASCO, aren’t yet releasing critical details on how much longer patients lived longer on the new drug, how long their tumors remained in check, or what kind of side effect profile emerged in this pivotal study known as BRIM3. The big scoop is being saved for a press conference on Sunday June 5, and for a plenary presentation by Paul Chapman of Memorial Sloan-Kettering Cancer Center in New York.
It doesn’t take a genius to know this data is going to be big. Japan-based Daiichi Sankyo paid $805 million upfront to acquire Plexxikon after the BRIM3 results arrived, and it also took about a nanosecond in drug development time for Genentech to file an application to the FDA to start marketing the product.
There are a couple interesting points to note about this drug. The product is developed specifically for about half of melanoma patients (those with the mutated form of BRAF) and the trials were designed to use a companion diagnostic to screen out the patients who were unlikely to benefit. This is the sort of personalized medicine that Genentech popularized over a decade ago with trastuzumab (Herceptin), which has rarely been duplicated since. Now that insurers are increasingly balking at paying high prices for cancer drugs that only stand to help a small percentage of patients, Genentech is bound to play up the personalized aspect of this therapy in its meetings with doctors.
Also, look for plenty of questions about what happens when patients develop resistance to the heralded new drug. Genentech has noticed that a protein known as MEK is often overexpressed in patients who develop resistance to the BRAF inhibitor. So it has developed a new MEK inhibitor that it is testing in combination with the new Plexxikon drug, which it hopes will keep patients in remission for longer periods of time.
“This program highlights the power of the scientific group we have at Genentech,” Bishop says. “I’m excited about the biology we are learning from samples we’ve collected, and what we’re seeing in terms of clinical observation.”
—New opportunities for erlotinib (Tarceva). This is the drug for non-small cell lung cancer that has been put in a box of sorts, as a second- or third-line treatment—and one that doesn’t work for a majority of patients. The most benefit seen prior to this year’s ASCO has been seen in Asian populations.
Now Genentech is hoping to combat some of that perception with results from a new pivotal stage study, called EURTAC, which it says is the first to show the drug can be effective in patients getting their first round of treatment for lung cancer, and that it works for a Western population of people. The study, of more than 140 patients, randomly assigned patients to get either the Genentech drug by itself, or standard chemotherapy. The abstract of this study on the ASCO website is #7503, and the company says more data will come out at the meeting in early June.
“It’s an important finding,” Bishop says. “You have a targeted agent that is better than the standard of care for these patients.”
—While ASCO is a meeting mainly for clinicians who actually treat patients with cancer, it’s occasionally a showcase for stuff that a true scientist can appreciate. This will be the coming out party for something called MetMab, which is a one-armed antibody drug. Gene jockeys out there know that antibodies are Y-shaped genetically engineered proteins, with two arms, designed to bind specifically with a target found on cancer cells (and hopefully rarely found on any healthy cells).
In the case of certain forms of advanced lung cancer, scientists have been searching for a way to shut down the activity of a protein called MET. The big problem here, Bishop says, is that the way MET works, traditional two-arm antibodies that bind with it can get metabolized in a way that is thought to actually accelerate the activity of the biologic pathway—and make the cancer worse.
Since that’s probably not going to impress doctors or the FDA, Genentech’s engineers went to work on different protein structures that would shut down MET more effectively. That’s how they came up with a one-arm antibody.
The MET protein is thought to be a culprit in a number of cancers, but it’s particularly egregious in non-small cell lung cancer, Bishop says, so that’s where Genentech tested it first. The big study to watch at ASCO will be OAM4558G, highlighted in abstract #7505.
This trial was designed to enroll as many as 180 patients who were randomly assigned to get either a placebo or erlotinib (Tarceva) in tandem with MetMab. Importantly, researchers have been able to see that patients with MET mutations who got the MetMab did better than patients who low-level activity of MET, Bishop says.
“There’s some neat engineering here,” Bishop says.
Those are the big programs to watch, although Genentech will have plenty more to say, with more than 300 abstracts coming out online today about 30 different tumor types. There won’t be any major data presentations at this year’s meeting on a couple of Genentech’s high-profile antibody programs that we’ve covered here before—T-DM1 and pertuzumab.
For people who want more information on those drug programs for breast cancer, you’ll all just have to sit tight, and perhaps wait for another future ASCO. As Bishop says, everyone wants immediate results, but this cancer drug business takes time.
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