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Genentech Aims to Set Precedent With FDA OK in Early Breast Cancer

Xconomy San Francisco — 

Exactly when does it make sense to start giving breast cancer patients one of the most potent, targeted drugs that doctors have in their repertoire?

That’s the gist of a question that an FDA panel of cancer drug experts will consider on Thursday, when they review an application from South San Francisco-based Genentech, a unit of Switzerland-based Roche. On the surface, the company is simply asking the FDA for clearance to start selling one of its targeted antibody drugs to women with locally confined breast cancer that overexpresses the HER2 protein, and who haven’t yet had surgery to remove breast tumors. This would be a first, as there currently are no FDA-approved drugs in this group of women, who are sometimes called “neoadjuvant” or “preoperative” patients.

The question might sound like a narrow one of medical interest, but it has bigger implications for Genentech and the biotech industry. For Genentech, a yes from the FDA would obviously open the door to a larger potential market for pertuzumab (Perjeta), a targeted drug that won FDA approval last year for a sicker group of patients who have breast cancer that has spread.

But this application is really about more than just one drug in one big company’s portfolio. If Genentech gets its way, it could change the way the company and others think about developing cancer drugs, enabling them to consider clinical trials that are faster, cheaper, and smaller. Put another way, the FDA will be signaling that, in certain circumstances, it is willing to approve new cancer drugs without forcing companies to make huge investments in time and money to gather proof from large studies that they keep tumors in check for a few extra months, or ultimately help patients live longer.

“We are setting a precedent,” says Dietmar Berger, Genentech’s vice president of clinical oncology. “We very much welcome that FDA is using this type of innovation. What we’re trying to do is bring a drug to patients, but to get the right amount of efficacy and safety information that you need.”

Essentially, the FDA panel on Thursday will be a referendum of sorts on how much faith the agency is willing to put in a leading indicator of patient prognosis called pathological complete response (pCR). In the case of this Genentech drug, the company gathered that data, on the percentage of patients who appeared free of cancer, between nine and 18 weeks after they entered a clinical trial. While that kind of result should logically give a patient a better future, no one can say for sure if that early positive sign translates into a long-term improvement in survival time and quality of life.

If the FDA says that the pCR measurement is valid, you can be sure many other companies will try to design trials to hit that goal for other kinds of cancer. Trials of this nature could save companies months, or even years, in development, and millions and millions of dollars.

FDA staff released their own briefing document for the Oncologic Drugs Advisory Committee online yesterday, and it was a pretty straightforward and positive summary of Genentech’s dataset. The drug in question, pertuzumab (Perjeta), was first approved in June 2012 for women with breast cancer that overexpresses the HER2 protein, and which has spread through the body. It’s approved in combination with Genentech’s other HER2-directed antibody, trastuzumab (Herceptin) and chemotherapy. The drug generated about 108 million Swiss francs in sales during the first half of 2013, which translates to about $115 million at today’s currency conversion rates.

Last year when the drug was approved by the FDA, it was primarily on the basis of a study called Cleopatra. That study, of 808 women, showed that when pertuzumab was added to the other antibody and chemotherapy, it was able to keep tumors from spreading for an additional six months, without adding significant side effects.

That study was good enough to get pertuzumab on the market, but it wasn’t the only trial where the product showed promise. The drug, which looked like a loser back in 2005, was revived five years later by the results of a study known as Neosphere. That trial looked at 417 women with HER2-overexpressing tumors, who were still in the early, preoperative stage of disease, with “neoadjuvant” status. Researchers found that 39.3 percent of women randomly assigned to get pertuzumab, trastuzumab and chemo achieved a pathological complete response, compared with 21.5 percent who did that well on the original trastuzumab and chemo alone. The difference was statistically significant, meaning it was unlikely due to chance.

The FDA has tried to do its own analysis of a variety of clinical trials that enrolled a total of 12,000 patients with neoadjuvant status, to see whether pathological complete response truly indicates a patient is on track for a better long-term outcome. As it notes in this week’s briefing document, the analysis was discussed at some length in a workshop with industry representatives in March, and described in an industry guidance document.

So on one level, Thursday’s FDA advisory panel will be about whether Genentech’s dataset looks solid enough to support an expanded approval for one breast cancer drug. But the vote, and the tenor of the debate among the FDA panel, could also have a more far-reaching influence on what the FDA considers acceptable medical evidence for cancer drug developers.

Those readers who make a living on knowing which way the wind blows at the FDA may want to tune in for the webcast of the panel meeting. The discussion is scheduled to start here at 8 am Eastern/5 am Pacific tomorrow.