Genentech Eagerly Awaits FDA Word on 2nd Breast Cancer Drug

Xconomy San Francisco — 

Genentech came out with the first targeted antibody drug for breast cancer almost 15 years ago, and made headlines this week with a “supercharged” version that beats the original. What fewer people may realize is that it’s also gearing up this week to start selling a new and different targeted drug for breast cancer.

The South San Francisco-based company, a unit of Roche, is eagerly awaiting word from the FDA on whether it has the green light to market pertuzumab (Perjeta) in the U.S. as a new therapy for women with breast cancer that overexpresses the HER2 protein. The drug, pronounced per-JETT-uh, is designed to be given in combination with the original trastuzumab (Herceptin) for women who are getting their first round of treatment for metastatic disease, or for those who have suffered a relapse after surgery. The FDA gave this drug’s application a faster-than-usual six-month regulatory review, which it sometimes grants to groundbreaking new therapies. The agency’s deadline to complete its review is Friday.

Getting to the cusp of FDA approval represents a comeback for this drug, which could easily have been tossed on the R&D scrap heap a few years ago. The program stalled in 2005 when Genentech said the drug showed “limited activity” as a single-agent in mid-stage clinical studies against ovarian, breast, and prostate tumors. But the company’s scientists argued that it was worth trying pertuzumab in combination with trastuzumab to see if two targeted therapies for breast cancer might be better than one.

It was a provocative question that Genentech had to spend a lot of time and money to answer. The basic idea is this: The original trastuzumab zeroes in on a target known as HER2 that is abundant on the surface of breast cancer cells in about one-fourth of patients with a gene mutation. It has proven to be effective since winning FDA approval in 1998, but it’s not a cure, and patients eventually develop resistance.

By creating a different Y-shaped antibody that binds to a different location on the HER2 molecule, Genentech hoped to achieve a more comprehensive blockade of members of the HER family of signaling molecules, which are thought to help tumors spread and grow. The bet was essentially that the two drugs together could help hold the cancer in check for a greater percentage of patients, without adding excessive side effects.

Genentech ran 17 clinical studies of pertuzumab, giving the experimental medicine to 1,412 people, Willson says. The most important of those studies was called Cleopatra. That trial enrolled 808 patients who were getting their first round of therapy for breast cancer that overexpresses the HER2 protein, and which had spread through the body. Researchers said patients on the new regimen of pertuzumab, trastuzumab and chemotherapy were able to keep their tumors from spreading for a median time of 18.5 months, compared with 12.4 months for those on the standard trastuzumab and chemo alone.

Researchers haven’t yet been able to gather enough data on whether the new drug combo can help patients live longer, although that data should be available in 2013, Genentech spokeswoman Susan Willson says.

Any time researchers create new drug combinations, they worry about drug toxicity, but that didn’t appear to be a problem in the Cleopatra study. The second antibody didn’t appear to add any toxicity to the heart, and researchers saw very little difference in side effects when the new drug was added, other than a few more cases of white-blood cell depletion, according to findings published in the New England Journal of Medicine. 

“This is huge. It is very uncommon to have a clinical trial show this level of improvement,” in slowing the spread of tumors, said Jose Baselga, the chief of hematology/oncology at Massachusetts General Hospital, in a statement about the Cleopatra study last December.

Dietmar Berger, Genentech’s vice president of clinical hematology/oncology, said last week that by developing trastuzumab, pertuzumab, and the “smart bomb” T-DM1, “this really shows how as a company we are committed to the HER2 target and the HER2 family, and how much we are committed to improve the benefit for patients.”

If the FDA approves the second antibody, cost will be one of the first and most important questions Genentech will have to answer. Herceptin already costs $4,500 a month (which translates to $54,000 a year), meaning that co-pays are expensive for patients with health insurance. Adding another antibody drug to the mix, if priced similarly, will add a significant new cost for insurers or patients. Genentech isn’t commenting yet on the price of the new drug, although it will if the product wins FDA approval, says Willson, the company spokeswoman.

The price of the drug, combined with the large numbers of patients it can be prescribed for, adds up to big business. About 229,000 women in the U.S. are diagnosed with breast cancer each year, and about one-fourth of patients have tumors that overexpress the HER2 protein. Trastuzumab is one of the world’s best-selling drugs, generating $6.8 billion in worldwide sales in 2010, according to Reuters. The new antibody, pertuzumab, is expected to add $274 million in annual sales by 2015, according to the average estimate of analysts polled by Thomson Reuters.