Sanofi's Breast Cancer Bet

Sanofi's Breast Cancer Bet
Robert Langreth and Matthew Herper 05.31.09, 1:50 PM ET

ORLANDO, Fla. -- North Carolina resident Terri M. Allen noticed two strange pimple-like bumps on her scalp in June 2007. When she finally got them checked out, her worst fears were confirmed. Her breast cancer that had been removed in 2005 had returned with a vengeance, spreading to her sternum, hipbone and both lungs. Worse, she had a particularly nasty form called triple negative that doesn't respond to several standard treatments.

"I thought I was not going to make it," says Allen, now 54. Then her doctor told her about an experimental drug from Sanofi-Aventis that is looking promising in patients with her form of cancer. She started taking the drug along with chemo in March 2008. Within three months the tumors had virtually disappeared. "This is incredible to me," says Allen, who remains on the Sanofi drug and in remission. "I have no side effects and a completely normal standard of life."

Allen is among the first to benefit from a new class of drugs that aim at a weak spot in certain breast and ovarian cancers: limitations in their inability to repair DNA damage. While not cures, the drugs, called PARP inhibitors, may work well in triple negative breast cancers, about 15% of cases. They also show promise in patients with cancer due to inherited mutations in the BRCA1 and BRCA2 genes.

PARP inhibitors are among the few hot new drugs being highlighted at an otherwise sleepy meeting of the American Society of Clinical Oncology in Orlando. In a trial on 116 triple negative patients, patients who got the Sanofi parp drug lived 3.5 months longer than those who just got standard cell-killing chemotherapy regimens. "It is a big deal," says study leader Joyce O'Shaughnessy of the Baylor Charles A. Sammons Cancer Center. "We don't see survival advantages very often in [advanced] breast cancer." Adds Eric Winer, a breast cancer expert at the Dana-Farber Cancer Institute: "This is one of the most exciting results we have seen in a long time" for these patients. Triple negative cancers aren't responsive to standard hormone therapy or the drug Herceptin.

Sanofi-Aventis Chief Executive Christopher Viehbacher hopes that the drug will reinvigorate his company's cancer franchise. Sanofi sells some of the world's most used chemotherapy drugs, but has never made a name in the newer targeted drugs that are mainstays for Roche, Eli Lilly and Novartis. The PARP drug could help change this. Sanofi got the drug with its $500 million acquisition of BiPar Sciences, a biotech firm with only 18 employees that Sanofi bought earlier this year.

"This is a first-in-class drug, so it puts us back in the game of really innovative medicine," says Viehbacher. "There are other PARP inhibitors out there, but for the moment we've been able to stay in the lead." Parp stands for poly (ADP-ribose) polymerase.

Sanofi's biggest competition is AstraZeneca. It has tested its drug in an even narrower group of patients, women with inherited mutations in the BRCA1 or BRCA2 genes. (About 5% of breast cancer patients, including Allen, have one of these mutations.) Two small studies at the meeting found that the AstraZeneca's drug helped shrink 41% of breast cancer patients with the mutations and also helped ovarian cancer patients, without the need for chemotherapy.

One patient it helped is 70-year-old Los Angeles resident Barbara Shellow. She started on the AstraZeneca PARP inhibitor for her advanced ovarian cancer in July 2007, and her tumors quickly shrank. She has now gone 18 months without a relapse. "The drug has been a miracle for me," she says. Larger trials will be needed to confirm the benefits of both drugs before they can be approved.

If AstraZeneca or Sanofi had tested their drugs on all breast cancer patients, they likely would not have worked, as most breast tumors probably aren't being driven by aberrant DNA repair. "One of the key things is to match the cancer drug to the right patient population," says Alan Ashworth at the Institute of Cancer Research in London, who did an early experiment showing that patients with BRCA mutations might be susceptible to PARP blockers.

Many tumor types besides breast and ovarian may have DNA repair defects. A problem is there is no good test yet to determine which tumors have such defects. Researchers are furiously working to find one, says Ashworth.

"Getting at the molecular defects that are driving cancer is the only way to intelligently apply targeted therapy," says William Audeh, an oncologist at Cedars-Sinai Medical Center in Los Angeles who is testing the AstraZeneca drug. He says researchers need to start treating patients based on what mutations lie hidden inside their tumors, instead of based on what part of the body the tumor is in.