Biotech Values

[DewDiligence]

BSI-201 is the drug SNY recently acquired in the buyout of BiPar Sciences.

http://www.bloomberg.com/apps/news?pid=20601087&sid=a9X3jOZqvDgs

›Drugs Kill Cancer by Halting Tumor’s Ability to Heal Itself

By Tom Randall
May 31, 2009 08:30 EDT

May 31 (Bloomberg) -- An experimental cancer drug made by Sanofi-Aventis SA helped patients with advanced breast tumors live more than 60 percent longer using a new method that stops diseased cells from healing themselves, a new study found.

The treatment, called BSI-201, shrank tumors and slowed new growth in a study of 116 patients with so-called triple- negative breast cancer, an aggressive disease that doesn’t respond to many treatments. Results were presented today at the American Society of Clinical Oncology in Orlando, Florida.

BSI-201 leads an emerging class of treatments known as PARP inhibitors. Most cancer treatments work by blasting DNA with chemotherapy or radiation. Cancer can fight back by using PARP enzymes to fix damaged strands of DNA. The new medicines are designed to block the enzymes and kill the cancer.

“These PARP inhibitors are the biggest story in breast cancer, by far, and it’s going to be a huge bombshell” at the cancer conference, said Powel Brown, director of cancer prevention at the Lester and Sue Smith Breast Center at Baylor College of Medicine in Houston, Texas, in an interview before the meeting. “This mechanism is so hugely positive that this will be FDA approved within probably a year or two.”

There were no significant side effects from the BSI-201 treatment, which was added to standard chemotherapy in the research. A separate study presented at the conference showed a similar drug, called olaparib and made by London-based AstraZeneca Plc, shrank tumors even when administered without chemotherapy or radiotherapy.

Other Cancers

The tests, the second of three stages typically required for regulatory approval, focused on breast cancer. However, the PARP inhibitor method of blocking DNA repair may also work against other cancers and might reduce the amount of chemotherapy needed to treat a variety of patients, said Paul Chew, chief medical officer for Paris-based Sanofi, in an interview at the conference yesterday.

“It’s a portal to other tumors,” said Chew, who was appointed to his job in March. “This opens up a new era of cancer treatment.”

A month after Chew’s appointment, Sanofi agreed to purchase BiPar Sciences Inc. to gain BSI-201. The company will pay as much as $500 million, based on the success of the drug [#msg-37045585].

Sanofi will begin enrolling 400 patients in the next two months for an expanded trial to confirm the results. That could take as little as a year to complete before submitting to regulators for marketing approval, Chew said.

The drugmaker believes the new trial “will be sufficient” for approval, he said.

Fixing DNA

Healthy human cells have six different mechanisms to repair DNA. As cancer develops, many of those mechanisms break down, leaving the cell reliant on PARP to fix genetic damage from cancer treatments. Researchers have found that severe forms of cancer in the ovaries, uterus, lungs and pancreas all have unusually high PARP enzyme activity, meaning they could make good targets for the new therapies, according to Barry Sherman, BiPar’s chief medical officer.

In Sanofi’s study, half of patients were given BSI-201 and a combination of chemotherapies, carboplatin and Eli Lilly & Co.’s Gemzar, and half were given chemo and a placebo. About 60 percent of patients who took BSI-201 saw their tumors shrink and cancer slow, almost three times as many as those who took only chemotherapy. The median lifespan after treatment with BSI-201 was 9.2 months, compared with 5.7 months in the control group.

15 Percent of Breast Cancer

The cancer in the study is called triple negative breast cancer because it lacks the three genetic targets needed for the most effective medicines [“triple negative” means estrogen-negative, progesterone-negative, and HER2-negative]. It is responsible for about 15 percent of all breast cancers and sickens younger women more than other forms. If the cancer is detected early enough, treatment with a PARP inhibitor may be able to permanently destroy the tumors, Sherman said in an interview at the conference yesterday.

“There is an opportunity here to actually use the term ‘cure’ when it’s applied to early-stage disease,” Sherman said. “That is perhaps one of the most exciting notions to come out of this. This is the forefront of a field that is about to open up, about DNA repair.”

Abbott Laboratories and Pfizer Inc. are also investigating PARP inhibitors in early-stage human trials. Abbott’s version, called ABT-888, is being examined in 10 clinical trials to determine which treatments it works best with, said Vincent Giranda, director of PARP research at Abbott Park, Illinois- based company.

Other Disease Hints

There are “hints” that PARP inhibitors may show benefits in diseases other than cancer and may one day be used to limit damage after a heart attack or stroke, Giranda said. For now, companies are focusing on oncology, where the most dramatic results may come, he said in an interview last week.

The AstraZeneca trial focused on breast cancer patients with a mutation in a gene called BRCA, another severe disease form affecting about 5 percent of breast cancer patients. The mutation hampers other mechanisms to repair DNA, making the cancer especially reliant on PARP enzymes. The trial of 54 patients showed olaparib was safe and shrank tumors. It wasn’t designed to measure the drug’s ability to slow the disease.

“These two studies, taken together, show that PARP is a very promising drug target,” said Richard Schilsky, president of ASCO and associate dean for clinical research at University of Chicago, in an interview before the meeting. “You’re going to hear a lot more about PARP inhibitors as time goes by.”

‘Biggest Story’

Breast cancer is the second most common malignancy in women, after skin tumors, according to the Atlanta-based U.S. Centers for Disease Control and Prevention. About 187,000 women were diagnosed with breast cancer and 41,000 women died from it in 2005, the most recent year for which CDC data are available.

“The biggest story in breast cancer right now is the PARP inhibitors,” said Clifford Hudis, chief of breast cancer medicine at Memorial Sloan Kettering Cancer Center in New York, in a telephone interview last week. “Any time you open up a new target, that’s an exciting moment. These drugs may potentially be active not just to treat metastatic disease but to prevent recurrence.”‹