Sunday, May 31, 2009

More on BSI-201 PARP Inhibitor

From Bloomberg News

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.
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.


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.


The cancer in the study is called
triple negative breast cancer because it lacks the three genetic targets needed
for the most effective medicines. 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

“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.”

Link to article

ASCO Conference This Week

News about results of a study on PARP inhibitors and triple negative breast cancer. This study compared Gemzar and Carboplatin with and without BSI-201 in women with triple-negative metastatic breast cancer as either the first chemo for metastatic disease, or after one or two prior chemo regimens. BiPar announded interim safety data from this trial at the San Antonio Breast Cancer Symposium, finding NO additional signigicant toxicity attributed to the experimental drug.

Quick note from Musa Mayer who is attending the Conference:

While the full presentation won't occur until tomorrow afternoon, today they released some of the findings, and I just had to tell you what I know, so far:

"Analyzes of the first 86 patients of a planned 120 patients showed that BSI-201 + G/C (Gemzar and Carboplatin) had improved CBR (clinical benefit rate, those with tumor shrinkage or stable disease), median PFS (progression-free survival) and median OS (overall survival), compared with G/C alone. The frequency and nature of adverse events (AEs) did not differ between arms."

How much of an improvement is what's impressive.

* CBR is 12% with G/C vs. 52% with G/C+BSI-201.

* Median PFS is 87 days with G/C and 211 days with G/C+BSI-201 with a HR (hazard ratio) of 0.30. In case these numbers don't mean anything to you, this amounts a 70% improvement in progression-free survival.

* Median OS: patients in the G/C arm had a median survival of 169 days, but patients on the G/C arm of the study had a median survival of more than 254 days, for a HR of 0.24. That means that patients exposed to the experimental drug lived 76% longer.

If these findings hold up in the completed study and in a full-scale Phase III trial of sufficient size to be definitive--and that's a big if, of course--this magnitude of benefit will be beyond any breast cancer drug we've seen in the 15+ years I've been following drug development. However, this is a small number of patients, not even the full number enrolled in the study, and the study itself isn't sufficiently powered to show a definitive difference.

The results of the entire study, with all 120 patients along with some studies of PARP expression will be presented tomorrow afternoon--you'll be hearing about it on the news. I'm excited!

Great news, Musa! Thanks for sharing.