Antibodies in the Headlines
June 2011 saw the formation of a partnership that employs a strategy now being used by some pharma companies to facilitiate development of their individual targeted drugs. BMS and Roche said they would conduct a Phase I/II study to evaluate the combination of BMS’ approved melanoma drug, Yervoy, and Roche’s marketed melanoma therapy, Zelboraf, in patients with a specific type of late-stage melanoma.
Yervoy is a recombinant mAb that blocks CTLA-4, and Zelboraf is an orally administered BRAF inhibitor. FDA approved Yervoy in March 2011 for unresectable or metastatic melanoma and Zelboraf last August for late-stage or unresectable BRAF V600E melanoma. The combo will be tested in patients with tumors expressing a mutant form of the BRAF oncogene (V600E). The hope is that the combination will increase the duration of response and improve the immune response attack.
In forming their collaboration, BMS and Roche are responding to a trend among oncologists who favor the use of combinations of new therapeutics to treat cancer. This May BioTrends Research Group released findings from the second wave of its LaunchTrends® Yervoy and Zelboraf report, in which 103 U.S.-based medical oncologists were surveyed about their treatment patterns in advanced melanoma.
The surveyed medical oncologists noted positive patient treatment experiences with these agents and plans to utilize them more often when treating advanced melanoma. In terms of interest in late-stage candidates for advanced melanoma, doctors were most interested in Yervoy in combination with another agent such as Zelboraf, Merck & Co.’s Temodar, or generic dacarbazine.
Another targeted anti-cancer mAb therapeutic that has been on the market for a while received a blow in June 2011. The Onoclogy Drug Advisory Committee (ODAC) sided with FDA staff officials, who had concluded that Avastin does not prolong overall survival in metastatic breast cancer patients or offer a benefit in slowing the progression of the disease that outweighs the drug’s risks. In three 6–0 votes, the panel recommended reversal of the FDA’s approval of the $7.7 billion drug in combination with paclitaxel for Her2-negative breast cancer patients who have not been treated with chemotherapy. Avastin remains on the U.S. market as an approved treatment for certain types of colon, lung, kidney, and brain cancers.
Coincident with the ODAC decision, the EC broadened the existing breast cancer label for Avastin to include its use in combination with Xeloda as first-line therapy against metastatic disease.
Avastin may stage a comeback, though, as findings reported in the January issue of The New England Journal of Medicine suggest the antibody might be useful in patients in which the cancer has not spread. The study was supported by grants from Roche, Genentech, Eli Lilly, NCI, HHS, and the Public Health Service.
In one of two studies, a little over 33% of women given Avastin plus chemotherapy for a few months prior to surgery had no sign of cancer in their breasts at surgery compared to 28% of women given chemotherapy alone. In the other study, over 18% of patients treated with Avastin with chemotherapy had no cancer in their breasts or lymph nodes at surgery, compared to 15% of those on chemo alone. Both studies noted, however, that use of the antibody added to the toxicity of an already difficult treatment regimen.