The 2008 Pipeline Report - Pharmaceutical Executive


The 2008 Pipeline Report

Pharmaceutical Executive


New agents for prostate, renal, and basal cell cancer

There are a record 750 oncology drugs in pharma's pipeline. Many won't make it to market—and even if they do, it will be easier than ever for some to get lost in the shuffle. Here are some cancer drugs we think will be impossible to ignore:

First off is Cougar Biotechnology's abiraterone (CB7630), a prostate cancer pill. Some studies have shown that prostate tumors grow by producing their own testosterone, and abiraterone attacks this mechanism by inhibiting CYP17A1, an enzyme involved in the production of testosterone. Fleur Pijpers, Datamonitor's oncology analyst. Pijpers forecasts that sales for this second-line hormone-refractory prostate therapy will reach $515 million by 2017, excluding whatever earnings Cougar gains from other therapies using the same molecule.

Axitinib (AG13736) is Pfizer's follow-on to Sutent (sunitinib), its receptor tyrosine kinase (RTK) inhibitor. The drug inhibits multiple targets, including VEGF-1, and is being tested for pancreatic, thyroid, and renal cancer. "This could be the next big thing," says Pijpers. "We have to wait for the Phase III results to come out, but for now it looks pretty decent—and with Pfizer's experience in renal cell carcinoma, it could do quite well." The drug targets slightly different kinases than Sutent—and has a slightly different MOA—which is why it might be a good follow-on to the earlier product, Pijpers says. It is regarded as a monotherapy, at least in renal cell carcinoma.

Another promising antiangiogenic is pazopanib, GSK's VEGF-2 inhibitor. Pazopanib also targets platelet-derived growth factor receptor (PDGFR) and c-kit. Like its cousin Avastin, the drug could also work for age-related macular degeneration.

"It's a promising drug," says Bruce Chabner, MD, clinical director at Massachusetts General Hospital in Boston. "It's active against lung cancer, sarcomas, and renal cell cancer."

Novartis' Afinitor (everolimus) is an MTOR inhibitor similar to Wyeth's sirolimus. Both have been launched as anti-rejection drugs after kidney transplants (Novartis' under the brand name Certican, Wyeth's as Rapamune). Afinitor is in trials for a number of cancers and is awaiting approval for advanced kidney cancer. (At press time, the company announced that FDA had requested additional data on the drug and that approval would be delayed by several months.)

Elesclomol is an injectable apoptosis stimulator aimed at melanoma, which is one of the tumor types for which the fewest treatment options exist. Old systemic chemotherapies are still used for metastatic patients, although they are generally thought to be ineffective, and off-label prescriptions are in use as well, according to Pijper.

"Drug developers are interested in tumor types like melanoma," says Pijper about the Synta/GSK project, "Even though their incidence is not as high as the big four tumor types: breast, prostate, colorectal, and lung cancer. The unmet needs of melanoma are so great that if a drug gets approved, it has a good chance of being commercially successful."

Ramcirumab is a fully human monoclonal antibody that could have fewer side-effects than Avastin, a humanized monoclonal antibody. Lilly scooped up ImClone in part due to this drug—but expect an uphill battle for the developer. The Phase III trial won't end until 2012. By that time, Avastin may so dominate the market that it could prove impossible for ramcirumab to gain a toehold. "But if the drug shows simply amazing results," Pijpers says, "It might do all right."

Further back in the pipeline, GDC-0449 by Curis and Genentech is creating a stir with its new MOA against basal cell cancers. The drug interferes with the so-called hedgehog pathway, which has a mutation in the basal cell and colorectal cancers. The drug has a long way to go, "but it was very very active against basal cell cancers and that is important," Chabner says.

Finally, one of the most talked about classes of new cancer drugs—PI3-k inhibitors—has made it to the clinic. "There is a mountain of evidence that implicates the PI3-K pathway in everything bad in cancer from A to Z: growing, metastasizing, invading, causing growth of blood vessels, resisting cell death," said Chabner. It's too early to say much about them as treatments, but watch for these therapeutics in future Pipeline Reports.


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