Box 1. Blockbuster researchers

At what point in a drug's development history does its blockbuster potential become obvious? That first eureka moment came for JoAnn Suzich, senior director of infectious disease research at MedImmune, when she saw the initial animal data on an oral canine papilloma virus vaccine. The science related to her work would later be licensed by both Merck and London's GlaxoSmith-Kline (GSK) as the basis for their HPV vaccines: Gardasil, which is already marketed, and GSK's Cervarix, which is in phase 3 trials.

The animal results were so good—providing almost full protection—that "when the data came back it seemed too good to be true, but it was repeatable," she said. Once other researchers started reporting similar results for other animal models, like rabbits and cows, Suzich knew she and her team were really onto something.

But it wasn't until Merck and GSK each conducted large-scale feasibility studies in women, "that everybody became believers," says Suzich. "Merck reported 100% protection."

Once MedImmune realized the scope a phase 3 clinical trial would require, with 15,000 to 30,000 women on an international scale, the company knew that it couldn't handle the R&D on its own. "MedImmune at the time wasn't capable of doing that," Suzich remarks.

MedImmune carried the clinical trials through phase 1 and phase 2, with Suzich's responsibility ending after that point.

For Napoleone Ferrara, a Genentech scientist who was also working in an uncharted field, angiogenesis and anti-VEGF, the breakthrough moment for Avastin came far later, when the company got phase 3 results in colorectal cancer. "The data were very surprising," Ferrara remembers. Avastin had a "very, very significant effect on progression-free survival."

Previously, scientific dogma had been that angiogenesis could not be a viable approach to cancer treatment. In fact, Avastin research, which had initially started in second-line, metastatic cancer had shown disappointing results. "That would be enough to discourage a lot of people," he notes.

But the "most difficult part," adds Ferrara, "was going into uncharted territory. There was nothing really known about angiogenesis."

Luckily for Ferrara and Genentech, the company had encouraged him to pursue the work on angiogenesis and anti-VEGF that had initially started out as just a diversion from his research on the role of relaxin in the human reproductive process.

New indications continue to be rolled out for Avastin; Ferrara believes the most intriguing of these is its use in early-stage cancer, where he says the treatment shows even stronger efficacy.