Renewed Focus

Andrew is doing fine now, but the experience left a mark on his father. After a three-year stint at Vertex, Coles resigned in 2005 and took a job as CEO at NPS Pharma, before joining Onyx, a company focused almost exclusively on developing cancer treatments, in 2008.

On the divide between Big Pharma and biotech, Coles says Big Pharma companies "are superb at marketing and distribution and commercialization." In contrast, the biotech industry has "become expert at discovering new compounds, both large molecules and small molecules." Combining a biotech with a large pharma "would almost make a perfect company, because you'd get the innovation of one with the scale and the distribution capability of the other," says Coles. "But the two really have grown up quite differently. Nevertheless, I think biotech is now beginning to emerge as a commercial powerhouse within the industry as well."

Carfilzomib's success depends on a couple of factors, including how soon it gets to market, and "how far ahead it comes to the market relative to generic Velcade, which is the lead product in the class," says Liang. "It also may hinge, to some extent, on how widely the newer forms of Velcade are adopted. One of the differentiating factors for carfilzomib is low side effects and low neuropathy, and that can be reduced for [Millennium/Takeda's] Velcade, by dosing it less frequently, so instead of twice a week, there has been a weekly Velcade dosage that has shown reduced neuropathy." Even so, Liang says carfilzomib "probably still offers a preferable [risk] profile," with very low incidences of neuropathy.

Overall, analyst Liang is a bit less optimistic than Coles as to the ultimate outcome: "Whether carfilzomib gets accelerated approval is still questionable," he says.

In addition to carfilzomib's beneficial risk profile, Coles says standard therapies "only succeed in this very sick [multiple myeloma] population about 10 percent to 11 percent of the time. We believe that the clinical data from the study we're filing on [Phase IIb 003-A1], which showed that we more than doubled that overall response rate, from 11 percent to 24 percent, is very strong. Also, the overall survival in this particular study was 15.6 months, compared to six to nine months with the currently available therapies." Those data refer to patients that have relapsed and are refractory to most new therapies.

Last December at the American Society of Hematology meeting in Orlando, Fla., Onyx announced data on carfilzomib from a study done with newly diagnosed patients that had never been treated with any drug. The study, conducted by the University of Michigan's Comprehensive Cancer Center, found that patients given carfilzomib in combination with Celgene's Revlimid (lenalidomide) and a steroid called dexamethisone, had an overall response rate of 100 percent after four cycles of therapy, says Coles. Of that 100 percent response after four cycles, 36 percent of the patients had a complete response, meaning no disease detected. After eight cycles, 67 percent of the patients had a complete response.

Onyx's Phase III ASPIRE trial, initiated a year ago, is also testing the same triple combo—carfilzomib, Revlimid, and low-dose dexamethisone—in patients with relapsed multiple myeloma. Another Phase III trial, FOCUS, is testing carfilzomib as a single agent in treatment-refractory patients with relapsed disease. "We think that cancer in general is a tough disease to cure, but in a uniformly fatal disease like multiple myeloma if we can give patients hope that, like with diabetes or hypertension, their lives can be extended and myeloma can become a chronic disease, we will have made an important contribution to the field of medicine," says Coles.