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
Carfilzomib was supposed to be filed with the FDA in late 2010, but the submission was delayed after Onyx scaled up its manufacturing
process in anticipation of approval and launch. The clinical profile of the drug didn't change, but FDA's Chemistry, Manufacturing
and Controls (CMC) division requested additional information about its manufacturing capabilities involving "minor variations,"
primarily related to "equipment temperature variances," according to a company statement. Not surprisingly, Coles puts a positive
spin on the delay. "As it turned out, [delaying an NDA filing] was a wise decision. What we really want is a high-quality
NDA ... and we've done several things to strengthen our case. We filed for and received fast-track designation in January,
and that's very good because it does two things: It allows us to submit the NDA on a rolling basis, and as a result, we've
submitted the first of three modules, which is the non-clinical piece covering animal studies and toxicology," says Coles.
"The second piece is the clinical module, and the third is the CMC module." Fast-track rolling submissions "help to reassure
investors that we are on track for filing the NDA as early as the middle of this year." Last month, Ted Love, EVP and head
of research and development and technical operations at Onyx, said the NDA would be submitted in the "July to August" time
frame. The company is betting on accelerated approval, and plans to launch first in the US without the aid of a partnership.
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.