Cancer: Treating Patients Instead of Disease
Highly targeted therapies have made a comeback in cancer, with the approvals of Pfizer's Xalkori (crizotinib) and Roche/Daiichi-Sankyo's
Zelboraf (vemurafenib) this year—both of which employ companion diagnostics, which dramatically improve patient outcomes.
"In an era where more and more cancer drugs are failing because they don't demonstrate efficacy in the overall population,
these 'magic bullets'—drugs that target specific genetic profiles—are going to revolutionize the market, at least for their
niche target populations," says Kiran Meekings,a consultant at Thomson Reuters Life Sciences Consulting "We need to stop thinking
about cancer as one, or several, diseases and instead we need to think about it as a set of distinct independent populations,
each of which need a targeted set of treatments."
In pancreatic cancer, Clovis Oncology, a startup biopharma in Boulder, Colo., has fingers crossed over its CO-101 compound,
a first-line treatment for metastatic pancreatic cancer. Clovis raised $130 million in its November IPO, and Roche is developing
a companion diagnostic for CO-101 through its Ventana Medical Systems. This biomarker-driven clinical strategy could help
Clovis succeed where others fail, given that C0-101 is a lipid-conjugated derivative of Gemzar (gemcitabine), Lilly's long-time
treatment for the disease. Gemzar's efficacy as a single agent is moderate at best, however, with a median overall survival
of just under six months; the drug is often coupled with other chemotherapy agents. Clovis estimates that "two-thirds of pancreatic
cancer patients have limited cellular uptake of [Gemzar], due to deficient expression of hENT1—the transporter protein thought
to facilitate cellular entry for Gemzar." CO-101's companion diagnostic would identify patients with low levels of hENT1 expression,
which have been shown to correlate with poor Gemzar outcomes.
The multifactorial abnormalities in cancer—which means multiple targets—continues to present a problem, but several cancer
drugs coming down the pipeline could do more than add a few months of progression-free survival. In hematology, Phase II data
on Celgene's pomalidomide, an oral treatment for Revlimid and Velcade refractory patients with multiple myeloma, will be hyped
during the American Society of Hematology meeting early this month. Onyx's carfilzomib, also for multiple myeloma, is the
"most exciting thing to happen in multiple myeloma in maybe a decade," according to Selvaraju. Carfilzomib was fast-tracked
by FDA in January for patients with relapsed or refractory multiple myeloma, and Onyx launched an expanded access program
with the Multiple Myeloma Research Foundation in August, making the drug available to eligible patients across 40 medical
centers in the US.
Medivation/Astellas' MDV-3100, discovered at UCLA, is an oral therapy being tested for prostate cancer; the drug received
fast-track designation in November, after the company's AFFIRM trial data showed an almost five-month increase in median overall
survival. If approved, MDV-3100 would compete with J&J's Zytiga, which has made inroads against Dendreon's Provenge vaccine;
Provenge was expected to hit blockbuster sales figures, but hasn't performed as well as expected. However, CMS issued a National
Coverage Decision last July, requiring Medicare contractors to cover the use of Provenge for treatment of asymptomatic or
minimally symptomatic hormone refractory prostate cancer, which could standardize coverage and lift sales by the end of this