OPINION
New approaches to
manage
CanCer
are deSPeraTely needed There were an eSTimaTed 12.7 million new CaSeS of CanCer worldwide in 2008 (wiTh 7.6 million deaThS). The inCidenCe of CanCer iS eXPeCTed To inCreaSe To 21 million new CaSeS By 2030. deSPiTe TremendouS SCienTifiC advanCeS in ThiS field, There remainS a large unmeT mediCal need for new CanCer drugS wiTh SuPerior effiCaCy, imProved SafeTy ProfileS and enhanCed ConvenienCe for The PaTienT. Cancer drugs generated global sales revenues of $48 billion in 2008, representing about six per cent of the pharmaceutical market. The cancer drug market is growing at almost twice the rate of the pharmaceutical market with a CAGR of 12 to 15 per cent. This large market opportunity has attracted intense competition. Some estimate more than 9,000 cancer drugs are under evaluation worldwide. In the U.S. alone, more than 900 cancer drugs are in clinical development. However, the majority of these investigational drugs are directed towards a small number (an estimated 16 or so) of molecular targets. A commonly held belief characterizes cancer clinical trials with a low success rate. Yet, the likelihood of a successful NDA for a cancer drug entering clinical development still exceeds six out of 12 pharmaceutical categories and is rapidly improving. Cancer drugs entering clinical testing from 1999 to 2004 had a success rate of nearly 20 per cent as recently reported by Dr. DiMasi and colleagues at the Tufts Center for the Study of Drug Development (Clin. Pharmacol. Ther. 94: 329-335, 2013). Interestingly, compounds studied solely in hematological indications had an even higher success rate, and unlike other fields, small molecules had a higher success rate than large molecules. 16 BIOTECHNOLOGY FOCUS November 2013
By: Robert Foldes
Several factors contribute to the traditionally low success rate of cancer clinical trials. First of all, cancer is not a single disease and it is extremely heterogeneous both in its origins as well as its manifestation. This usually translates to a heterogeneous patient population enrolled in clinical trials, including a large number of patients that are not predisposed to respond to the investigational therapy. The cancer phenotype is characterized by a large number of contributing pathways creating redundancies and compensatory mechanisms. Targeting one pathway may sometimes lead to only a temporary response. Recurrence of the disease can also be attributed to the presence of cancer stem cells. Secondly, patients enrolling in cancer clinical trials are usually no longer responding to one or more established treatment regimens. Mechanisms contributing to such drug resistance usually apply in a more general sense and are not drugspecific. Trials with such refractory patient populations usually lead to marginal results. And finally, approaches to address the above issues involve considerable stratification of patient populations to identify those most likely to respond to the investigational drug. This reduces the eligible patient population considerably, and together with the intense competition for those patients, makes enrollment challenging. Nevertheless, there is no question that stratification of patient populations to identify those most likely to respond to, and benefit from the investigational therapy is an important approach that is increasingly possible with the identification of suitable molecular markers. Thus, by applying this approach to a patient population that is not heavily pre-treated or with end-stage disease, it becomes more likely to increase the success rate. One strategy that has caught my attention, and is central to the focus of Viteava Pharmaceuticals, is referred to as “cancer interception.” I believe the Nobel laureate, Elizabeth Blackburn, coined this term to refer to delaying or avoiding the progression of cancer in early-stage patients (see Cancer Prev. Res. 4: 787792, 2011). Not to be confused with cancer CONTINUED ON PAGE 25
