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OPINION
New approaches to manage CanCer
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are deSPeraTely needed
By: Robert Foldes
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 fi elds, small molecules had a higher success rate than large molecules.
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 drugspecifi c. Trials with such refractory patient populations usually lead to marginal results. And fi nally, approaches to address the above issues involve considerable stratifi cation 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 stratifi cation of patient populations to identify those most likely to respond to, and benefi t from the investigational therapy is an important approach that is increasingly possible with the identifi cation 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
Canada and eu ComPrehenSive eConomiC and Trade agreemenT (CeTa) reaChed in PrinCiPle:
What is the impact on pharmaceutical patents?
On October 18, 2013, after more than four years of negotiations, Canada and the European Union reached, in principle, a free trade agreement, the Comprehensive Economic and Trade Agreement (CETA). By reaching this agreement, Canada agrees to two important demands of the European Union concerning the intellectual property rights of Canadian innovative pharmaceutical companies, in order to bring its intellectual property system in line with other Western countries. These demands were (1) the adoption of a patent term restoration for pharmaceutical patents and (2) an effective right of appeal under the Patented Medicines (Notice of Compliance) Regulations.
1. Patent Term Restoration
Although the text of the agreement has not yet been released, it is understood that Canada will implement an up to two-year patent term restoration in order to compensate for the administrative procedures (particularly related to the approval of new drug submissions) that take place between the filing of a patent application for a drug and the issuance of the first notice of compliance. This two-year patent term restoration may also have the effect of delaying the entry of generic competition.
It is also understood that Canada will provide innovative brand companies with an effective right of appeal under the Patented Medicines (Notice of Compliance) Regulations. This will require amendments to the Regulations and will reverse the jurisprudential trend in Canada to the effect that, when the prohibition application of the innovator is dismissed and the notice of compliance of the generic is subsequently issued as a result, any appeal by the innovator becomes automatically moot unless the Court exercises its discretion to nevertheless hear the appeal. (Pfizer Canada Inc. v. Apotex Inc. (2001), 11 C.P.R. (4th) 245, para. 21 (C.A.F.) (application for leave to appeal dismissed with costs, S.C.C. [2001] S.C.C.A. no. 111); Apotex Inc. v. Merck Frosst Canada Inc., [1999] J.C.F. 55, paras. 4-6 (C.A.F.).
Finally, it is expected that the future amendments will address duplicative patent litigation sometimes generated by the Regulations.
Members of the innovative pharmaceutical industry have welcomed the new agreement although some would also have hoped for an extended data protection period, increasing the current eight-year period of protection to a 10+1-year period of protection as currently provided by European countries.
No full text of the agreement has been released yet. The ratification is expected to take 18 to 24 months.
Mélanie Bourassa Forcier and Julie Desrosiers are members of the Fasken Martineau LLP Montréal office Life Sciences Group.
Republished with permission ofthe Fasken Martineau LLP Montréal office Life Sciences Group
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