Repairing the U.S. Cancer Care Delivery System: Should It Include a New Exclusivity Incentive?

By Kurt R. Karst –      

We’ve previously noted the resurgence of interest in (and controversy over) brand-side exclusivity.  There’s the QI Program Supplemental Funding Act of 2008 (Pub. L. No. 110-379), which gave new life to “old” antibiotics.  FDC Act § 505(u), titled “Certain Drugs Containing Single Enantiomers,” and created by the 2007 FDA Amendments Act (see summary here), permits sponsors of enantiomers to elect to claim “new active ingredient” status and be awarded 5-year NCE exclusivity when new indications are developed for the enantiomers (see our previous post here).  The Generating Antibiotic Incentives Now Act (“GAIN Act”), passed as part of the 2012 FDA Safety and Innovation Act (see summary here) amended the FDC Act to add Section 505E to, among other things, grant an additional 5 years of marketing exclusivity upon the approval of an NDA for a drug product designated by FDA as a Qualified Infectious Disease Product. 

Myriad proposals for new or add-on exclusivities (or abolishment of exclusivity) have also cropped up in Congress in recent years.  For example, there’s the Combination Drug Development Incentive Act of 2013 (H.R. 2985), which would amend the FDC Act to allow for a grant of NCE exclusivity for a new combination of drugs even if both were previously approved separately (see our previous post here). There’s also the Life-Threatening Diseases Compassion through Combination Therapy Act of 2012 (H.R. 6502) (modeled after the GAIN Act) that would amend the FDC Act to add 6 months of marketing exclusivity to 5-year NCE exclusivity, 3-year new clinical investigation exclusivity, or 7-year orphan drug exclusivity for a drug product approved under an NDA and that contains a “significant drug combination” designated as such by FDA (see our previous post here).  

These types of exclusivity incentives, realized after a product has been developed, have been described as “pull” incentives, and are different than so-called “push” incentives, which focus on removing barriers to product development (e.g., tax credits and grants) (see our previous post here).  A recent report from the Institute of Medicine (“IOM”), titled “Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis,” recommends the creation of a new “pull” incentive to achieve the goal of expanding the “breadth of data collected on cancer interventions for older adults and individuals with multiple comorbid conditions.”  According to the report, “Congress should amend patent law to provide patent extensions of up to six months for companies that conduct clinical trials of new cancer treatments in older adults or patients with multiple comorbidities.”  The recommended exclusivity incentive is part of a broader conceptual framework for improving the quality of cancer care that includes various components, such as engaged patients, an adequately staffed, trained and coordinated workforce, evidence-based care, learning health care information technology, translation of evidence into clinical practice, quality measurement and performance improvement, and accessible and affordable care.

The new exclusivity incentive recommended in the IOM report is inspired by the pediatric exclusivity incentive added to the statute (at FDC Act § 505A) by Section 111 of the 1997 FDA Modernization Act, and now known as the Best Pharmaceuticals for Children Act (“BPCA”).  Citing a 2012 IOM report on the BPCA (and its sister law, the Pediatric Research Equity Act) (see more here), the 2013 IOM report states:

A recent IOM committee concluded that studies conducted under the pediatric patent exclusivity laws “are yielding important information to guide clinical care for children” (IOM, 2012c, p. 26). . . .  In addition, the pediatric patent exclusivity has contributed to researchers conducting more than 300 pediatric studies between 1997 and 2002 (Li et al., 2007; Milne, 2002).  These studies have led to revised labeling of dosing, safety, efficacy, new pediatric formulations, and extended age limits for many of the studied drugs (Li et al., 2007; Rodriguez et al., 2008).  It is probable that patent exclusivity in cancer would lead to a similar increase in research conducted in older adults and individuals with multiple comorbidities, and to an increase in knowledge about how to treat this population.  Thus, the committee recommends that Congress amend patent law to provide patent extensions of up to six months for companies that conduct clinical trials of new cancer treatments in older adults or patients with multiple comorbidities (Recommendation 5).

The IOM report goes on to note, however, that ther are some concerns with and criticisms of the BPCA:

The committee is concerned about some of the known limitations of the patent extension program in pediatrics, but believes the need for more data on older adults with cancer and individuals with multiple comorbidities is so great that it justifies modeling this program in drugs used to treat older adults with cancer and individuals with multiple comorbidities. . . .  FDA registration trials are conducted for the narrow goal of bringing new treatments to the market.  Alternative strategies that mandate the inclusion of older adults and patients with multiple comorbidities in FDA registration trials have serious limitations.  Such a mandate could make it more challenging to determine the efficacy and safety of a new treatment.  This could make drug development more expensive, potentially require larger trials, and delay or prevent new drugs from entering the market.

. . . .  A recent review of the pediatric exclusivity provision noted that it is difficult to measure any improvements in children’s health care that have resulted from the program (Kesselheim, 2011).  The research conducted for the purpose of achieving a pediatric extension often has serious methodological limitations, including the only rare inclusion of drugs most frequently used by children.  Most of the studies are conducted in populations of older pediatric patients (not children under the age of 6 or 2), and often at sites outside of the United States (Boots et al., 2007; Grieve et al., 2005; Pasquali et al., 2010).  The results of the research are often unpublished, and thus, not subject to peer review (Benjamin et al., 2009).  When the research is published, it often focuses on findings substantively different from those highlighted in the FDA reviews and labeling changes (Benjamin et al., 2008; 2009).  Additionally, society has borne substantial costs from the delayed entry of less expensive generic versions of a drug onto the market. . . .  The high cost of patent extension is of particular concern when the higher drug prices are passed on to patients, because this could lead to reduced medication adherence during the extra six months of elevated prices (Kesselheim, 2011).  Due to the high price tag, the program has been criticized for overcompensating manufacturers (Kesselheim, 2011). The median cost of conducting clinical trials under this program was more than $12 million between 2002 and 2004, and the median net economic benefit to manufacturers was more than $134 million (Li et al., 2007). Another study found the ratio of net economic return to cost was 17 to 1 (Baker-Smith et al., 2008). 

Despite these perceived limitations with the BPCA, however, the IOM report says that they “may be preventable in a geriatric oncology exclusivity program by having stringent requirements on the types of clinical trials that qualify for market exclusivity.”

This is not the first time a BPCA-like exclusivity proposal has been suggested as a mechanism to incentivize drug development.  In June 1998, the Alliance for Aging Research published a report, titled “When Medicine Hurts Instead of Helps: Preventing Medication Problems in Older Persons,” recommending the creation of an exclusivity provision for companies that study their products in the elderly.  In addition, in 2005, Congress considered (but ultimately rejected) a proposal to create so-called “wildcard” exclusivity as part of the Biodefense and Pandemic Vaccine and Drug Development Act (see here and here) to spur the development of medical countermeasures for terrorist attacks involving chemical, biological, radiological, or nuclear agents. 

Whether the new IOM report will result in Congress putting pen to paper to propose yet another new exclusivity regime remains to be seen.  As the government shutdown enters its third week, Members of Congress have other concerns on their minds.