21st Century Cures: Waking Up Dormant Drug Therapies

A similar version of this Health Alert appeared at Forbes.

Representative Fred Upton, Chairman of the House Energy & Commerce Committee, recently released a discussion draft of legislative language for the 21st Century Cures Initiative. This initiative attempts nothing less than to “boil the ocean” of regulations and incentives that govern medical innovation in the U.S. The 400-plus-page draft rolls up a number of previously proposed bills (including an updated version of Representative Marsha Blackburn’s SOFTWARE Act, discussed in a previous Health Alert).

A large share of the draft incorporates legislation designed to improve the incentives for inventing new medicines, or finding new uses for old medicines. This is important, because we are facing a crisis in pharmaceutical innovation.

One of these is the Dormant Therapies Act, put forward by Senator Orrin Hatch (R-UT) and Senator Michael Bennet (D-CO). This would give a “dormant therapy” 15 years of marketing exclusivity after approval by the Food and Drug Administration (FDA), significantly more than currently exists.

The designation of “dormant therapy” will add to the complexity of other designations already in law: breakthrough, pediatric, orphan and fast-track. Currently, the longest terms of exclusivity are for orphan drugs (seven years) and biologics (12 years). Most new drugs only receive five years of marketing exclusivity.

This increasingly complex web of exceptions to ordinary patent law are due to the extraordinary length of time the FDA takes to approve a new medicine. Although a U.S. patent has a term of 20 years, the time chewed up in FDA review is not taken into account. As a rule of thumb, it takes 12 to 15 years for the FDA to approve a new medicine, which results in only five to eight years of effective patent life.

The dormant designation differs from other designations in that the innovator waives any patents that extend beyond the 15-year marketing exclusivity, in exchange for extending patents that expire within 15 years. The principle behind the Dormant Therapies Act is sound. Nevertheless, there is room for improvement.

Orphan drugs and biologics are well defined. It is not clear what exactly constitutes a “dormant therapy.” According to the bill, it is dormant if “The medicine is being investigated or is intended to be investigated for an indication to address one or more unmet medical needs…” That is pretty big bucket. Senators Hatch and Bennet give examples: “Alpha-1, ALS, Alzheimer’s, epilepsy, lupus, mesothelioma, and multiple sclerosis.”

So, it is a different problem than the orphan-drug problem, which occurs when too few people suffer from a disease to make a profitable market without extraordinary protection of intellectual property. Rather, it appears to be the result of the industry’s inability to invent new medicines for certain diseases.

Alzheimer’s is a good example. Drugs specifically indicated and currently prescribed for memory loss due to Alzheimer’s are:

• Aricept™ (donepezil), which was approved in 2004 and lost exclusivity in 2010;
• Razadyne™ (galantimine), which was approved in 2001 and lost exclusivity in 2008;
• Exelon™ (rivastigmine) (Exelon), which was approved in oral form in 2000 and lost exclusivity in 2008, although a patented transdermal patch maintains exclusivity, but is threatened by litigation to strike down its patent protection;

• Namenda™ (memantine) gained approval in 2003 and became generic this year.

Although the brand-name manufacturers have launched extended-release formulations of their Alzheimer’s drugs, no truly new therapy has been launched in many years, despite high-profile, massively expensive R&D efforts. (One new patented medicine, Namzaric™, launched last December. However, it is a combination of memantine and donepezil.)

It appears Alzheimer’s drugs have about seven years of market exclusivity before generic competitors can enter the market. The Dormant Therapies Act would potentially double that period. Clearly, brand-name drug-makers would have an incentive to stretch the definition of a dormant therapy.

Defining the term “dormant therapy” more precisely would address this challenge. For example, a dormant designation could be granted to a new medicine only after a certain number of years had passed since the last approved medicine with the same indication was approved.

Also, the dormant designation does not get to the fundamental problem: That the FDA slows the rate of introduction of new therapies far beyond the optimal rate. Tacking longer exclusivity to the back end of this addresses a symptom — not a cause — of unsuccessful pharmaceutical R&D. Fortunately, other parts of the 21st Century Cures Initiative address modernizing the FDA’s regulatory activities directly.

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