Viewpoint: the case for longer drug exclusivity

I have dealt in the past with an analysis of the decline in patent-based drug exclusivity, pointing out that data exclusivity is becoming increasingly important. However, the time has come to raise the issue more broadly: the case for longer terms of commercial protection, in the interests of better medicines should be heard. In the end, the issue is this: patents and data exclusivity are a grand bargain between the regulatory systems and innovators, so that in return for investing in R&D, commercial rewards can accrue in an environment protected form competition.

The patent system has, over time, evened out at offering a period of around 20 years from filing. There is far less uniformity around data exclusivity protection, with periods varying from 5 years in the USA, to 10 years in Europe for a new non-biological drug. Other periods apply for orphan drugs and for new indications; it is too complicated to provide a complete picture in this short article. The central difference between the tow forms of protection is that data protection applies from approval of a medicine, whereas patent protection must be filed ‘at risk’, long before it is known whether a product can make the grade.

Clearly, innovators are always pushing for longer periods of exclusivity, and generic companies for shorter. In 2010, the biopharmaceutical industry managed a significant victory in attaching a term of 12 years for biologic data exclusivity onto the Obamacare health reforms in the USA. In so doing, the balance of commercial advantage shifted further in the direction of biological over small molecule pharmaceuticals: I have also dealt with this before.

These periods were set against a backdrop of pharmaceutical development times of, say, 10-12 years. This is a reasonable estimate of the time taken to discover and develop a new drug from inception to market for its first indication. Of course, there are many who fail to be successfully developed because of an errant choice for that indication. The recently announced deal between the NIH and various pharmaceutical companies to repurpose some of the stalled development candidates in their pipeline may address that issue.

But, for many, the identification of the ideal therapeutic ‘home’ for a compound may only come a long time after its initial discovery. As an extreme example, Biogen-Idec’s new product BG-12 (dimethyl fumarate) is coming to the US market nearly two centuries after the compound was originally discovered. Ironically, it is probably only doing so because no previous use for the compound has been registered there (although it has been used in dermatitis, but only in Germany): had a previous use been identified, for a similarly formulated product, it is a strong probability that the off-label generic problem would have precluded the development of this compound for MS.

Another case caught my eye recently, that of alemtuzumab (Campath-1H). This originated from the laboratory of the world’s first monoclonal antibodies (Milstein and Kohler in Cambridge) and was first approved for the treatment of chronic lymphocytic leukaemia. It works by binding to the CD52 receptor, which is present on the surface of mature lymphocytes but not the stem cells from which they are produced.

Shortly after it was first discovered, its effects in multiple sclerosis were identified. In MS, alemtuzumab depletes the body of lymphocytes, which causes a reprogramming of the immune system. The new, modified repertoire of lymphocytes no longer regards myelin and nerves as foreign, thus quelling the autoimmune pathophysiology of MS. This can result in the prevention of a relapse in disease for MS patients lasting from 3 to 5 years, a dramatic result. In addition, many patients experience an improvement in disability which is not seen for standard (interferon) treatment. However, immune reprogramming is an inherently risky process, which in roughly one patient in three results in the development of another autoimmune reaction, normally against the thyroid gland.

What does this all mean? Well, the complexities of alemtuzumab in MS resulted in a clinical development period stretching from the early 1990s to 2011 for the top line results from the second of the two Phase III trials to be announced. So, even when the mechanism of a drug and its potential application in a new disease is well understood, the clinical development can take far longer than our current system of patents and data exclusivity was designed for.

Fortunately, alemtuzumab is a biologic. So, even though approved for leukaemia for over 10 years, generic versions are not currently on the market, and the new use can be commercialised in a monopolistic environment. It is interesting to compare this situation with BG-12, which like most small molecules will probably become generic within its first decade of commercial life. Thereafter, the approval of a new use for the same product (i.e. without any formulation changes) will be very unlikely.

I believe we are left with an increasingly complex landscape of patent and data exclusivity protection that is not fit for purpose. Within the database that we have populated over the years, there are over 1600 associations of new indications with either mechanism or compound, and without novel thinking, the vast majority of these will never be commercialised.

In order to optimise profitability, the following behavioural shift is encouraged among innovators:

  1. R&D of biological products is preferred, even though these agents normally do not cross the blood brain barrier and are disfavoured for CNS disease
  2. secondary uses for existing drugs are commercially unattractive even though such programmes are less costly and quicker than conventional new chemical entity projects, and are associated with less chance of adverse toxicology.

Neither of these behaviours is in the best interests of patients or payers (especially since biologics are much more expensive than small molecule drugs). The first necessary step in improving the situation is to grant small molecules the same period of data exclusivity as biologics in the world’s largest pharmaceutical market. On its own this will not address behaviour #2; for that a separate remedy is dicussed, in the next blog.

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