Drug Repositioning

Summary

The industry is facing multiple problems - discovering new chemical entities is costly, time consuming and above all difficult. For smaller companies and fledgling firms repositioning is an opportunity to reduce some of the risks associated with de novo drug development.

For a company planning to go the repositioning route, the strategy presents potentially fewer risks and substantially lower development costs. More importantly this approach is, possibly, a quicker route to market.

However, whilst repositioning as a strategy presents numerous opportunities and is more risk-adverse than de novo drug discovery, there are also a number of caveats:

• Access to approved or late stage compounds and their associated data packages can be difficult, especially if the compound is still under patent protection
• The very nature of repositioned drugs means that they may be affected by generic competition
• There are doubts as to whether the pharmacopoeia can sustain the repositioning pipeline

This report covers the evolution of R&D, analyses current trends in R&D metrics and examines common repositioning strategies. It also presents a series of repositioning case studies, before going on to explore trends in drug repositioning, including the repositioning landscape and opportunities.

Rising drug development costs, diminishing product pipelines, stricter regulations and greater generic competition are placing increasing pressures on your industry. With fewer products being approved and the blockbuster model showing signs of age, companies will need to focus on maximising revenues from existing products. Accordingly, lifecycle management will become increasingly ubiquitous.

Lifecycle management currently has two major goals: either to prolong the exclusivity period of a drug or to increase the market size by targeting new patient populations.

These 'evergreening' strategies involve a variety of methods: new indications, extending patent periods by reformulations or developing new delivery mechanisms, and introducing combination products.

In contrast to the 'evergreening' of only blockbuster drugs, a recent trend has seen speciality firms, biopharmaceutical companies and start-ups using lifecycle management tactics to develop novel uses for existing or abandoned drugs with medium to high sales potential.

The strategy of finding new uses for old or discontinued drugs is currently known by a plethora of common terms, including repositioning, repurposing, reprofiling and rediscovering. For the purposes of this review the term repositioning will be used.

Repositioning has recently been embraced by an increasing number of speciality and biotech companies as one of the primary routes to market.

So why repositioning? The industry is facing multiple problems - discovering new chemical entities is costly, time consuming and above all difficult. For smaller companies and fledgling firms repositioning is an opportunity to reduce some of the risks associated with de novo drug development.

For a company planning to go the repositioning route, the strategy presents potentially fewer risks and substantially lower development costs. More importantly this approach is, possibly, a quicker route to market.

For the investor, investments in life sciences can be problematic. A typical venture capital fund has a 10-year lifecycle. But this does not correspond with the time frame needed to build a successful drug development/biotech company. In contrast, repositioning drugs offers a fast way to create value and get products to market.

The emergence of focused drug repositioning companies reflects the industry's need for risk reduction and the reality that not all drugs have to be blockbusters.

Repositioning as a risk reduction model now has many distinguishing characteristics. In comparison to the reformulation model or the in-licensing model, repositioning often utilises cutting-edge discovery technologies. Indeed, many of the emerging repositioning companies use proprietary discovery platforms to extract new therapeutic properties and mechanisms from old or abandoned drugs.

Focused drug repositioning companies with proprietary technology platforms also dispels the notion of repositioning as just a 'rehashing' of old or discontinued compounds.

The companies currently focusing on repositioning are using a number of strategies. These strategies are distinguished by unique proprietary approaches and technologies.

The emergence of focused repositioning companies has stimulated these areas of research. More importantly, these companies are applying emerging technologies that are usually confined to de novo research. The application of cutting-edge technology to old drugs has enabled many of these young companies to bring products rapidly into clinical development.
However, given the relative youthfulness of repositioning as a focused strategy, it still remains to be seen whether the approach will prove viable and most importantly, profitable. As with many trends observed in the biotech industry, repositioning may well turn out to be transient. Where repositioning is different is that the companies operating in this area are following precedents already set by big pharma. The success of Merck & Co's finasteride, Pfizer's sildenafil and Celgene's thalidomide are clear examples that success is possible.

Whilst repositioning as a strategy presents numerous opportunities and is more risk-adverse than de novo drug discovery, there are also a number of caveats.

Repositioning companies often start with approved or late stage compounds. However, a key bottleneck may be access to these products and more importantly, accessing the associated data packages, especially if the compound is still under patent protection.

In addition, the very nature of repositioned drugs means that they may be affected by generic competition. With off-patent drugs, the IP position needs to be strong and in the majority of cases, the products are protected by method-of-use claims (the so-called 'Swiss Claim'). However, there is still the risk of doctors prescribing off-label.

One question that has been raised time and again is whether the existing pharmacopoeia can sustain the repositioning pipeline. Moreover, with so many compounds gathering dust on their shelves, it would not be surprising to see mainstream pharmaceutical companies reviewing the potential of repositioning.

Indeed, some biotechs with the requisite technologies, rather than entering the repositioning arena as de facto repositioning companies, are offering their services to big pharma.

Contents

• Chapter 1 Drug Repositioning: Old Drugs, New Uses
  • 1.1 The Evolution Of R&D
  • 1.1.1 Proteomics And Bioinformatics
  • 1.1.2 Screening
  • 1.1.3 In Silico Testing
  • 1.1.4 The Future
  • 1.2 Current Trends In R&D Metrics
  • 1.2.1 The New Cost Of R&D
  • 1.2.2 R&D Productivity
  • 1.2.3 Industry Average Drug Development Times And Attrition Rates
  • 1.3 Mean Drug Development Times And Attrition Rates By Therapeutic Area
  • 1.4 Lifecycle Management
  • 1.5 Drug Repositioning
  • 1.5.1 The Repositioning Concept
  • 1.5.2 The Repositioning Option
  • 1.6 Common Repositioning Strategies
  • 1.6.1 Therapeutic/Biological Model Insight
  • 1.6.2 Agnostic Screening
  • 1.6.3 Rescreening The Pharmacopoeia Against New Targets
  • 1.6.4 Virtual Discovery
• Chapter 2 Repositioning Case Histories
  • 2.1 Marketed Repositioned Drugs
  • 2.1.1 Therapeutic/Biological Model Insight
  • 2.1.2 Agnostic Screening
  • 2.2 Case History 1: Thalidomide
  • 2.3 Case History 2: Fluoxetine + Olanzapine
  • 2.4 Case History 3: Omeprazole Powder
  • 2.5 Case History 4: Milnacipran
  • 2.6 Case History 5: Doxycycline
  • 2.7 Case History 1: Chlorpromazine And Pentamidine (Cr-026)
• Chapter 3 Trends In Drug Repositioning
  • 3.1 The Repositioning Landscape
  • 3.1.1 Arachnova
  • 3.1.2 Btg
  • 3.1.3 Collegium
  • 3.1.4 Combinatorx
  • 3.1.5 Cypress Biosciences
  • 3.1.6 Dynogen
  • 3.1.7 Foamix
  • 3.1.8 Hypnion
  • 3.1.9 Sention
  • 3.1.10 Sosei
  • 3.1.11 Vectura
  • 3.1.12 Vela
  • 3.1.13 Vicus
  • 3.2 Repositioning Opportunities
  • 3.2.1 Pharma Markets, 2004-2008, By Major Indications
  • 3.3 Regulatory Landscape
  • 3.3.1 505 (B)(2) Ndas
  • 3.4 The Ip Landscape
  • 3.4.1 Patent Strategies For Drug Repositioning