The success of Orexigen’s (OREX) weight loss drug, Contrave, with the FDA advisory panel highlights an important area in drug development - repositioning. Orexigen accomplished this by combining the off-patent drugs bupropion and naltrexone in a novel, single-pill, fixed-dose formulation. Bupropion is an antidepressant and smoking cessation drug while naltrexone is used to treat alcoholism and drug addiction.
This strategy is rarely used by Big Pharma companies, which prefer to pursue development of new chemical entities. But interestingly enough, three separate biotechs have developed just such products, all successfully completing clinical trials, each with significant sales potential.
Avanir (AVNR) has received regulatory approval with its PBA treatment, Nuedexta, a combination of dextromethorphan and quinidine. Vivus (VVUS) developed an efficacious fixed dose combo of topiramate and phentermine for obesity but received a CRL. It is, however, expected to gain approval sometime in 2011. And of course, there’s Orexigen’s combo diet pill, recommended by the FDA panel and now awaiting approval.
That is an amazing feat of coincidence, or perhaps it’s a wake-up call; after all, three diet drugs went up for approval, the one now furthest behind is the novel entity from Arena Pharmaceuticals (ARNA).
The most often cited example of a repositioning success story is that of Thalidomide - going from a withdrawn treatment for morning sickness to cancer therapy. But the three drugs from Avanir, Vivus, and Orexigen, if successful, will surely go down in the record books as testimony to the possibilities available with drug repositioning of generics.
It is an old saw now to say that Pharma research productivity is declining. High failure rates and long development time lines result in the cost of each new drug reaching $1 billion dollars (estimates range from $800 million to well over $1 billion depending on the source). Even with this enormous cost, only 10% of a typical Pharma research budget is set aside for drug repositioning and reformulation . Often, this work is part of a pipeline’s lifecycle management, not the pursuit of truly novel indications.
To escape the current cycle of patent expirations, Big Pharma has seemingly tried every trick in the book: inlicensing, outsourcing, cost cutting, mergers, generics, and geographic expansion. What is needed most is a way to continue innovating while managing the costs of discovery and development.
Finding new uses for old drugs fits that bill perfectly. The American Medical Association (AMA) estimates between 40-60% of prescriptions in the US are for off-label uses, indicating the potential of each drug to have multiple uses. While it may take between 12 to 17 years to develop a novel compound, this period can be reduced to between 3 to 12 years for a repositioned product . This is in large part due to the considerable amount of data already compiled on older compounds. Repositioned drugs may also receive a somewhat easier FDA review process due to its long record of in-human use. If such data is used for the regulatory filing, a 505[b] application can save significant time and money.
There are certainly risks involved in repositioning generics, particularly with IP issues. But if companies can show the use of an old pharmaceutical product is new, surprising, or unexpected, they should be able to secure patent protection . Additional layers of protection may come from proprietary formulations- such as the combination drug from Orexigen as well as a period of data exclusivity provided by the US and EU.
There is a large reservoir of generics in the marketplace. Some entrepreneurial biotechs are now sifting through them with a fine-tooth comb. Perhaps Big Pharma should follow suit.
- Research and Development Strategies, Thomas Reilly and Nicole Yost
- Getting The Drug Repositioning Genie Out Of The Bottle, Life Science Leader
- Exploiting Newly Discovered Indications of Known Therapeutics, Melissa Hunter-Ensor, Ph.D, George W. Neuner, and Peter F. Corless of Edwards Angell Palmer & Dodge LLP