505(b)(2) For Formulation Changes
- Posted by: Ken Phelps
- Published on: October 20, 2009
A couple of weeks ago I was invited to present at the 2009 Nebraska Research and Innovation Conference. The theme of my talk was “The Case for Improving Existing Drugs”.
There are several factors driving people to the 505(b)(2) development pathway, a couple of which are:
- Generic cliff. By about 2017 there will be very few remaining small molecules to genericize.
- Patents are running out
- Small molecule space is mostly used up. As the chart below shows, existing effective small molecules cluster and the odds of finding something truly novel are small. Big Pharma is turning its attention to biologics.
- Pediatrics and Geriatrics. Adult (meaning people aged 17-65) drugs are scaled down for pediatrics and used ‘as is’ for geriatrics.
- 70% of the current Rx for pediatrics are off-label.
- Older people with changing metabolism and multiple drugs are simply given ‘adult’ drugs.
I’d like to focus on the fact that for many patients, existing approved drugs aren’t always effective (I’ll save the adverse events issue to alter date). Take a look at the various drug categories and you’ll see that less than half the patients benefit too much of the time:
Why is this? There are lots of factors that are outside of the drug makers control. But even if you had perfect compliance, uniform diet, controlled environment and identical genetics there are still factors that we can control. For example, take a look at the following slide which shows the disconnect between the onset of an event and the time the medication is usually given (night or day).
The slide title suggests that we have opportunities to change the formulation to improve the delivery of drugs. A good example of this is drugs to treat insomnia. In this blog we have been following Transcept’s Intermezzo (zolpidem tartrate sublingual tablet), a sublingual low dose formulation of zolpidem that has been developed for use as-needed for the treatment of insomnia when a middle of the night awakening is followed by difficulty returning to sleep. Basically, this product is formulated to release the drug several hours after ingestion.
Changing formulations is just one approach for improving the effectiveness of products in a patient population. Camargo is working with it’s clients to develop improved formulations, including cardiovascular disease, pediatric and geriatric use. There is a huge opportunity to improve existing drug products.