Following up on their sobering report on drug development in depression, BIO has released another report in their State of Innovation in Highly Prevalence Chronic Diseases series.
This time, BIO tackles Pain and Addiction.
The first item which caught our eye was the total number of FDA NCEs approved for pain over the past decade.
Milnacipran (for fibromyalgia) and tapentadol (opioid for chronic pain).
All other approvals have been reformulations (mainly abuse deterrent) of existing drugs.
Second, the probability of a Phase I candidate making it to approval is only 2% for pain candidates, compared to ~10% overall.
To no one’s surprise, venture investment in this therapeutic space is practically zero.
It’s really amazing to think back 20 years when COX 2 inhibitors were some fo the first blockbusters in our industry, only to have that market largely collapse once we fully understood the problems associated with widespread COX inhibition.
Indeed, we are still treating pain, especially chronic severe pain, with the same compounds and mechanisms of action used during the US Civil War.
However, all is not lost.
In fact, the pain pipeline looks pretty good, at least from a therapeutic perspective.
Of the 220 ongoing clinical programs for pain indications, 125 of them are for novel candidates, and nearly 90% of those are pursuing non-opioid targets.
A significant number of these programs are targeting neuropathic pain, which makes a great deal of sense given the rapid growth in diabetes and diabetic neuropathy.
So while the innovation is there, it is likely that many of these companies may find it difficult to secure financing to advance these programs (both venture and internal/corporate financing).
Indeed, a high clinical failure rate, coupled with a highly genericized market, will make it difficult to build attractive business cases for companies developing novel, innovative pain candidates.
Old Dogs, New Tricks
Recognizing the need to reduce opioid use, a number of studies are revisiting the idea of using NSAIDs (alone and in combination) to treat moderate to sever pain.
For example, Chang, et al. found “…no clinically important differences in pain reduction at 2 hours with ibuprofen and acetaminophen or 3 different opioid and acetaminophen combination analgesics.”
Other analyses conclude that the combination of ibuprofen 200 mg and acetaminophen 500 mg is “…one of the strongest pain relievers available.”
We cannot deny that acute and chronic NSAID use has its issues. Indeed, careful monitoring is essential to manage their well-known side effects.
Fortunately, a number of companies, including one of our own clients, are developing novel technologies to address these side effects without resorting to polypharmacy-based approaches.
We have not even touched on the issue of opioid abuse, misuse, and the widespread morbidity and mortality this is causing. That’s a broader societal issue which needs a multi-pronged approach to resolve.
However, financing the development of novel non-opioids, coupled with the development of new NSAID-based candidates, will provide patients with better alternatives to Civil War-era pain relievers, while simultaneously addressing the broader societal problem.