Smash the pill with a hammer.
Try flicking on a lighter to melt it into a liquid.
Or maybe drop it into a glass of water to see if it dissolves.
Such actions would normally turn the pill into something a patient could snort or inject. But if it's an abuse-deterrent opioid, there's a chance none of them would work. As the name suggests, the drugs are formulated to prevent patients from using them incorrectly or illicitly. A hard outer coating may make a pill difficult to crush. An added gelling agent may make it too thick for a needle to suck up.
Abuse-deterrent formulations evolved in response to a public health crisis built over the last two decades. Research indicates these options can help curb rates of opioid misuse and overdose, yet they're far from a cure-all.
Like more traditional opioids, the products have underlying addictive properties and patients can still find ways to abuse them.
"It's really a matter of how many steps and how good of a chemist you have to be to overcome this. And with the internet, people find recipes for how to undo things," said Dave Thomas, health scientist administrator at the National Institute on Drug Abuse (NIDA). "The best abuse-deterrent formulations are the ones that would take a chemist a number of steps to undo, but they haven't found any that you can't eventually [abuse]."
Declining opioid use in the U.S., which consumes about two-thirds of the world's supply, caused the global market for legacy opioids — many of which are generic — to dip down to around $6 billion last year, according to investment bank Cowen & Co.
Meanwhile, the abuse-deterrent market in the states sat at about $2.2 billion. Abuse-deterrent opioids make up only a small fraction of the overall market, according to Cowen — about 5.1% of the 80 million prescriptions written.
Clearly, barriers remain to those seeking to get in, including cheaper generics and subsequent payer preferences, as well as the dominance of Purdue Pharma L.P.'s Oxycontin (oxycodone HCl), which gobbles up 85% of the abuse-deterrent market.
Companies like Recro Pharma Inc. and Flexion Therapeutics Inc. have also dismissed traditional opioids altogether in lieu of non-opioid analgesics, providing another source of competition.
Abuse-deterrent opioid makers have been struggling to meet the high bar for the label set by the Food and Drug Administration for over a decade, with the first to finally garner the moniker in 2013. Drugmakers are still trying to improve the technology so that it can live up to the wide range of competition in the pain space.
A tough market to break into
Intelligence firms expect the broad global pain management drug market to thrive in the coming years. BCC Research estimates a compound annual growth rate of 7.6% between 2017 and 2022, ultimately boosting the sector's total value to $52 billion by the end year. Another firm, Allied Market Research, predicts it will hit $77.1 billion in 2023.
Yet abuse-deterrent opioids, despite their added safety, haven't captured a substantial chunk of that market.
Generic opioids are largely to blame. Data compiled by the Abuse Deterrent Coalition, a group that advocates for the development of drugs with those properties, showed abuse-deterrent opioids were just 2.1% of the overall opioid analgesic market in 2016, whereas off-brand, immediate-release compounds comprised nearly 90%.
Notably, none of the 10 opioid-based painkillers to secure an abuse-deterrent profile from the Food and Drug Administration are generic. Those include Pfizer Inc.'s Embeda extended-release (morphine sulfate/naltrexone HCl) and Collegium Pharmaceutical Inc.'s Xtampza extended-release (oxycodone).
That's important, because insurers and pharmacy benefit managers tend to favor lower-cost generics over branded products when they're available.
"From a payer's perspective, you have a perfectly effective medicine — existing opioids — that are generic, that are very inexpensive relative to anything else, and they work," said Dan Cohen, chair of the ADC and head of government and public relations for KemPharm Inc., a company which tried and missed getting an abuse-deterrent label for its newly approved drug Apadaz (hydrocodone).
While the crisis has spurred uptake of abuse-deterrent drugs, Cohen argues payers know the risk of opioid abuse is low when patients receive appropriate medical management. To that end, payers tend to think of the crisis as a public health matter rather than an underlying problem with the patient-prescriber paradigm.
"Those things combined together make it very difficult for new therapies to come into place or abuse-deterrent therapies to come to the market because the payers ... don't like to pay for public health issues," he said. "When you put an abuse-deterrent in an opioid, we haven't added a thing to the therapy that the physician is prescribing to treat the patient."
Oxycontin and the rest
The dominance of Purdue Pharma is another discouragement to new entrants. Oxycontin's brand recognition and price tag, which clocks in at a fraction of other drugs in the class, have made it an intimidating rival.
"Given OxyContin's strong market position and competitive pricing, we believe that future abuse-deterrent products will have a hard time competing," analysts from Cowen wrote in a November note. "Our consultants also note that adoption of abuse-deterrent opioids is limited by the fact that they have not been established as a standard of care in the medical community."
Between generics, payers and Oxycontin, it's hard for new abuse-deterrent products, or even non-opioid painkillers, to gain much traction. Making things even harder are the roadblocks that pop up long before an FDA approval.
"Many of the novel, non-opioid analgesics are administered as pills. So you get broad systemic exposure, and all you need is one or two serious adverse events or side effects to basically halt the development of your compound," said Mike Clayman, CEO of Flexion.
"So it's a real dilemma. It's a high-risk proposition to develop systemic analgesic therapies, so much so that venture capital, relatively speaking, under-invests in analgesic development."
Generics are ruling while less risky, non-opioid options are beginning to come onto the scene. At the same time, drugs face significant barriers in securing an abuse-deterrent profile, and those that do are tasked with wrestling prescriptions away from Oxycontin.
Such challenges beg the question: is there a place for abuse-deterrent opioids in the pain market?
For some, the lack of new pain treatments in recent years actually supports the longevity of abuse-deterrent drugs, which offer another option for many patients.
"We'll probably be using opioids for the foreseeable future as part of medical treatments — not for everybody, just for some sort of treatments. And if we're using them, having abuse-deterrent formulations still helps," NIDA's Thomas said.
Others see the pain space as filled to the brim with opioids, and in need of more innovative approaches.
"I can't imagine the opioid market, abuse-deterrent or otherwise, is going to be doing anything other than contracting," Flexion's Clayman said.
"In the last decade, the division at FDA that approves analgesics has approved two novel therapeutics," he added. "Think about that: in the midst of the opioid crisis, we have two new entrants in a decade."
Either way, analysts will be watching whether these nascent abuse-deterrent opioids have staying power.
"This is a five-year-old industry, so we're at the very early stages of what we're able to do," the ADC's Cohen added.