A survey of more than 200 physicians found that 31% think opioid antagonists is the abuse-deterrent formulation that is most needed to combat the opioid abuse epidemic--an issue that's been implicated in the startling rise of the death rate of middle-aged white Americans without a college degree.
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What type of abuse- deterrent formulation is most needed? |
Number (out of 214 respondents) |
| Opioid antagonist/agonist combination | 66 (31%) |
| Physical or chemical barrier | 48 (22%) |
| Novel delivery system | 34 (16%) |
| Aversion | 33 (15%) |
| Prodrug | 14 (7%) |
| Other or combination of above | 19 (9%) |
FierceDrugDelivery supplied the question to Quantia MD, the provider of a physician engagement platform that counts one-third of U.S. doctors as its members.
Out of 214 physicians, 66 said opioid antagonists/agonists are the most needed formulation. Opioid antagonists are substances that interfere with the euphoria associated with drug abuse. The deterrents would generally be released and activated only if the product is manipulated, such as during crushing or snorting.
Opioid antagonists are being deployed to treat addicted patients, but have not yet been combined with a traditional opioid agonist pain reliever as an abuse deterrent. An attempt at making such an abuse-deterrent formulation in the 1960's and 70's failed because the medicine could be crushed and combined with another drug, and then injected.
The FDA just granted Braeburn Pharmaceuticals and Camurus Fast Track Designation for their weekly and monthly subcutaneous injectables of buprenorphine to treat addiction. Along with partner Titan Pharmaceuticals ($TTNP), Braeburn is awaiting word from the FDA for its subdermal implant that delivers the antagonist buprenorphine as a maintenance treatment for opioid addiction. In addition, BioDelivery Sciences ($BDSI) sells transmucosally delivered Bunavail to treat drug addiction. The drug is delivered via the inner cheek. It also contains buprenorphine and naloxone.
Most efforts at abuse deterrence have been focused on physical or chemical barriers to manipulation, a strategy that 22% of respondents preferred. Also, 16% called for a novel delivery systems such as an injections or implants, 15% said the most needed formulations are those that contain aversive substances which produce unpleasant effects if a product is manipulated or used at high dosage, 7% responded prodrug (or formulations in which the drug becomes active only after being metabolized within the body) and finally, 9% said another, unspecified formulation or combination approach is needed.
The categories of formulations chosen were those listed in FDA's guidance document on the evaluation and labeling of abuse-deterring opioids, which also contains a more detailed explanation of the terms (as well details about how they are regulated).
When asked about the impact of abuse-deterrent formulations, 54% of respondents said they would have some impact if adopted, 15% said they would have a significant impact and 30% said they would have minimal impact.
Indeed, the survey respondents commented that the higher price of expensive formulations will limit their adoption due to stingy insurance company reimbursement. Others said prescribing guidelines and usage limitations are what's actually needed.
Still, drug companies continue to invest heavily in abuse-deterrent formulations, and with good reason. Most provide physical or chemical barriers to abuse.
The NIH is helping to fund Acura Pharmaceuticals' Phase I Limitix formulation, which contains chemical and physical barriers that make it difficult for the opioid tablet to be crushed and snorted or injected into the body. Meanwhile, Egalet ($EGLT) is commercializing Oxaydo, an immediate-release oral formulation of oxycodone that's designed to avert abusive snorting via an inactive ingredient that may cause nasal burning.
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| Margaret Hamburg |
And Purdue Pharma is aggressively marketing the abuse-deterrent opioid agonist Hysingla ER. Rival Zohydro ER also deploys physical and chemical barriers to abuse, but has not yet secured FDA approval to market the formulation as abuse deterrent. The original non-abuse deterring formulation of Zohydro sparked controversy. Massachusetts made an unsuccessful attempt at banning the product, whose approval led some to call for the resignation of former FDA commissioner Margaret Hamburg.
Opioid (and heroin) drug abuse is becoming an increasingly prominent issue nationwide, as evidenced by the primary campaigns of various presidential contenders. Non-abuse deterrent opioids like Purdue Pharma's potent Dilaudid remain predominant and easily available.