In the case of abuse-deterrent products, the FDA has waded into some deep water and it seems the water continues to deepen. Clarity around what FDA really wants and expects from such products remains murky at best. In the latest news , “Acura Pharmaceuticals Inc. (NASDAQ: ACUR) announced today that the US Food and Drug Administration (FDA) has denied on procedural grounds Acura’s appeal of the position taken by Division of Anesthesia, Analgesia, and Addiction Products (DAAAP) that abuse by snorting of hydrocodone with acetaminophen products lacks relevance. Relevance is defined in FDA’s January 2013 Draft Guidance on the evaluation and labeling of abuse deterrent opioids to be a “known or expected” route of abuse for that product.” (see complete announcement here).
As we have blogged about previously, there are a number of issues associated with abuse-deterrent formulations that the Agency and industry are wrestling with. For example, FDA’s approval of Zohydro (single entity hydrocodone bitartrate extended-release capsules) (the controversy that FDA has, in my opinion, handled well), continues to make front page news but now that the innovator has indicated that it has submitted an abuse-deterrent form of the product for FDA approval, the storm seems to have calmed down a bit.
The many facets of this particular space raise various questions that the relatively short marketing of these types of products has not really had time to generate sufficient data to answer. Will these products actually reduce abuse? Does the abuse-deterrent property of the product keep the product from being abused, or can the property be defeated by the abuser? Is it FDA’s role to assure that a product that may be a Godsend to a patient in intractable pain have a duty to remove the product from the market for a “safer” abuse-deterrent version of the drug (and safer only if not used under the conditions specified in the approved labeling). The mission of drug approval and drug diversion and misuse have (in this instance) seems to have met at a crossroad. From a public health perspective, it is a noble gesture to approve a drug that may have a high abuse potential in an abuse-deterrent formulation but it is also a public health imperative that physicians have an appropriate arsenal to fight end of life or severe intractable pain to reduce suffering.
So in Acura’s case, it appears that FDA did not buy the argument that their specific abuse-deterrent characteristic lacked relevance. With abuse-deterrent Oxycontin ER Tablets, FDA made the call in Purdue’s favor by making a determination that the non-abuse deterrent product no longer had an acceptable risk/benefit ratio and ordered that all equivalent products must also be abuse-deterrent; however, with Opana ER, Endo was not as lucky and FDA permitted the continued marketing of the non-abuse deterrent versions.
Clearly, only time will tell if FDA’s actions add up to a positive benefit to public health. Will we see continued rise in heroin usage and subsequent increased death rate from a totally non-regulated, cheaper alternative like heroin? Will epidemiological studies support FDA’s actions and drive their decision making? Will physicians be able to adequately treat their pain patients? Will enforcement need to be increased to assure that inappropriate distribution at the wholesale and retail levels and that pill mills are kept in check?
Will innovator companies use switches to abuse-deterrent products to regain market share from currently approved non-abuse-deterrent generic products? Will there be a move to apply these same abuse-deterrent technologies to other therapeutic areas (e.g., benzodiazepines, ADHD drugs, etc.) to keep generics at bay, while new patents on the abuse-deterrent product are in force? How does this change the economic picture for generic players, pharmacy benefit managers, governmental payors, and health benefit plans?
These are only a handful of concerns that the healthcare market will face when addressing this hot topic. The answers are slow in coming and the landscape is very uncertain. But I am glad the discussion is being held.
