FDA
15th August 2016

FDA panel supports approval of new “abuse-deterrent” opioid oral tablets

The combination of benzhydrocodone HCl (KP201) and acetaminophen (APAP) act as a pro-drug that is metabolically activated in the gastrointestinal tract. Therefore, these tablets are being marketed as an abuse-deterrent formulation since non-intended usage, such as administration through the nasal or intravenous route, have no pharmacologic opioid effects.

FDA panel supports approval of new “abuse-deterrent” opioid oral tablets

On May 5, 2016, a joint panel of the Anesthetic and Analgesic Drug Products (AADPAC) and the Drug Safety and Risk Management Advisory Committees (DSaRM) supported approval of Apadaz, an opioid drug sponsored by KemPharm Inc. Apadaz is an immediate-release (IR) benzhydrocodone HCI/acetaminophen oral tablet indicated for short-term (maximum of 14 days) handling of acute pain.

The combination of benzhydrocodone HCl (KP201) and acetaminophen (APAP) act as a pro-drug that is metabolically activated in the gastrointestinal tract. Therefore, these tablets are being marketed as an abuse-deterrent formulation since non-intended usage, such as administration through the nasal or intravenous route, have no pharmacologic opioid effects.

The main experiments conducted to evaluate the efficiency and abuse-deterrent properties of Apadaz included pharmacokinetics clinical trials, human abuse potential studies, and laboratory in vitro manipulation and extraction studies. In addition, epidemiological studies helped to compare the abuse pattern/potential to other opioid products. KemPharm’s results indicated a lower hydrocodone exposure using intranasal and intravenous administration compared to the closest competitor, Norco.

Two questions were directed to the panel by the Food and Drug Administration (FDA): 1) Is the drug effective in the treatment of acute pain? and 2) Does the drug warrant abuse-deterrent labeling? The committees voted in favor of Apadaz (16 to 4) for its proposed indication of managing acute pain since the data satisfied bioequivalence to reference products. The clinical evidence presented no new or greater risk of intravenous abuse as compared to current available therapies. However, the committees voted against Apadaz (2 to 18) being labeled as an abuse-deterrent drug due to unconvincing data in nasal route experiments that demonstrated slight relevance.

The committees expressed their concern over giving Apadaz an abuse-deterrent label by claiming that the evidence was inconclusive and carries the risk of misguiding people. Committee member Dr. Tobias Gerhard stated “we have to remain critical when being presented with data for such products, and I think here we haven’t seen the type of evidence that would suggest that this product really makes a difference compared to the available IR products.” In support of this decision, Dr. Charles Emala expressed his concern in allowing “a false sense of security to prescribers that could actually accelerate the volume and number of these pills prescribed.”

Although hydrocodone combination products are the most common opioid analgesics, the FDA has yet to approve an IR abuse-deterrent opioid drug. Currently, there are six approved opioid products with abuse-deterrent designation, but they all have extended-release (ER) profiles.

The agency is not obligated to follow its panel’s recommendation, but normally does so.

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