The FDA has approved a combination of acetaminophen and the prodrug benzhydrocodone (Apadaz, KemPharm, Inc.) that the manufacturer believes is “a differentiated product for the short-term management of acute pain.”
The FDA approved the immediate-release product for the short-term (no more than 14 days) management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. “Based on its unique properties, we firmly believe there is a commercial pathway for Apadaz in what is a very high-volume market,” said Travis Mickle, PhD, KemPharm’s President and Chief Executive Officer.
Apadaz is a fixed-dose combination of 6.67 mg benzhydrocodone HCI (a prodrug of hydrocodone equivalent to 7.5 mg hydrocodone bitartrate) and 325 mg acetaminophen. The prodrug consists of hydrocodone plus benzoic acid. The Drug Enforcement Administration has signaled its intent to schedule Apadaz as a Schedule II controlled substance. KemPharm says the approved label concludes that the clinical program “did not demonstrate abuse-deterrence by current measurement standards.”
The FDA rejected the new drug application for Apadaz in 2016, leading to a company appeal and resubmission of the application in September 2017. The FDA had said intranasal abuse of the opioid-based product was a relevant concern, Reuters reported.
Apadaz was developed from KemPharm’s proprietary LATTM (Ligand Activated Therapy) platform technology. “KemPharm believes Apadaz is unique among prescription opioids in that it contains a prodrug that is chemically inert, or inactive, on its own,” the company says. “When ingested, enzymes in the gastrointestinal tract cleave the ligand from the prodrug (benzhydrocodone) and release the parent drug (hydrocodone), which can then exert its therapeutic effect.”
The approval of Apadaz via the 505(b)(2) pathway was based in part on pharmacokinetic studies with Vicoprofen, Ultracet, and Norco in which Apadaz demonstrated exposure to hydrocodone and acetaminophen that is expected to result in therapeutic effects equivalent to currently approved IR hydrocodone/acetaminophen combination products when administered orally as intended.
KemPharm is a specialty pharmaceutical company focused on the discovery and development of proprietary prodrugs that are designed to be differentiated versions of widely prescribed, currently approved drugs.