Briefing documents prepared for FDA advisors considering potential approval of Kempharm Inc.'s abuse-deterrent prodrug of hydrocodone, Apadaz (KP-201/acetaminophen), on Thursday appeared supportive of the 505(b)(2) filing, while simultaneously acknowledging the complexity of making recommendations on the drug's label in light of the critical public health issues on the road to safer opioid analgesics.

Panelists at the meeting, which will involve a joint session of the Anesthetic and Analgesic Drug Products Advisory and Drug Safety and Risk Management Advisory committees, will be asked to discuss potential routes of abuse for the immediate-release (IR) product, language in the label and one voting question: Should Apadaz be approved for short-term management of acute pain?

If approved, Apadaz would be the first IR hydrocodone formulation with abuse-deterrent properties on the market, potentially positioning it to capture a significant slice of the 120 million prescriptions for IR hydrocodone/acetaminophen (APAP) prescriptions dispensed annually in the U.S.

The FDA, which granted priority review for the new drug application in February, has assigned a June 9 PDUFA date.

To determine whether or not to advise FDA approval of Apadaz, panelists will be asked to discuss three points. First, they'll consider whether the data presented for hydrocodone and acetaminophen combination drug products in the company's application support that the nasal route of abuse is relevant for Apadaz, a questions that pertains to the Kempharm's claim for the product representing a benefit over hydrocodone/acetaminophen products.

Next, they'll be asked whether there are sufficient data to support a finding that KP201 has properties that can be expected to deter abuse and to comment on support for deterrent effects for each of the three possible routes of abuse: Oral, nasal and intravenous (I.V.).

Finally, if the panelists favor the FDA approving Apadaz, they'll be asked to discuss whether there is sufficient data to support the inclusion of language regarding I.V. or nasal abuse-deterrent properties in the drug's label.

"Prescription opioid products are an important component of modern pain management. However, abuse and misuse of these products have created a serious and growing public health problem," wrote Sharon Hertz, director of the FDA's Division of Anesthesia, Analgesia, and Addiction Products, in a letter prefacing the briefing documents. "One potentially important step towards the goal of creating safer opioid analgesics has been the development of opioids that are formulated to deter abuse."

Although the FDA issued final guidance in April 2015 to assist industry in the development of opioid drug products with potentially abuse-deterrent properties, there are currently no single-entity or combination (opioid/non-opioid) immediate-release analgesics labeled with abuse-deterrent properties as described in the guidance, Hertz noted.

The abuse-deterrent space is complex, and no single drug is completely capable of tackling it. "We'll be the first to say that, with approval and good commercialization, we are not going to solve the prescription drug abuse problem," Dan Cohen, Kempharm's executive vice president for government and public relations, told BioWorld Today. "What we will be able to demonstrate, we believe, is that this product will deter abusers, especially naïve abusers who tend to be the ones who start with these combination products."

In evaluating the FDA's assessment of the potential abuse routes the committee will discuss, Cowen and Co. analyst Ken Cacciatore observed that Kempharm successfully demonstrated that Apadaz is more difficult to solubilize and therefore inject, but that issues of nasal and other abuse routes may be more complex. That said, he concluded that "the product appears approvable," especially in light of bioequivalence data to branded Norco.

"We believe that there will be sufficient differentiation that will provide clinicians reasons to prescribe KP201 over other significantly more abusable options," Cacciatore concluded.

Given the immense number of prescriptions for hydrocodone/APAP products written each year in the U.S. and the high level of abuse involving the combination, "prima facie, there's just a clear need for these immediate-release products to have some abuse-deterrent properties and technologies," said Kempharm's Cohen. "Part of our argument to the panel tomorrow will be that this drug provides 100 percent of the benefit to the patient that they would get from the same drug without our prodrug technology in it, but it reduces the availability of the product and helps deter those who would manipulate it from abusing the product."

Kempharm shares (NASDAQ:KMPH) fell 92 cents, or 5.6 percent, to close at $15.67 on Wednesday.