KemPharm is pursuing a 505(b)(2) NDA for its lead drug candidate KP201 (benzhydrocodone hydrochloride and acetaminophen) for acute, moderate to moderately severe pain. 505(b)(2) NDAs include studies not conducted by or for an applicant, but require full safety and efficacy studies. On Friday, the company said it completed a successful end-of-Phase II meeting with FDA, and can submit a 505(b)(2) in the third quarter of 2014 without any additional efficacy, toxicology or safety data.
KemPharm’s data portfolio includes results of two recently completed pivotal studies. One showed KP201 effectively released and achieved steady-state plasma concentrations of hydrocodone, its active metabolite hydromorphone, and acetaminophen. The other showed bioequivalence; KP201 effectively released hydrocodone, hydromorphone, and acetaminophen into the bloodstream at amounts equivalent to Norco® (hydrocodone bitartrate and acetaminophen).
“We have a number of other bioequivalency studies that have to be concluded,” before KemPharm files an NDA for KP201, Travis C. Mickle, Ph.D., KemPharm’s president and CEO, told GEN.
The next clinical milestone, KemPharm says, is completion of oral and intranasal abuse liability studies in Q1 2014.
KP201 adds a ligand to hydrocodone, using a tech platform based on its Ligand Activated Therapy (LAT) technology, to create an IR drug the company says can reduce abuse potential and opioid-induced constipation—two key features KemPharm is adding as it develops other drugs. The company pipeline includes an ER hydrocodone (KP214) and an IR hydromorphone (KP511), both in preclinical phases.
Until something better comes along, hydrocodone should continue filling the niche within the pain drug segment between oxycodone and codeine.
“We see it as, if every product is now Schedule II, and there’s still this need for these types of products, then better versions like KP201 or abuse-deterrent products will do better in the marketplace. They now have equal footing with the cheaper generic,” Dr. Mickle said.
Dr. Mickle doesn’t see reclassification changing how physicians prescribe hydrocodone products, since most prescriptions are for acute pain.
OxyContin’s developer has an ongoing Phase III study to assess long-term safety of once-daily hydrocodone bitartrate tablets: “This formulation incorporates chemical and physical properties which are intended to make the tablets more difficult to manipulate for the purpose of intentional misuse and abuse by various routes of administration (e.g., snorting and intravenous (iv) injection),” Purdue Pharma spokesman James Heins told GEN.
Signature Therapeutics develops abuse-resistant opioid drugs through its Bio-MD™ platform, inserting abuse resistance into the molecule, changing its structure, then activating the same receptors as standard opioid drugs. While the company has placed priority on ER oxycodone (PF614), Signature’s pipeline includes an ER hydromorphone (PF329) that demonstrated safety, dose proportionality, and a clinically beneficial ER profile in two Phase I studies; and eight preclinical abuse-resistant opioids, three of them hydrocodone products—IR hydromorphone (PFR03321), IR hydrocodone (PF6129), and ER hydrocodone (PFR06176/177).
“We are definitely doing pre-IND work now on PF614. There are a couple of others that we may be able to have in Phase I next year. I think it’s a little bit too early to know for sure,” Wesley D. Sterman, M.D., Signature’s president and CEO, told GEN.
But not early to conclude that barring any new revelation, DEA will reclassify hydrocodone products. GPhA conceded as much by failing to comment on FDA’s action, and by pleading for flexible implementation. The only issue is how to ensure shorter prescriptions don’t lead to even more abuse—an issue FDA could address by finalizing its abuse-resistance guidance, applying it immediately to all new opioids, then over time for current products. The pain of losing lives to opioid abuse is the worst pain of all.