Product Portfolio: Pain
KP201/IR is an acetaminophen (APAP)-free formulation of its immediate release (IR) hydrocodone product, KP201. We expect this highly differentiated product candidate to feature the same abuse-deterrent properties demonstrated by KP201/APAP, our most advanced product candidate. KP201/IR would be the first IR, acetaminophen-free hydrocodone option available to physicians.
As previously reported, data from KemPharm’s intranasal human abuse liability trial (KP201.A03), which compared hydrocodone exposure following insufflation of KP201 vs. hydrocodone bitartrate (HB), demonstrated a statistically significant reduction in Cmax, a delay in Tmax, and a significant decrease in total exposure to hydrocodone, especially at early time points typically associated with increased drug liking, abuse and safety. Secondary endpoints related to drug liking, including drug liking Emax, pupillometry and ease of snorting also showed significant differences between KP201 and HB, with KP201 demonstrating lower drug liking, less pupil dilation and higher difficulty of snorting than HB.
Key Product Features of KP201/IR
If approved by the FDA, KemPharm believes KP201/IR may have many valuable product features and may provide significant benefits to patients, physicians and society, compared to other FDA-approved IR hydrocodone products:
- Molecular-based abuse-deterrent technology. Unlike formulation-based opioid abuse-deterrent approaches, KP201/IR incorporates KemPharm’s LAT platform technology to create its abuse-deterrent properties at the molecular level. This may provide a higher barrier against attempted abuse than many existing formulation-based approaches.
- No generic equivalent product. KP201/IR is a new molecular entity (NME) prodrug, and if approved, KemPharm expects it will have a lower prescribed milligram strength than the therapeutic equivalent amount of hydrocodone bitrate used in existing IR hydrocodone products. These differences will mean there will be no generic equivalent product for KP201/IR in most states, making substitution difficult at the pharmacy.
- Composition-of-matter patent protection. KP201/IR is protected by a U.S. composition-of-matter patent on KP201 that will expire, after utilizing all appropriate patent term adjustments but excluding possible patent term extensions, in 2031.
KP511/ER is an extended release (ER) formulation of KP511, KemPharm’s NME prodrug of hydromorphone, which the company is developing for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatments are inadequate. KP511/ER is designed to be an abuse-deterrent opioid product that offers equivalent efficacy to approved ER hydromorphone products.
KemPharm’s prodrug, KP511, combines hydromorphone with one or more ligands and can be formulated in both IR and ER dosage forms. KP511 is designed not to release its hydromorphone component until it is metabolized in the GI tract following oral administration. We believe KP511 is highly tamper-resistant and is stable under conditions that can potentially defeat many formulation-based abuse-deterrent technologies.
Results from a Phase 1 proof-of-concept trial of KP511(KP511.101) demonstrated comparable hydromorphone exposure between 4 mg Dilaudid™ Oral Liquid and an equimolar 8 mg dose of KP511. Based on the positive Phase 1 results, KemPharm plans to initiate a human abuse liability clinical program for KP511/ER to assess the product candidate’s tamper and extraction resistance, intranasal and intravenous abuse potential, as well as the potential to limit oral abuse and/or overdose. Additionally, KemPharm intends to investigate KP511’s potential to improve or reduce opioid-induced constipation (OIC), a common side effect of opioid therapy.
KemPharm plans to seek approval of KP511/ER under the 505(b)(2) NDA pathway.
Key Product Features of KP511/ER
Based on our preclinical data, KemPharm believes KP511/ER, if approved by the FDA, may have valuable product features and provide significant benefits to patients, physicians and society when compared to FDA-approved hydromorphone products:
- Molecular-based abuse-deterrent technology. KP511/ER utilizes KemPharm’s LAT platform technology to create its abuse-deterrent properties at the molecular level, and the company believes it may have abuse-deterrent characteristics similar to KP201/APAP.
- Oral overdose protection. In preclinical studies, KemPharm observed that hydromorphone blood levels in rats increased more slowly and to a lesser extent after oral administration of increasing excessively large doses of KP511, as compared to increasing equimolar oral doses of hydromorphone hydrochloride. We also observed that the study animals began dying from the increasing excessively large oral doses of hydromorphone hydrochloride, but never died from an equimolar oral dose of KP511. Based on the molecular structure of KP511, KemPharm believes it may be possible that the metabolic processes of releasing hydromorphone from the prodrug become saturated at excessively large oral doses. If confirmed by further studies, this could potentially mean that KP511 and KP511/ER may reduce the risk of oral overdosing by a unique mechanism that is inherent in the prodrug molecule itself.
KP746, KemPharm’s NME prodrug of oxymorphone, is designed to be an abuse-deterrent opioid product that offers equivalent efficacy to approved oxymorphone products.
Based on preclinical studies of KP746, KemPharm believes that the prodrug may offer enhanced bioavailability at typical therapeutic doses and abuse-deterrent features in comparison to standard oxymorphone. Specifically, based on preclinical studies, KemPharm believes KP746 may be highly tamper-resistant and may be stable under conditions that can potentially defeat many other abuse-deterrent technologies, suggesting greatly reduced intranasal bioavailability and minimal to no release of oxymorphone when administered intravenously.
KP746 applies KemPharm’s Ligand Activated Therapy (LAT) platform technology and has the potential to be the first approved prodrug of oxymorphone.