Selected KemPharm® Prodrug Product Candidates
|Product Candidate||Parent Drug||Development Status||Next Milestone||Potential NDA Submission|
|KP415||Methylphenidate (ER)||Clinical||NDA Submission||2019|
|KP484||Methylphenidate (ER)||Clinical||PK + Efficacy Data||2019|
|KP201/IR||Hydrocodone||Clinical||IN HAL Data||2019 with Priority Review|
|KP511/ER||Hydromorphone||Clinical||POC in ER Formulation||2020 with Priority Review|
|KP511/IR||Hydromorphone||Clinical||HAL + BE Data||2019 with Priority Review|
|MULTIPLE CNS DISORDERS|
KP415 is our prodrug product candidate of dexmethylphenidate (d-MPH) with extended release properties, co-formulated with immediate-release d-MPH, being developed for the treatment of ADHD. KP415 is designed to address unmet needs with currently marketed methylphenidate ADHD treatments, including earlier onset of therapy at 30 minutes, longer duration of therapy to at least 13 hours and consistency of the therapeutic effect. In addition, KP415 may offer the possibility of a lower abuse potential.
Pharmacokinetic studies of KP415 have demonstrated an early release of d-MPH followed by sustained d-MPH exposure over the course of the day. We believe such a profile is well suited for certain ADHD patients, who may require a longer total duration of efficacy than available methylphenidate products.
Based on these attributes, we view KP415 as one of our highest priority pipeline candidates and our greatest near-term value driver. If approved, we believe KP415 has the potential to be one of the first truly differentiated methylphenidate products launched in the ADHD market in the past several years.
KemPharm’s co-lead clinical development candidate KP484 is a “super-extended release” (potential improved extended-release) methylphenidate prodrug for the treatment of ADHD. We designed KP484 for the treatment of ADHD in patients that respond best when a very long duration of therapy is required.
Preclinical and clinical studies of KP484 have demonstrated that the prodrug may produce a longer duration release of d-MPH compared to currently available methylphenidate products. Based on this release profile, we believe KP484 could enable KemPharm® to target the large and growing population of adult ADHD patients. It is estimated that approximately 10.5 million adults have ADHD, making adult patients the largest segment of the ADHD market.
Our plan is to develop KP484 in parallel with KP415 and potentially leverage data from our current and ongoing KP415 research, including pharmacokinetic and human abuse liability studies. Should the development of KP484 continue as planned, it has the potential to be the first new methylphenidate-based product being developed with the intent to address the specific needs of the adult ADHD population, which we believe remains largely underserved.
In September 2017, KemPharm® announced that it submitted an amended New Drug Application (NDA) to the FDA for Apadaz®. The FDA subsequently approved the NDA on February 23, 2018.
KP201/IR (single-entity benzhydrocodone HCl) is our acetaminophen-free immediate release hydrocodone prodrug designed for the treatment of acute pain.
Removing acetaminophen is a potentially important benefit of KP201/IR, as according to the FDA, overdoses of acetaminophen are the most common cause of drug-related liver injury. In 2011, the FDA limited the amount of acetaminophen in prescription combination products and required warnings to be added to the labels of all acetaminophen prescription products. Additionally, in July 2015, the FDA strengthened the warning label of non-aspirin NSAID products such as ibuprofen, citing an increased risk of heart attack and stroke associated with higher doses and longer use.
While there are a number of single-ingredient, IR opioids available for the treatment of acute pain (e.g., oxycodone, hydromorphone), there is currently no IR, single-ingredient, acetaminophen-free or even NSAID-free hydrocodone product approved in the U.S. KP201/IR could become the first IR hydrocodone treatment option without acetaminophen, while also imparting molecular- and formulation-based properties designed to disincentivize common forms of abuse.
KP511 (asalhydromorphone) is a prodrug of hydromorphone being developed as a new hydromorphone product with potentially abuse-deterrent properties for the treatment of pain severe enough to require an opioid. The goal is to provide KP511 in both immediate-release (KP511/IR) and extended-release (KP511/ER) dosage forms.
The potential to deter abuse of asal-HM is achieved through its chemical structure, which is designed to release hydromorphone most efficiently when metabolized in the gastrointestinal tract following oral administration. The asal-HM molecule is also designed to be tamper-resistant and demonstrate its chemically stability under conditions that may extract the active hydromorphone from certain formulation-based abuse-deterrent technologies.
In a Phase 1 intranasal study of KP511, the prodrug demonstrated statistically significant pharmacokinetic and pharmacodynamic differences in measures commonly used to assess abuse potential. Data from the study indicated statistically significant reductions in peak and overall hydromorphone exposure with asal- HM API versus hydromorphone API. The reduced hydromorphone exposure following intranasal administration of asal-HM resulted in meaningful, statistically lower scores in the exploratory pharmacodynamic measures of “Drug Liking,” “Feeling High” and “Overall Drug Liking” when compared to hydromorphone API.
Furthermore, in a retrospective assessment of drug preference after the last treatment, a significant majority of subjects (17 out of 26) preferred hydromorphone API over asal-HM API suggesting that KP511 may be less attractive for intranasal abuse. Several endpoints related to intranasal irritation including nasal burning, need to blow nose, nasal discharge and facial pain—while being mild to modest for both products—were higher (or more severe) for asal-HM API versus hydromorphone API.
KP606/IR is planned to be developed as an immediate release (IR) formulation of KP606, KemPharm’s prodrug of oxycodone intended for the treatment of moderate to severe pain. KP606, as a prodrug, combines oxycodone with one or more ligands.
KP606/IR is being designed as an IR opioid product with potential abuse-deterrent properties that will offer equivalent efficacy to approved oxycodone products. The company also plans to formulate a drug product form of KP606.
KemPharm intends to seek approval of KP606/IR under the 505(b)(2) FDA pathway.
KP746, KemPharm’s prodrug of oxymorphone, is a new molecule that is designed to be an abuse-deterrent opioid product that offers equivalent efficacy to approved oxymorphone products.
Based on in vitro studies, KemPharm® believes KP746 may be highly tamper-resistant and may be stable under conditions that can potentially defeat certain other abuse-deterrent technologies. Preclinical animal studies suggest greatly reduced intranasal bioavailability and minimal release of oxymorphone when administered intravenously.
KP746 applies KemPharm’s Ligand Activated Therapy (LAT™) technology and has the potential to be the first approved prodrug of oxymorphone.
KP303 is a prodrug of quetiapine, which is currently in preclinical development for the potential treatment of CNS disorders such as schizophrenia, bipolar disorder and major depressive disorder. The primary goal of this research is to address patient compliance and existing side effects of currently approved products.