Selected KemPharm® Prodrug Product Candidates
|Product Candidate||Parent Drug||Development Status||
|Potential NDA Submission|
|KP484 (Licensed)||Methylphenidate (ER)||Clinical||Initiation of Efficacy Trial
(TBD by Partner)
|As early as 2023|
|KP922 (ROFN)||Amphetamine (IR and ER)||Preclinical||IND Submission
|Stimulant Use Disorder|
|KP879 (ROFN, ROFR)||Methylphenidate (ER)||Clinical||Phase 1 Data
|KP1077 (ROFN, ROFR)||Methylphenidate (ER)||Preclinical||Phase 2/3
KP484 is KemPharm’s co-lead clinical development candidate being developed for the treatment of ADHD in patients that respond best when a very long duration of therapy is required. Similar to KP415, KP484 also consists of serdexmethylphenidate (SDX), KemPharm’s prodrug of d-methylphenidate (d-MPH).
Preclinical and clinical studies of KP484 have demonstrated that the prodrug may produce a longer duration release of d-MPH compared to the most prescribed 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 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.
KemPharm has identified a series of prodrugs of amphetamine that have demonstrated a range of potentially advantageous pharmacokinetic profiles in nonclinical studies. These prodrugs may allow the development of product candidates that fit various market opportunities. Potential benefits of these products may include customizable release profiles and low abuse potential. As with other prodrugs developed by KemPharm, these product candidates also have the potential for long-lived composition of matter patent protection. The lead candidate will be developed for the treatment of ADHD, although these prodrugs may also be amenable for the development of products with indications in other therapeutic areas for which stimulant-like effects are desirable.
Stimulant Use Disorder
KemPharm is developing KP879 as an extended-duration, agonist replacement therapy for the treatment of Stimulant Use Disorder (SUD). KP879 utilizes serdexmethylphenidate (SDX), KemPharm’s prodrug of d-MPH which is also the primary active pharmaceutical ingredient of KP415 and KP484, the company’s co-lead clinical development product candidates which are intended for the treatment of ADHD.
SUDs include those marked by abuse/misuse of cocaine, methamphetamines, prescription stimulant products that contain methylphenidate or amphetamine, and numerous designer stimulants including, for example, 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone) (“bath salts”). According to the Substance Abuse and Mental Health Services Administration (SAMHSA), in 2016, among Americans older than 12 years, there were approximately 1.9 million current users of cocaine, 667,000 users of methamphetamine, and 1.7 million current misusers of prescription stimulants. To date, there are no FDA-approved medications for the treatment of SUD.
Among the many potential drug therapies that have been studied for the treatment of SUD, medications with CNS stimulant-like properties have shown the most benefit. It is believed that by enhancing dopamine signaling in key brain areas, agonist replacement therapies may decrease craving and use of illicit stimulants, promote restorative sleep, and increase retention time of patients in substance abuse therapy. However, prior agonist replacement therapies have been limited in part by concerns of their own abuse potential among the stimulant-abusing population.
Based on information gathered during the KP415 and KP484 development programs, KemPharm believes that SDX has pharmacokinetic properties that are desirable as an agonist replacement therapy for the treatment of SUD. Specifically, KemPharm observed that SDX provided a gradual onset followed by long duration of d-MPH exposure, while also exhibiting the potential for a reduction in abuse-related effects. Given these properties, KemPharm is advancing KP879 as a potential first-ever therapeutic treatment for SUD.
KemPharm is advancing KP1077 as a potential first-ever therapeutic treatment for Idiopathic Hypersomnia (IH). IH is an incapacitating neurological disorder marked by significant detrimental effects on nighttime sleep as well as daytime sleepiness/wakefulness. IH is considered a rare disease (11/100,000), sometimes confused with narcolepsy due to the similarity in daytime symptoms. There are currently no approved therapies for IH but narcolepsy treatments are commonly employed off-label to manage symptoms. These off-label treatments include GHB, methylphenidate, amphetamine, and modafinil. However, there remains significant unmet needs with currently available treatment options.
KemPharm has identified a prodrug of an undisclosed parent drug that it believes has significant potential for treating IH while also addressing unmet needs with currently available therapies that are employed off-label in this patient population. As with other prodrugs developed by KemPharm, this product candidate has the potential for long-lived composition of matter patent protection.
APADAZ® (benzhydrocodone and acetaminophen) is a combination of benzhydrocodone, a prodrug of the opioid agonist hydrocodone, and acetaminophen that was approved by the U.S. Food and Drug Administration (FDA) on February 23, 2018. KemPharm announced its entry into a definitive collaboration and license agreement with KVK Tech, Inc. for the U.S. commercial rights of APADAZ on October 30, 2018. The commercial launch for APADAZ is planned for the second half of 2019.
Click here to learn more about Apadaz.
AZSTARYS® (serdexmethylphenidate and dexmethylphenidate capsules, for oral use, CII) is an FDA-approved, once-daily product for the treatment of attention deficit hyperactivity disorder (ADHD) in patients age six years or older. AZSTARYS® consists of serdexmethylphenidate, KemPharm’s prodrug of d-methylphenidate (d-MPH), co-formulated with immediate release d-MPH.
The complete approved prescribing information for AZSTARYS® is provided below: