KemPharm Announces Positive Topline Results from Intranasal Human Abuse Potential Trial of KP415 Prodrug

NDA Filing for KP415 Anticipated As Soon As First Quarter of 2019 Following Successful Completion of HAP Program

Highlights of KP415.A02 Intranasal HAP Trial Results:

• Mean Drug Liking (E_max) of intranasal KP415 Prodrug (serdexmethylphenidate) was statistically significantly lower than d-methylphenidate hydrochloride

CORALVILLE, Iowa, Sept. 17, 2018 (GLOBE NEWSWIRE) -- KemPharm, Inc. (NASDAQ:KMPH), a specialty pharmaceutical company focused on the discovery and development of proprietary prodrugs, today announced topline results from its intranasal (IN) human abuse potential (HAP) clinical trial of serdexmethylphenidate (SDX, a prodrug of d-methylphenidate, or KP415 Prodrug), the major active pharmaceutical ingredient (API) in KP415, KemPharm’s investigational product candidate for the treatment of ADHD. In the IN HAP trial (KP415.A02), SDX produced significantly lower scores on the primary endpoint, maximal Drug Liking (E_max), and other abuse-related endpoints, compared to intranasal d-methylphenidate hydrochloride, indicating that SDX is not efficiently converted to active d-methylphenidate when snorted.

“In designing SDX, one of KemPharm’s objectives was to develop a prodrug of d-methylphenidate that could address the key unmet need among ADHD patients and prescribers of lower abuse potential compared to current stimulant products,” said Travis Mickle, Ph.D., President and Chief Executive Officer of KemPharm. “Today’s positive results from the IN HAP trial, combined with the previously reported intravenous and oral HAP data, indicate that SDX has lower abuse potential than relevant d-methylphenidate comparators when misused intranasally, intravenously, or orally at high doses. We believe the totality of these findings should position KP415 as differentiated from currently available methylphenidate-based ADHD products.”

Mickle added, “With the KP415 efficacy and HAP programs complete, KemPharm now has the key components of the data package for the KP415 New Drug Application (NDA), which we expect to file as early as the first quarter of 2019. Simultaneously, we remain actively engaged in a competitive partnering process for KP415 and KP484, which we are targeting for completion by year-end.”

KemPharm will present the data from all three HAP trials, as well as tampering study results, to the U.S. Food and Drug Administration (FDA) as part of its human abuse potential assessment for SDX in the KP415 New Drug Application (NDA). During the review process, the FDA will recommend a controlled substance schedule for SDX to the Drug Enforcement Agency (DEA). If KP415 is approved, the DEA must subsequently confirm the schedule for SDX, and KemPharm believes that the entirety of the data may support a lower schedule compared to other currently available methylphenidate-based ADHD products. Furthermore, since the FDA has required KemPharm to conduct all three HAP trials, KemPharm anticipates that data from these trials may likely be included in the label.

About the KP415.A02 Trial:

The KP415.A02 IN HAP trial was the last of three human abuse potential trials required by the FDA and was conducted with SDX, the prodrug component in KemPharm’s two lead investigational product candidates, KP415 and KP484. KP415.A02 was a single-center, Phase 1, randomized, double-blind, placebo-controlled, single-dose, 3-way crossover trial to determine the abuse potential and pharmacokinetics of an 80 mg dose of SDX API compared to an equimolar dose of 40 mg d-methylphenidate hydrochloride API following intranasal administration in recreational stimulant users. The trial consisted of a screening phase, a drug discrimination phase, and a treatment phase. Subjects were enrolled in the treatment phase if they were able to differentiate between the effects of a single intranasal dose of d-methylphenidate hydrochloride and placebo in the drug discrimination phase. Forty-five (45) subjects completed all three treatment periods of the treatment phase.

In the trial, statistically significant reductions in the means for maximal (E_max) Drug Liking were observed for SDX (80 mg, 71 points) when compared to an equimolar dose of d-methylphenidate hydrochloride (40 mg, 93 points). In addition, secondary endpoints of Take Drug Again (E_max) and Overall Drug Liking (E_max) that assess drug effects retrospectively, along with other secondary endpoints including Feeling High (E_max) and Good Effects (E_max), were statistically significantly lower for SDX as compared to d-methylphenidate hydrochloride.

In summary, in this trial, intranasal administration of SDX produced pharmacodynamic effects that were significantly diminished compared to d-methylphenidate hydrochloride as measured by multiple endpoints that are commonly used to assess human abuse potential.

These results reflect preliminary topline data and are subject to further analysis. The full data and detailed results will be submitted for presentation at future scientific conferences and publication in peer-reviewed journals.

KP415 Human Abuse Potential Program Design and Data Review:

The KP415 HAP program was designed by KemPharm to assess the abuse potential of SDX in comparison to d-methylphenidate via the intravenous, intranasal and oral routes of abuse. The program included three FDA required clinical trials, KP415.A01, KP415.A02 and KP415.A03 as well as tampering studies. KP415.A01 and KP415.A03 trial results are summarized below.

KP415.A01 – Oral HAP Trial

In the KP415.A01 oral HAP trial, which was designed to determine the abuse potential and pharmacokinetics of 120 mg and 240 mg doses of SDX in capsules compared to an 80 mg dose of Focalin^® XR and a 60 mg dose of phentermine following oral administration in recreational stimulant users, abuse-related effects produced by SDX were significantly reduced compared to Focalin^® XR, and at some dose levels, lower or similar to phentermine, a schedule IV controlled substance, as measured by multiple endpoints that are commonly used to assess human abuse potential. Importantly, KemPharm observed statistically significant reductions in maximal Drug Liking (E_max) for SDX at doses of 120 mg and 240 mg (63 and 64 points, respectively) when compared to twice the maximum daily clinical dose of Focalin^® XR (80 mg, 82 points), and for the 120 mg dose of SDX when compared to twice the maximum daily clinical dose of phentermine (60 mg, 80 points).

KP415.A03 – IV HAP Trial

In the KP415.A03 intravenous (IV) HAP trial, which was designed to measure the pharmacokinetics and pharmacodynamic effects of SDX, d-methylphenidate hydrochloride and placebo after IV administration in recreational stimulant users, abuse-related effects produced by SDX were significantly reduced in recreational stimulant users when compared to d-methylphenidate hydrochloride. Importantly, SDX demonstrated statistically significant differences compared to d-methylphenidate hydrochloride in the primary endpoint, maximal Drug Liking (E_max), and no statistical difference compared to placebo. Secondary endpoints including E_max of Overall Drug Liking, Feeling High, and Good Effects were also significantly decreased for SDX compared to d-methylphenidate hydrochloride, and similar for SDX compared to placebo. 

About KemPharm:

KemPharm is a specialty pharmaceutical company focused on the discovery and development of proprietary prodrugs to treat serious medical conditions through its proprietary LAT^TM (Ligand Activated Therapy) platform technology. KemPharm utilizes its proprietary LAT platform technology to generate improved prodrug versions of FDA-approved drugs in the high need areas of ADHD, pain and other central nervous system disorders. KemPharm’s co-lead clinical development candidates are KP415 and KP484, both based on a prodrug of d-methylphenidate, but with differing extended-release/effect profiles for the treatment of ADHD. In addition, KemPharm has received FDA approval for APADAZ^®, an immediate-release combination product containing benzhydrocodone, a prodrug of hydrocodone, and acetaminophen. For more information on KemPharm and its pipeline of prodrug product candidates visit www.kempharm.com or connect with us on Twitter, LinkedIn, Facebook and YouTube.

Caution Concerning Forward Looking Statements:

This press release may contain forward-looking statements made in reliance upon the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements include all statements that do not relate solely to historical or current facts, and can be identified by the use of words such as “may,” “will,” “expect,” “project,” “estimate,” “anticipate,” “plan,” “believe,” “potential,” “should,” “continue” or the negative versions of those words or other comparable words. These forward-looking statements include statements regarding the clinical development and expected features and characteristics of KemPharm’s product candidates, including KP415, the partnering process for KP415 and KP484, the expected timing of the NDA submission for KP415, and the potential label for KP415. Forward-looking statements are not guarantees of future actions or performance. These forward-looking statements are based on information currently available to KemPharm and its current plans or expectations Actual results and performance could differ materially from those projected in the forward-looking statements as a result of many factors, including the risks and uncertainties associated with: KemPharm's financial resources and whether they will be sufficient to meet KemPharm's business objectives and operational requirements; results of earlier studies and trials may not be predictive of future clinical trial results; the protection and market exclusivity provided by KemPharm's intellectual property; risks related to the drug discovery and the regulatory approval process; the impact of competitive products and technological changes; and the FDA approval process under the Section 505(b)(2) regulatory pathway, including without limitation any timelines for related approval. Risks concerning KemPharm’s business are described in detail in KemPharm’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2018, filed with the Securities and Exchange Commission (SEC) on August 10, 2018, and KemPharm’s other Periodic and Current Reports filed with the SEC. KemPharm is under no obligation to (and expressly disclaims any such obligation to) update or alter its forward-looking statements, whether as a result of new information, future events or otherwise.

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