Statistically significant pharmacokinetic and pharmacodynamic differences of abuse potential were observed in
the KP511.A01 Study
CORALVILLE, Iowa, Jan. 09, 2017 (GLOBE NEWSWIRE) -- KemPharm, Inc. (NASDAQ:KMPH), a clinical-stage specialty
pharmaceutical company focused on the discovery and development of proprietary prodrugs, today announced the results of its
exploratory Phase 1, double-blind, single-dose, 2-treatment, 2-period, randomized, crossover study (Study KP511.A01) intended to
assess the pharmacokinetics, safety and intranasal abuse potential of KP511 Active Pharmaceutical Ingredient (API) compared to
equivalent doses of hydromorphone hydrochloride (HM API). KP511 is KemPharm’s investigational prodrug of hydromorphone for the
treatment of pain. The results of the study indicated that KP511 demonstrated statistically significant reduction in peak and
overall hydromorphone exposure with KP511 API versus HM API. The improved pharmacokinetics of KP511 resulted in meaningful,
statistically lower scores in the exploratory pharmacodynamic measures of “Drug Liking,” “Feeling High,” “Overall Drug Liking” and
“Take Drug Again” when compared to HM API.
“This study provides very strong preliminary evidence that KP511 imparts significant potential for deterring
intranasal abuse when compared to currently marketed hydromorphone products,” said Lynn Webster MD, Vice President Scientific
Affairs, PRA Health Sciences, Salt Lake City Utah, following an independent review of the Study results. “While the promising
results of this exploratory study will need to be confirmed in a pivotal intranasal human abuse potential study, they show that
KP511 may provide improvement across multiple abuse measures relative to hydromorphone. It was particularly important to see that
the ‘Take Drug Again’ endpoint was significantly lower with KP511. The ‘Take Drug Again’ measure plays an important role in the
premarket assessment of abuse deterrent technologies for predicting their performance in the real world. The current data suggest
that KP511 may be less likely snorted, which could be a potential public health benefit.”
“We are pleased with the results of the Phase 1 study of KP511, which demonstrated that KP511 may, if the
results are confirmed, provide clinically meaningful differences in intranasal abuse potential versus hydromorphone. If confirmed,
this may give us the option to develop KP511 as an extended-release and immediate-release product candidate, and, if approved,
could potentially provide an effective therapy to pain patients and offer a new hydromorphone product with meaningful
abuse-deterrent properties,” stated Travis C. Mickle, Ph.D., President and Chief Executive Officer of KemPharm. “The decrease in
mean peak hydromorphone exposure by approximately 63% combined with the delay of 30 minutes in time to peak exposure translated
into significant reduction in ‘Drug Liking,’ ‘Feeling High,’ ‘Overall Drug Liking’ and ‘Take Drug Again’ scores.”
“Given the magnitude of the potential benefit, we intend to develop both an extended release (ER) and an
immediate release (IR) version of KP511. The next phase in the development of KP511 is the completion of pivotal studies over
the next two years, leading to potentially two New Drug Applications (NDAs) being submitted as early as 2019 with anticipated
expedited review,” added Travis. “Based on our estimates, in 2015, the combined ER and IR market for hydromorphone was more
than $280 million, with over 3.2 million scripts written in that year. A market this large requires products with effective
abuse deterrence.”
Summary of the Preliminary Results from Study KP511.A01.
Study KP511.A01 was a Phase 1, double-blind, single-dose, 2-treatment, 2-period, randomized, crossover study
intended to assess the pharmacokinetics, safety and exploratory intranasal abuse potential of KP511 API compared to hydromorphone
API after intranasal administration in twenty-six nondependent recreational opioid users who reported prior insufflation
experience. The primary endpoint was pharmacokinetic evaluation of hydromorphone released from KP511 API and HM API. The secondary
endpoint was safety. The exploratory endpoint was the intranasal abuse potential.
Mean peak hydromorphone exposure (Cmax) was reduced by approximately 63% and median Tmax
for hydromorphone was delayed by 30 minutes after insufflation of KP511 API when compared to HM API. Mean overall hydromorphone
exposure with KP511 API was approximately 58% and 48% lower as measured by AUClast and AUCinf, respectively.
In addition, mean cumulative hydromorphone exposures at time points following intranasal administration of KP511 were decreased
from approximately 56% to 100% (higher reduction at earlier time points) with negligible hydromorphone plasma concentration prior
to the 30-minute time point. The results demonstrated that KP511 prodrug may release hydromorphone at a significantly slower rate
and lower extent after intranasal administration when compared to HM API. KemPharm believes the statistically significant reduction
in hydromorphone exposure translated into statistically significant differences in the exploratory pharmacodynamic measures. Mean
maximum scores (Emax) of “Drug Liking” and “Feeling High” for KP511 were approximately 11.4 and 23.4 points lower,
respectively. Additionally, mean “Overall Drug Liking” and “Take Drug Again” scores collected at 24 hours post-dose were
approximately 16.0 and 13.3 points lower, respectively. Abuse measures were assessed on bipolar and unipolar (“Feeling High” only)
visual analog scales.
In a retrospective assessment of drug preference after the last treatment, a significant majority of subjects
(17 out of 26) preferred HM API over KP511 API indicating 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 were higher (i.e.,
more severe) for KP511 versus HM API.
About KemPharm
KemPharm is a clinical-stage specialty pharmaceutical company focused on the discovery and development of
proprietary prodrugs to treat serious medical conditions through its Ligand Activated Therapy (LAT) platform technology.
KemPharm utilizes its LAT platform technology to generate improved prodrug versions of U.S. Food and Drug Administration
(FDA)-approved drugs in the high need areas of pain, attention deficit hyperactivity disorder (ADHD) and other central nervous
system (CNS) disorders. KemPharm’s co-lead clinical development candidates are KP415, an ER prodrug of methylphenidate for the
treatment of ADHD, and KP201/IR, an acetaminophen (APAP)-free formulation of the company’s immediate release (IR) abuse deterrent
hydrocodone product, KP201. For more information on KemPharm and its pipeline of prodrug product candidates visit www.kempharm.com.
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
expected features, characteristics, development timeline and potential submission of NDAs for KP511/ER and KP511/IR. These
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, and are subject to a number of uncertainties and
risks that could significantly affect current plans. Actual results and performance could differ materially from those projected in
the forward-looking statements as a result of many factors, including, without limitation, 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; obligations to third parties regarding the potential
commercialization or sale of KP511/ER or KP511/IR; and the FDA approval process, including without limitation any timelines for
related approval. KemPharm's forward-looking statements also involve assumptions that, if they prove incorrect, would cause its
results to differ materially from those expressed or implied by such forward-looking statements. These and other risks concerning
KemPharm’s business are described in additional detail in KemPharm's Quarterly Report on Form 10-Q for the quarter ended September
30, 2016, and KemPharm’s other Periodic and Current Reports filed with the Securities and Exchange Commission. 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.
Investor Contacts: Jason Rando / Joshua Drumm, Ph.D. Tiberend Strategic Advisors, Inc. 212-375-2665 / 2664 jrando@tiberend.com jdrumm@tiberend.com Media Contact: Daniel L. Cohen Executive VP, Government and Public Relations KemPharm, Inc. 202-329-1825 dcohen@kempharm.com
