Praxis Bioresearch Announces Positive Results from Clinical Microdose Study in Humans Showing Oral Activation of Its Novel Prodrug Stimulant PRX-P4-003

Mittwoch, 23. Juni 2021 12:07
  • All subjects who were dosed with Prodrug PRX-P4-003 had systemic exposure of the active moiety (-)-fencamfamine suggesting robust intestinal conversion
  • As anticipated, fed subjects showed earlier systemic exposure of (-)-FCF compared to fasted subjects

SACRAMENTO, Calif., June 23, 2021 (GLOBE NEWSWIRE) -- Praxis Bioresearch, a biopharmaceutical company focused on the discovery and development of novel therapeutics for chronic central nervous system disorders, today announced that it has successfully completed a microdose study in healthy volunteers under an exploratory IND approved by FDA in January 2021.

PRX-­P4-­003 is a new chemical entity (US Patent 10,662,146) that incorporates an active isomer of fencamfamine [(-)-FCF], a well-tolerated Schedule IV stimulant. Originally developed and marketed by E. Merck KG (Darmstadt, Germany) fencamfamine has a long-established clinical profile following decades of therapeutic use in Europe and other regions. Prodrug PRX-P4-003 was specifically designed to deliver (-)-FCF selectively by the oral route thus limiting its stimulant activity to oral administration and differentiating it from other FDA approved stimulants. The profile is made possible due to PRX-P4-003 serving as a substrate of pancreatic lipase, an enzyme whose biological activity is almost entirely restricted to the gut.

PBR001 (ClinicalTrials.gov Identifier: NCT04638803) was an open-label crossover study in healthy volunteers comparing (-)-fencamfamine (FCF) plasma concentrations after oral administration of Prodrug PRX-P4-003 (100 µg) and reference drug, unmodified (-)-FCF HCL (40 µg) in the fasted state carried out in 4 healthy male volunteers. No food was allowed in the fasted subjects at least until 4 h post dose. This was followed by determination of plasma concentrations of (-)-FCF in a separate cohort of 2 volunteers following oral administration of a PRX-P4-003 (100 µg) in a fed state. Summary of preliminary results from PBR001 study is reported below.

  • (-)-FCF exposure from oral PRX-P4-003 appeared to be higher in fed compared to fasted conditions (approximately, 3-fold based on mean values for both AUC0-24h and Cmax).
  • Compared to under fasted conditions, administration of PRX-P4-003 under fed conditions results in an earlier quantifiable (-)-FCF plasma concentrations (Tmax reached earlier, 4 h vs 10 h)
  • Safety was monitored however, as is generally expected in the microdose studies, no adverse events were reported.

As anticipated the fed subjects showed earlier release of (-)-FCF and this supports one of the key steps in the prodrug conversion which is the need for a favorable intestinal milieu for its activation,” said Valentino J. Stella, distinguished professor emeritus, department of pharmaceutical chemistry at the University of Kansas and co-inventor of PRX-P4-003. Prodrug PRX-P4-003 was specifically designed to limit intravenous exposure of (-)-FCF, but not from intended oral therapeutic route, to reduce risk of abuse and safer clinical deployment”. The data is currently undergoing scientific peer review for publication and/or presentation at the upcoming scientific meetings.

“It is truly exciting to see this strong evidence of a working Prodrug PRX-P4-003 activation mechanism in man and marks the transition of Praxis Bioresearch to a clinical stage company” said Sandeep Patil, PhD, MD, chief executive officer of Praxis Bioresearch. “We remain focused on progressing this much needed innovation to safely extend the therapeutic benefits of dopaminergic intervention.”

About PRX-P4-003

PRX­-P4­-003 is a new chemical entity prodrug that incorporates an active isomer of fencamfamine [(-)-FCF], a well-tolerated Schedule IV stimulant. Originally developed and marketed by E. Merck KG (Darmstadt, Germany) fencamfamine has a long-established clinical profile following decades of therapeutic use in European and other countries. Prodrug PRX-P4-003 was specifically designed to deliver fencamfamine isomer selectively by the oral route. Thus, limiting its stimulant activity to oral administration and differentiating it from other marketed stimulants. The profile is made possible due to PRX-P4-003 serving as a substrate of pancreatic lipase, an enzyme whose biological activity is almost entirely restricted to the gut.

Stimulants such as methylphenidate and amphetamines are among the most widely prescribed classes of medications, with an estimated 90 million annual prescriptions written for a range of central nervous system conditions including attention deficit hyperactivity disorder (ADHD), narcolepsy, and binge eating disorder. According to a report issued by Persistence Market Research, the stimulant market for ADHD alone is expected to grow to $25 billion annually in 2024. However, these two stimulants are classified as Schedule II controlled drugs due to a significantly high risk of addiction and/or diversion. PRX-P4-003 is designed to pharmacokinetically deter risk of abuse while maintaining efficacy as a stimulant.

About Praxis Bioresearch

Praxis Bioresearch, LLC, is a biopharmaceutical company focused on the discovery and development of therapeutics for chronic neuropsychiatric and neurodegenerative disorders. Praxis’s lead development candidate is PRX-P4-003, a novel prodrug stimulant designed to offer the proven clinical activity of currently marketed stimulants while reducing risk of abuse and addiction.   PRX-P4-003 is being developed for the treatment of binge eating disorder and apathy in Alzheimer’s Disease. For more information visit: www.praxisbioresearch.com.

Praxis Bioresearch Forward Looking Statements

The information contained in this press release is based on current expectations and beliefs of future events. Although forward-looking statements contained in this press release are based upon what management of Praxis Bioresearch believes are reasonable assumptions, there can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Praxis Bioresearch assumes no obligation to update forward-looking statements if circumstances or management’s estimates or opinions should change except as required by applicable securities laws. The reader is cautioned not to place undue reliance on forward-looking statements.

Disclaimer: The SBIR Grant (R44MH116764) is supported by the NIMH, NIH. The content of this press release is solely the responsibility of Praxis Bioresearch and does not necessarily represent the official views of the NIH. 

Contact:
Rudi Ross
941-833-5700
info@praxisbioresearch.com


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