South Rampart Pharma announced the publication of comprehensive research in Scientific Reports detailing the mechanism of action and Phase 1 clinical trial results for SRP-001, a novel non-opioid analgesic designed to address the significant safety concerns associated with current pain medications.
Novel Mechanism Targets Brain's Pain Processing Center
The study, led by Hernan Bazan, M.D., South Rampart's co-founder and CEO, reveals that SRP-001 works by inducing the formation of N-arachidonoylphenolamine (AM404) in the midbrain's periaqueductal grey (PAG) region. This metabolite serves as a potent activator of TRPV1, playing a crucial role in the brain's response to pain. Notably, SRP-001 produces higher amounts of AM404 than acetaminophen, potentially offering superior pain relief through this targeted mechanism.
Single-cell transcriptomics analysis of the PAG region demonstrated that SRP-001 regulates pain-related gene expression and cell signaling networks, including endocannabinoid signaling, genes pertaining to mechanical nociception, and fatty acid amide hydrolase (FAAH). The compound influences critical genes encoding FAAH, 2-arachidonoylglycerol (2-AG), cannabinoid receptors CNR1 and CNR2, transient receptor potential vanilloid type 4 (TRPV4), and voltage-gated calcium channels.
Safety Profile Addresses Current Treatment Limitations
Comprehensive preclinical evaluations revealed SRP-001's favorable safety profile compared to existing pain medications. The compound lacks hepatotoxicity due to an absence of NAPQI formation and maintains hepatic tight junction integrity. As a non-NSAID, SRP-001 avoids the kidney and gastrointestinal damage risks associated with overuse of traditional anti-inflammatory drugs.
Extensive genotoxicity, safety pharmacology, and non-clinical toxicology evaluations, including ICH-compliant studies and GLP toxicity studies in two animal species, confirmed SRP-001's non-genotoxic nature. The studies showed no adverse effects on pulmonary or cardiac functions and no treatment-related adverse effects or mortality in dose-escalating studies.
Phase 1 Trial Demonstrates Clinical Promise
The completed Phase 1 randomized controlled trial involved 56 subjects receiving single and multiple ascending doses of SRP-001. Results demonstrated that the compound is safe and well-tolerated, with robust pharmacokinetics including a half-life of up to 10.1 hours. These findings support the compound's readiness for Phase 2 development across multiple pain indications.
Addressing Critical Unmet Medical Need
"The quest for innovative pain solutions is critical, driven by the extensive prevalence of acute, chronic, and neuropathic pain," said Dr. Bazan, who also serves as the John Ochsner Endowed Professor of Cardiovascular Innovation at Ochsner Health. "These pain conditions affect up to 27% of adults worldwide, including over 51 million adults in the U.S. Existing treatments such as opioids, acetaminophen, and NSAIDs pose risks of addiction and toxicity with overuse."
The current pain management landscape presents significant challenges. Chronic pain affects an estimated 51.6 million U.S. adults and nearly one-third of the global population. Neuropathic pain, resulting from nerve damage, affects approximately 7-10% of people worldwide. The opioid epidemic, characterized by 8.7 million Americans misusing prescription opioids, underscores the urgent need for safer alternatives.
Regulatory Recognition and Future Development
The FDA awarded SRP-001 Fast Track designation for acute pain in October 2023, recognizing the compound's potential to address an unmet medical need. This designation facilitates more frequent communication with the FDA and potentially expedited review processes.
South Rampart Pharma plans to advance SRP-001 into Phase 2 randomized and controlled studies for acute and neuropathic pain in the second half of 2024. The company is also developing the compound for migraine headaches, a condition affecting nearly 40 million Americans and over 1 billion people globally.
The research represents a significant step forward in developing safer pain management options that could potentially reduce dependence on opioids while avoiding the organ toxicity associated with current non-opioid alternatives.
