It’s estimated that 27.5% of people globally are affected by pain. While they might be effective, existing analgesics each have their issues. Acetaminophen/paracetamol (Tylenol, Panadol) can be toxic to the liver, and non-steroidal anti-inflammatory drugs or NSAIDs (aspirin, ibuprofen, and others) can damage kidneys and cause stomach ulcers. Meanwhile, opioids are notoriously addictive and responsible for a high number of deaths caused by overdose.
Then, there are conditions for which treatment with traditional analgesics can be ineffective. Nerve pain, or neuropathy, is one example; chronic pain is another. Determined to uncover a new analgesic with the potential to treat these hard-to-treat conditions and avoid the health risks associated with classic analgesics, researchers at South Rampart Pharma developed SRP-001. The drug has been tested in a Phase 1 clinical trial, yielding very promising results.
“The quest for innovative pain solutions is critical, driven by the extensive prevalence of acute, chronic, and neuropathic pain,” said Hernan Bazan, South Rampart’s co-founder and CEO and the study’s lead and corresponding author. “Existing treatments such as opioids, acetaminophen, and NSAIDs pose risks of addiction and toxicity with overuse.”
Before conducting human trials, the researchers examined SRP-001’s effect on animals. When acetaminophen is broken down in the body, it causes the brain’s pain region to produce AM404, which makes brain cells retain the naturally occurring pain-reducing cannabinoid anandamide. In mice, SRP-001 caused the brain to produce higher amounts of AM404 than acetaminophen. Examining the drug’s effect on gene expression in the brain’s pain region, they found that both drugs activated the same signaling pathways and regulated key pain-related genes.
The problem with acetaminophen is that when it’s broken down, it generates N-acetyl-p-benzoquinone-imine, thankfully abbreviated to NAPQI, which is toxic to the liver in high doses. It’s the reason that acetaminophen needs to be taken only as directed and, therefore, has a narrow therapeutic window. That means there’s a fine line between a therapeutic dose and an overdose. Indeed, acetaminophen is the most common cause of drug-induced liver injury in the US, with half of all cases caused by people inadvertently overdosing.
In the current study, mice given SRP-001 in a dose equivalent to a toxic dose of acetaminophen showed no signs of liver toxicity. And, whereas 70% of the mice given a toxic acetaminophen dose died, none of the mice given an equivalent dose of SRP-001 did. This was because, the researchers discovered, SRP-001 didn’t lead to the production of NAPQI.
When they tested mice and rats’ pain responses following the administration of SRP-001, the researchers found that it produced an analgesic effect comparable to acetaminophen across acute and chronic pain conditions in young and old animals. SRP-001 also produced similar fever-reducing properties as the existing drug.
The researchers recruited 56 healthy volunteers aged 18 to 55 for their human studies. They were randomized to receive either an oral suspension of SRP-001 or a placebo. Comprehensive testing of participants’ vital signs and laboratory results – including kidney and liver function – showed no abnormalities, demonstrating that SRP-001 was safe. Moreover, no serious adverse events were reported, meaning it was well-tolerated. The drug was found to have a half-life of up to 10 hours.
Because SRP-001 is not an NSAID, it doesn’t run the risk of damaging the kidneys or gastrointestinal tract. And it’s not an opioid, so it lacks the potential for abuse. The promising results from this Phase 1 trial have motivated the researchers to continue evaluating their novel drug, particularly its ability to treat nerve pain.
“Armed with known mechanisms for pain relief in the brain and compelling Phase 1 randomized trial data, we look forward to advancing SRP-001 into Phase 2 randomized and controlled studies for acute and neuropathic pain in the second half of 2024,” Bazan said.
In October 2023, the US Food and Drug Administration (FDA) granted South Rampart Pharma a Fast-Track designation for SRP-001 as a treatment for acute pain. The designation facilitates the development of new therapies designed to fill an unmet medical need and speeds up the review process.
The study was published in the journal Scientific Reports.
Source: South Rampart Pharma