Algiax Pharmaceuticals’ non-opioid candidate has achieved “clinically meaningful” pain reduction in a mid-stage trial of people with peripheral post-surgical neuropathic pain, marking another success in an area that has recently been gaining momentum despite a challenging history.
More than a quarter of patients treated with the German biotech’s GABAA-receptor modulator, dubbed AP-325, saw at least 50% pain reduction compared with 11% of placebo patients, according to data shared with
Endpoints News
. The Phase 2a study enrolled almost 100 patients across 27 trial sites in Germany, Spain, the Czech Republic, Belgium and France.
Further, over half the patients in the treatment cohort didn’t need any rescue pain medication versus 21% of placebo patients. AP-325 was well-tolerated with no serious adverse events observed and zero central nervous system symptoms such as drowsiness or sedation, chief scientific officer Guido Koopmans told Endpoints in an interview.
The drug’s strong safety profile has to do with the fact that it acts peripherally, compared with standard-of-care options that affect the central nervous system. “What we basically do in the periphery [of the nervous system] is restore inhibitory control, because that’s one of the aspects that is lost in neuropathic pain,” Koopmans said. “We bring back this inhibitory control and that triggers a cascade of other things that happen like neuroplasticity, which causes the [analgesic] effect.”
Algiax is now looking at a range of options for further development of AP-325, including a large Phase 3 study as well as pathways for more “rapid” advancement. CEO Ingo Lehrke did not disclose the company’s timeline for starting a potential Phase 3, but said in the interview it is focused on gathering detailed feedback from trial investigators and refining a clinical plan.
The Phase 2a data suggest it’s possible to develop new safe and effective treatments for chronic neuropathic pain — an area that has seen a “graveyard of failed products” over the past two decades, Lehrke says. In December, Vertex’s NaV1.8 pain signal inhibitor suzetrigine performed
similarly to placebo
in a Phase 2 chronic pain study despite technically passing the test. The drug fared better in the acute pain setting, where it
secured an FDA approval
last week.
In 2019, Aptinyx’s NMDA receptor modulator
flunked a mid-stage trial
in diabetic peripheral neuropathy. Three years later, Lexicon Pharmaceuticals’ AAK1-targeting asset
disappointed
in a Phase 2 proof-of-concept study in postherpetic neuralgia. From 2000 to 2020, the
chances
of a Phase 1 pain drug going on to win approval was just 10%, and even that was primarily driven by reformulated opioids.
But pharma companies and investors are starting to show renewed interest in non-opioid pain relief. In 2023, Eli Lilly licensed an angiotensin II type 2 receptor inhibitor for neuropathic pain from Confo Therapeutics in a deal featuring
$40 million
upfront. That same year, Hoba Therapeutics — which was founded by Novo Holdings — raised
$25 million
in a Series A to help advance its recombinant human meteorin asset.
