Aptinyx’s NYX-2925 treatment candidate continues to significantly reduce the levels of a brain biomarker associated with pain severity, called glutamine (Glx), in people with fibromyalgia, top line results of a Phase 2 pilot trial show.
The findings also showed improvements in patient-reported pain, as well as a reduction in fibromyalgia’s impact on daily living.
“The statistically significant effects on both pain-related brain activity and patient-reported clinical measures elegantly demonstrates that NYX-2925 is acting in the brain to alter pain processing, leading to pain alleviation,” Norbert Riedel, president and CEO of Aptinyx, said in a press release.
“The results with NYX-2925 are compelling and compare very favorably with the effects of approved fibromyalgia drug treatments we previously evaluated in separate and similar studies,” added Daniel Clauw, an investigator in this trial and a professor at the University of Michigan.
NYX-2925 is an oral therapy that acts to modulate the NMDA receptor, which is key in neuronal communication, and is involved in regulating pain signals in the brain and spinal cord. NYX-2925 alters neural cell communication, and is seen as a potential therapy to lessen pain and other symptoms associated with chronic pain.
In preclinical models of different neuropathic pain conditions, NYX-2925 showed robust efficacy, and a favorable safety profile. Then, in a Phase 1 clinical trial (NCT02834741) with healthy individuals, NYX-2925 was well-tolerated across a wide range of doses.
Now, researchers report top-line results from the ongoing Phase 2 trial (NCT03249103), which is testing the efficacy and safety of daily oral treatment with 20 mg and 200 mg of NYX-2925, as well as a placebo, over six weeks in people with fibromyalgia.
A total 23 participants first received daily doses of placebo, followed by 20 mg of NYX-2925 and 200 mg of NYX-2925 each for two weeks. A one-week follow-up occurs after the last week of treatment.
Researchers evaluated the treatment’s effects on markers of central pain processing, assessed using advanced imaging techniques (primary outcome) and patient-reported outcomes (secondary outcomes).
Glutamine is a brain activity marker that is increased in specific brain regions of people with fibromyalgia. Investigators previously had identified a correlation between its increased levels and pain severity.
In agreement with early results, NYX-2925 significantly reduced the levels of glutamine in critical brain regions that regulate pain, compared with the placebo. Furthermore, the decrease in glutamine levels in one of these specific brain regions correlated with reduced clinical pain. The connections between brain regions involved in processing chronic pain also were decreased by NYX-2925.
The therapy also improved multiple patient-reported outcomes. Average and worst daily pain, as measured using the 10-point Numeric Rating Scale — in which 0 indicates no pain, and 10 indicates the worst pain imaginable — showed a 1.09 point and 0.98 point reduction, respectively, from the start of the trial (baseline) with NYX-2925 treatment.
NYX-2925 also reduced scores on the Revised Fibromyalgia Impact Questionnaire (FIQR), which measures the impact of fibromyalgia on daily living — using a 100 point scale, with the higher scores indicating worse fibromyalgia — by 9.6 points compared to baseline.
Finally, scores on the Patient Reported Outcomes Measurement Information System Fibromyalgia (PROMISFM) scale — another fibromyalgia symptom scale that ranges from 16 to 80, with a higher score noting worse symptoms — decreased by 5.4 points compared to baseline after NYX-2959 treatment.
The trial showed that NYX-2925 appeared to be well-tolerated, and no serious side effects were identified.
“Knowing the challenges these patients face and the limited therapeutic options, it is very encouraging to see these results on both imaging and clinical measures. The therapeutic potential indicated by these findings highlights the importance of advancing NYX-2925 in development as a therapy for patients suffering from fibromyalgia,” said Lesley Arnold, a trial investigator and a professor at the University of Cincinnati.
“These data meaningfully inform further clinical development, and I look forward to working with Aptinyx as the team moves into its next Phase 2 study,” Arnold added.
Based on these results, Aptinyx said it will begin enrollment in a larger, 12-week, randomized, placebo-controlled study in patients with fibromyalgia in the second half of 2019. That study will evaluate patient-reported outcomes as the primary endpoint, the company said.
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