OliPass Corporation disclosed that OLP-1002, a selective inhibitor of Nav1.7 sodium ion channel, showed strong analgesic efficacy and long therapeutic duration according to interim findings from a placebo-controlled double blind multicenter Phase 2a study in chronic osteoarthritis patients with moderate to severe pain in Australia. In the Phase 2a study designed to evaluate 90 osteoarthritis (OA) patients in total, patients are subjected to pain assessment for 6 weeks following a single subcutaneous injection of 1 microgram (mcg) OLP-1002, 2 mcg OLP-1002 or placebo (vehicle only). An interim analysis was carried out for the first 30 patients (10 patients per group) completed the pain assessment primarily by WOMAC Pain and VAS.

The average WOMAC Pain score of 2 mcg group gradually decreased and reached the lowest in day 43 (6 weeks) post dose. The observed % decrease in day 43 was 55% from the baseline. In the meantime, placebo effect peaked in day 15 (2 weeks) post dose and then gradually subsided to a decrease of 26% from the baseline in day 43.

Consequently, 2 mcg group and placebo started differentiating from day 22 (3 weeks) post dose. The observed difference between 2 mcg OLP-1002 and placebo in day 43 is regarded quite large compared to conventional pain killer's efficacies in OA pain studies. The difference was either slightly short of significance (p-value 0.07 by t-test) or significant (p-value 0.011 by Wilcoxon test).

The current sample size (10 patients per group) of this interim analysis would be too small for OA pain trials to draw reliable conclusions by statistical analysis. VAS scores showed a similar trend to WOMAC Pain scores. Taken these interim findings together, 2 mcg is the therapeutic dose eliciting strong efficacy with an injection frequency of once every two months.

OLP-1002 is being evaluated to pin down the therapeutic dose in OA patients which is translated further into the therapeutic dose for peripheral pain in general. OLP-1002 is still considered ideal for a broad range of chronic or refractory pain, to name a few, diabetic neuropathic pain, trigeminal neuralgia, chemotherapy-induced pain, fibromyalgia, cancer pain, and so on. People with a null mutation in the SCN9A gene encoding Nav1.7 sodium ion channel subtype were found insensitive to pain but with other sensory functions undisturbed.

A selective inhibitor of Nav1.7 has been implicated to safely treat pain. Unfortunately, there are ca 10 sodium channel subtypes structurally indistinguishable with small molecule inhibitors. Inhibition of Nav1.5 subtype, for example, may cause life-threatening heart arrhythmia.

Nav1.7 selectivity really matters to safety. Despite a huge number of Nav1.7 selective small molecule inhibitors have been evaluated, none have manifested strong efficacy and good safety in patients. OLP-1002 would be the first Nav1.7 selective inhibitor manifesting strong efficacy and good safety.