The placebo group was significantly better than the 1 mcg group on average for the whole 6 weeks. 4 out of the 20 patients in the placebo group showed a pain reduction of 78% or higher on average for 6 weeks. 10 out of the 20 patients in the placebo manifested a pain reduction of 50% or higher on average for 6 weeks.

The efficacy profile of the 2 mcg group was strikingly different from the profile observed in the interim analysis. Judging from the efficacy profiles, the 1 mcg group looks more like placebo. VAS Findings from Extension Study: The 2 mcg group showed pain reduction reaching a plateau of 27% in week 4 and afterwards.

In case of the placebo group, pain reduction reached a plateau of 43% in week 4 and afterwards. The 1 mcg group showed a pain reduction of 19% stably maintained from week 1 and afterwards. The placebo group was not significantly different from the treatment groups.

Based on the efficacy findings by WOMAC Pain and VAS, however, the 1 mcg group in this extension study looks more like placebo. 8. Excessive Placebo Effect from Phase 1b Study: Overt placebo effect has not been unprecedented with OLP-1002. In a Phase 1b study in OA patients conducted in Australia again with Novotech, patients were subcutaneously administered with placebo, 5 mcg OLP-1002 or 10 mcg OLP-1002 two times per week for two weeks, and then subjected to pain assessment for six weeks post the first dose.

At the end of the study, i.e., Day 45, the observed pain reduction by WOMAC Pain was 21% for the 5 mcg group (n = 13), 32% for the 10 mcg group (n = 11), and 55% for the placebo group (n = 10). The placebo group was significantly (p < 0.05) more effective than the 5 mcg group by WOMAC Pain in Days 25, 32 and 45. In the meantime, the observed pain reduction by VAS was 11% for the 5 mcg group, 20% for the 10 mcg group and 47% for the placebo group on average during the period of Day 33 to 45.

The placebo group was significantly (p < 0.05) more effective than the 5 mcg group by VAS on average during the period of Day 33 to 45. Judging from the efficacy readouts, however, the 5 mcg group looks rather like placebo. [Loss-of-function Mutation in SCN9A gene & Safe Pain Killer] 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. Lack of safe and effective pain killers triggered the outbreak of opioid crisis.

Opioid crisis is getting worse and taking lives of more than 100,000 victims each year. The urgency and importance of identifying safe and effective pain killers can never be overemphasized.