SEOUL, South Korea I March 16, 2023 I OliPass Corporation, an RNA therapeutics platform company, 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. “The ongoing Phase 2a study has been estimated to be statistically fully powered, once the study is completed in 90 patients as initially planned,” said Dr. Shin Chung, CEO of OliPass. “Given that OLP-1002 possesses disease-modifying activity to down-regulate neuropathic hypersensitization, the analgesic efficacy of OLP-1002 shall increase upon repeated dose,” added Dr. Chung.
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. 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,” noted Dr. Chung.
Hundreds of millions are still painfully suffering from chronic or refractory pain. OLP-1002 has been estimated to create a market potential exceeding 50 billion USD per year owing to its strong efficacy, excellent safety, and vast therapeutic scope.
[About OLP-1002] OLP-1002 is an SCN9A antisense PNA and selectively inhibits the expression of Nav1.7 sodium channel in neuronal cells. OLP-1002 replicates much of the phenotype of people with a null mutation in the SCN9A gene. OLP-1002 shows an attomolar (10-18M) in vitro potency and broadly distributes to tissues, which would be responsible for its very small therapeutic dose and long therapeutic duration as seen in the ongoing Phase 2a trial. Unlike small molecule inhibitors of Nav1.7, OLP-1002 possesses disease-modifying activity by down-regulating neuropathic hypersensitization.
[About OliPass Corporation] OliPass Corporation is a public biotech company listed in KOSDAQ in South Korea (ticker: KQ244460). The company is developing RNA therapeutics based on its proprietary oligonucleotide platform called OPNA (Olipass Peptide Nucleic Acid). OPNA was derived from PNA by rational chemical modifications to show good cell permeability and ultra-strong affinity for RNA. For therapeutic intervention, OPNA potently binds to target pre-mRNA, induces exon skipping, and yields mRNA splice variant. Unlike other types of RNA therapeutics, OPNA does not require formulational aid for in vivo therapeutic activity.
SOURCE: OliPass Corp