2. Polmacoxib drug- Hisaka - by Ortho.pptx

polmacoxib

1. Polmacoxib

2. Confused state Cox 2 selective Which NSAID to choose? Nonselective/ Preferential NSAID COX 2 selective NSAID

3. Therapy gap Decrease in PGi2( inhibitor of platelet aggregation and a powerful vasodilator.) & increase in thromboxane (inducer of platelet aggregation and arterial constriction ) is most likely mechanism causing CV events due to coxibs. CV events are compound specific rather than being a class effect characteristic of all coxibs. Therefore, there remains an unmet medical need for new alternative coxibs that do not cause cardiovascular events Clinical Therapeutics/Volume 44, Number 1, 2022

4. Polmacoxib - The next generation NSAID Polmacoxib is the first, tissue-selective and once-a-day coxib with a novel mode of action Unlike other coxibs, Polmacoxib has a dual mode of action: Potent inhibitor of COX-2 Potent inhibitor of carbonic anhydrases (CAs). (CA type 1 & II) CA are the enzymes that catalyze bidirectional conversion of CO2 & water (H2O) into bicarbonate (HCO3-) and protons (H+) and are involved in numerous physiological processes. CA I and  CA II  are highly expressed in the RBCs , GI tract and kidneys

5. Polmacoxib -Approval status Recently approved in India Approved for osteoarthritis treatment in South Korea & Turkey and MENA region covering 19 countries

6. Tissue specific cox inhibitor In Joint in OA patients In other tissues in OA patients Inflammation Acidosis COX2 Carbonic Anhydrase No Inflammation Abundant carbonic anhydrase Minimal COX2 Clin Orthop Surg. 2017 Dec;9(4):439-457 In tissues like OA joints Where COX-2 is high ,polmacoxib binds preferentially with cox2 sparing CA In tissues, Where CA is higher, polmacoxib binds with CA,sparing COX 2

7. Imp features of Polmacoxib Biochemical and Biophysical Research Communications (2016) 1e6

8. Phase III Clinical Study Summary Clin Orthop Surg. 2017 Dec;9(4):439-457

9. Phase III Study: Study Title & The Objectives Study Title: A Double-blind, Randomized, Multicenter, Active- and Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of Polmacoxib in Osteoarthritis Patients Objectives: The objective of the 6-week Efficacy Study – To evaluate the safety and non-inferiority of the analgesic efficacy of polmacoxib 2 mg vs. celecoxib 200 mg, and the analgesic superiority of polmacoxib 2 mg vs. Placebo The objective of the 18 week Extension Study –To collect a total of 24 weeks of safety data for those subjects who agreed to continue into the extension . Study Details Clin Orthop Surg. 2017 Dec;9(4):439-457

10. Polmacoxib 2 mg achieves a quicker onset of relief from the signs and symptoms of osteoarthritis compared to celecoxib 200 mg . ( At 3 weeks) Polmacoxib 2 mg was relatively well tolerated and demonstrated efficacy superior to placebo and noninferior to celecoxib after 6 weeks of treatment in patients with OA. Results obtained during the 18-week trial extension with polmacoxib 2 mg were consistent with those observed during the 6-week treatment period, indicating that polmacoxib can be considered safe for long-term use Phase III Study: Conclusions (6-week Treatment Period) Conclusions Clin Orthop Surg. 2017 Dec;9(4):439-457

11. Comparative advantage with COX-2 inhibitors & Other NSAIDS Naproxen, Ibuprofen, diclo Etoricoxib Celecoxib Polmacoxib Classification Non preferential NSAID COX-2 inhibitor COX-2 inhibitor Tissue selective COX-2 inhibitor Indication Osteoarthritis & Others Osteoarthritis Osteoarthritis & Others Osteoarthritis Amount 75–2,400 mg/day 30 mg 200 mg 2mg Dose 2-4 times a day Once a day Once a day Once a day Half life 6-12 hrs 22 hrs 11 hrs 5 days Efficacy Non-inferior to traditional NSAID & Celecoxib Non-inferior to traditional NSAID Non-inferior to traditional NSAID and Celecoxib Superior to Celecoxib Gastrointestinal safety Inferior to Traditional NSAID Similar with Celecoxib Superior to traditional NSAIDs Similar with Celecoxib CV side effects Moderate or high High Moderate None observed to date

12. Indications For management of pain in osteoarthritis Dosage Prescribing information Polmacoxib 2021.

13. Contraindications Prescribing information Polmacoxib 2021.

14. Category Advantages of Polmacoxib Efficacy •  ​ Demonstrated quicker onset of relief from the signs and symptoms of OA over Celecoxib. • Achieved superior PGA (Physicians Global Assessment) scores, than Celecoxib with statistically significance, an efficacy endpoint for measuring the physicians’ perception of patient improvement in terms of the OA signs and symptoms. Potency Most Potent NSAID Most potent coxib in terms of CA inhibition, Dose • Able to achieve therapeutic efficacy (OA) with only 2 mg/day dose, the lowest dose among all known NSAIDs (both non-selective and selective COX-2 inhibitors). Administration Frequency • Convenient once-a-day dosing regimen → The administration frequencies of most commercially available traditional NSAIDs and incrementally modified NSAID containing products for OA range between b.i.d (twice daily) through t.i.d (three times daily). Gastrointestinal Side Effects • Polmacoxib has significantly improved GI safety profile in comparison with other commercially available NSAIDs. • The GI safety profile of Polmacoxib eliminates the need for concomitant administration of GI protectant agents. Cardiovascular Side Effects •  Polmacoxib’s unique mode of action is projected to provide a meaningful enhancement of cardiovascular safety from currently available NSAID products.

15. Non selective cox Inhibitors Selective COX2 inhibitors Tissue Selective COX inhibitors Evolution in painkillers NSAIDs

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