vonoprazan A novel drug for GERD presentation

Vonoprazan, a new potassium acid channel blocker used in the conditions of GERD and gastric ulcer, duodenal ulcer ....

1. Vonoprazan ( Novel Potassium-competitive acid blocker ) Dr. Pavithra. A Pharm.D

2. 2 Vonoprazan

3. 3 Indications

4. 4 Let’s Look Into History…..

5. 5 Key Milestones….

6. 6 Vonoprazan is a potassium-competitive acid blocker (PCAB) used in the treatment of acid-related disorders and as an adjunct to Helicobacter pylori (H. pylori) eradication. It inhibits H+, K+-ATPase-mediated gastric acid secretion, making it an alternative to proton-pump inhibitors (PPIs) for these conditions Mechanism of Action

7. 7 Vonoprazan is considered superior to other proton pump inhibitors (PPIs) Potency: Vonoprazan is 350 times more potent than lansoprazole , as it accumulates in the gastric corpus mucosa, specifically in the parietal cells, allowing for more effective acid inhibition   Rapid and Long-Lasting Effect: Vonoprazan has a rapid and long-lasting effect on gastric acid inhibition, which is not affected by the acid secretory state, mealtime, or CYP2C19 polymorphism . This makes it a more effective option for acid-related disorders .

8. 8 A re there any specific patient demographics that benefit more from vonoprazan Severe Erosive Esophagitis : Vonoprazan is superior to lansoprazole in healing and maintaining healing of severe erosive esophagitis, especially in LA Grade C/D cases. High-Risk Conditions : Vonoprazan may be more effective for high-risk patients, including extensive metabolizers of PPIs, due to its lack of dependence on CYP2C19 polymorphism. Hypergastrinemia : Vonoprazan has a lower risk of hypergastrinemia compared to lansoprazole, beneficial for patients with this condition. Acid-Resistant Ulcers : Vonoprazan’s rapid and effective inhibition of gastric acid secretion makes it a better choice for acid-resistant ulcers, such as those from endoscopic submucosal dissection (ESD).

9. 6/11/2024 Name 9 Vonoprazan: will it modify the mainstay? In1996, when Cimetidine (Tagamet by SKF) got approval, physicians got something magical to treat gastric acid related diseases . This first-in-class H2-blocker became the first blockbuster drug- i.e., ever to reach more than $1 billion a year in sales. Not only that, its successor Ranitidine (Zantac by GSK) became the world's biggest-selling prescription drug by 1988- only within seven years of approval (1981).

10. 6/11/2024 Name 10 Then in 1989, a game-changer, Omeprazole ( Prilosec / Losec by AstraZeneca) jumped in the competition. It was the first PPI (Proton Pump Inhibitor) that got approval followed by five more within 2015 Undoubtedly, those six molecules won the battle with the H2-blockers

11. 6/11/2024 Name 11 In 2015 a new class viz. Potassium competitive acid blockers (PCAB) came into play. Vonoprazan ( Takecab by Takeda) got approval in Japan.

12. 6/11/2024 Name 12 Efficiency of a gastric acid-suppressant depends on the following two factors:

13. 6/11/2024 Name 13 These two vital factors are reflected by the Pka value of the molecules . It can be noticed in graph , where the rabeprazole has the highest Pka value (4.5) among PPIs. That why rabeprazole can be taken only 5 minutes before meal while other PPIs need at least 30 minutes for rendering the best acid suppressing effect.

14. 6/11/2024 Name 14 Vonoprazan has a pKa value of 9.1 which is much higher than lansoprazole (pKa = 3.8) The higher pKa value of vonoprazan indicates that it can be easily protonated and accumulated at high concentrations in the acidic environment of the stomach This allows Vonoprazan to inhibit gastric acid secretion more effectively than other PPIs The high pKa value of vonoprazan makes it a potent potassium-competitive acid blocker (P-CAB) that can effectively suppress gastric acid production Pharmacokinetic profile make it a promising alternative for managing acid-related diseases.

15. 6/11/2024 Name 15 W hich countries have the highest demand for Vonoprazan?

16. 6/11/2024 Name 16 W hich countries have the highest demand for Vonoprazan?

17. 6/11/2024 Name 17 The sales of vonoprazan are high in several regions and countries, particularly in Asia Pacific and the United States. Here are some key points indicating high sales: Asia Pacific: Vonoprazan is widely used in Japan, where it was first marketed in 2015 for the treatment of acid-related disorders and as an adjunct to Helicobacter pylori eradication. United States: Phathom Pharmaceuticals has received FDA approval for vonoprazan in a co-packaged product with amoxicillin and clarithromycin for the treatment of Helicobacter pylori infection, which has contributed to its sales in the region. India: Torrent Pharma has signed a non-exclusive patent licensing pact with Takeda to commercialize vonoprazan under the brand name Kabvie, which will make it accessible to the Indian population and contribute to its sales in the region

18. 6/11/2024 Name 18