Fexuprazan taking over K-CAB market? Study unveiled

Analyzing competitiveness of fexuprazan, a next-generation GERD treatment, against PPI

As Daewoong Pharmaceutical unveiled Phase III clinical data of its next-generation gastroesophageal reflux disease agent in development, fexuprazan, the Korean pharmaceutical industry is keeping a close eye on the prospective competition between the existing proton pump inhibitors (PPI) tegoprazan (Brand name: K-CAB) and the novel agent.

 

Reversibly blocking the proton pump, a potassium-competitive acid blocker’s (P-CAB) efficacy compared to PPI has been confirmed through the clinical trial conducted in Korea, but the market competition would heavily rely on pricing, indication and improved efficacy.

 

▲Improved efficacy against PPI esomeprazole confirmed On May 2, the Korean pharmaceutical company presented the Phase III clinical data of fexuprazan at Digestive Disease Week (DDW) 2020 as an e-Poster.

 

Daewoong Pharmaceutical’s novel agent treating gastroesophageal reflux disease (GERD), fexuprazan is a P-CAB that reversibly blocks the proton pump secreting gastric acid from the stomach walls.

 

Clinical trial result on heartburn relief

Frequently, a PPI is prescribed to treat patients with GERD, but its limitations like slow acting time, varying effects depending on prior food intake and individual CYP2C19 genotype, and drug-drug interaction have been reported.

 

Whereas P-CAB agent is considered a new generation of medicine that covers most of the limitations PPI faces.

 

The Phase III clinical trial was conducted in patients with erosive esophagitis at 25 hospitals in Korea, and it compared efficacy in 40 mg of PPI esomeprazole (n=111) and 40 mg of P-CAB fexuprazan (n=107).

 

Until week 4, fexuprazan and esomeprazole respectively demonstrated endoscopic mucosal healing rate at 90.3 percent and 88.5 percent, but they reached 99.1 percent at week 8.

 

Specifically, P-CAB showed comparatively faster and better heartburn relief.

 

30.8 percent of fexuprazan group and 23.4 percent of esomeprazole group had their day and nighttime symptoms relieved at day 3.

 

Comparing only patients with moderate to severe symptoms, 22.4 percent of fexuprazan group experienced symptom relief, whereas only 7.9 percent of esomeprazole group did.

 

At day 7, the heartburn symptom relief rates were recorded at 26.2 percent and 21.6 percent in fexuprazan and esomeprazole users, respectively.

 

Comparing again the patients with moderate to severe symptoms, fexuprazan demonstrated better rate at 13.8 percent against 7.9 percent.

 

The results were similar when comparing symptom relief during nighttime.

 

Reportedly, PPI was unable to maintain the effect during nighttime.

 

The nighttime heartburn relief rate of fexuprazan and esomeprazole at day 3 each marked 41.1 percent and 35.1 percent, but in patients with moderate to severe symptoms, the rate was at 34.5 percent and 17.5 percent, respectively.

 

The atypical symptom relief rates in patients with GERD were at 81.2 percent and 68.6 percent in fexuprazan and esomeprazole users, respectively, at Day 3.

 

And the rate remained around the same at week 8 at 80.6 percent and 69.3 percent, respectively.

 

Adverse reactions reported from both groups were about the same.

 

In the future, the novel agent would be inevitably compared to the ‘Old Drug,’ esomeprazole.

 

▲Competitive against the market-dominating tegoprazan?

 

In 2018, CJ Healthcare has received the government’s approval on the 30th Korean-made novel P-CAB agent ‘K-CAB (tegoprazan).’ In Japan, vonoprazan is released in the market, but K-CAB is the only P-CAB available in the Korean market.

 

As a follow-on drug, fexuprazan would attempt to take over the market from tegoprazan, unavoidably.

 

In last March, tegoprazan has been indicated to treat helicobacter pylori infection and also it has ongoing clinical trials regarding maintenance therapy after treating GERD and preventive therapy against nonsteroidal anti-inflammatory drug-induced duodenal ulcer to expand indications.

 

Fexuprazan would have to face tegoprazan, currently dominating the market not only with its effect, but as a first-in-class and its variety of indications.

 

Then, how about the differences in their efficacy?

 

In March last year, a SCI-level medical journal Alimentary Pharmacology & Therapeutics (AP&T) published Phase III clinical data of tegoprazan.

 

Same with fexuprazan, the study compared tegoprazan’s efficacy and safety in patients with erosive esophagitis against esomeprazole’s.

 

The eight-week multicenter Phase III trial on tegoprazan conducted in Korea tested 302 patients with erosive esophagitis by administering 50 mg (n=100) and 100 mg (n=102) of tegoprazan and 40 mg (n=100) of esomeprazole.

 

At week 8, the mucosal healing rate of three patient groups all reached 98.9 percent.

 

As for fexuprazane, the rate was at 99.1 percent.

 

The heartburn rate in tegoprazan 50 mg group started from 1.76 and was increased to 0.53 and 0.56 at week 4 and week 8, and in 100 mg group the rate fell from 1.86 to 0.62 and 0.62 at the same period.

 

The rate in esomeprazole group was dropped from 1.84 to 0.48 and 0.47 at week 4 and week 8.

 

The prevalence of adverse reaction in 50 mg and 100 mg of tegoprazan users reached 28.3 percent and 23.5 percent, respectively.

 

The rate was similar in 40 mg of esomeprazole users with 30.3 percent.

 

Professor Kim Gwang Ha of Pusan National University Department of Internal Medicine, who participated in both tegoprazan and fexuprazan studies, explained “The clinical trial on fexuprazan confirmed significantly improved efficacy in the novel agent against esomeprazole with patients having moderate to severe symptoms,” and “when it gets released in the market, it could be more expensive than PPIs but the benefit could outweigh the high pricing.” He added, “Based on the acting time and effect of inhibiting proton pump faster and better than PPI demonstrated in the clinical trial, the novel agent would fulfill the medical unmet needs the existing PPIs lacked,” and “patients who failed to relieve the symptoms with PPI would benefit from P-CAB.” “However, the healthcare providers should be aware that not all P-CABs have same effect and safety profile,” so “their marketability and competitiveness should be more accurately assessed with further head-to-head studies between different P-CABs,” the professor noted.