Carnot Laboratorios

Carlos Alberto Reyes M

Gastrointestinal Health Authority

Esophagitis, gastritis, and gastro-duodenal ulcers are pathologies that impact a high proportion of the population, significantly affecting patients’ quality of life. Of these, non-erosive esophagitis is the most prevalent and represents a diagnosis challenge for physicians. If, when performing the upper endoscopy, the specialist does not find macroscopic erosion or histological inflammation, pHmetry, and esophageal impedance studies should be carried out. The first one records pH levels and time of acid exposure in the esophageal mucosa and the second one identifies potentially harmful non-acid regurgitation. Early diagnosis and adequate treatment of this pathology prevent progression to erosive esophagitis, Barrett's esophagus, and esophageal cancer, in addition to improving patients’ quality of life.

Since the ´90s, the gold standard treatment for these acid-related diseases has been proton pump inhibitors (PPIs). The parietal cells of the gastric mucosa contain these energy-dependent pumps that excrete hydrogen (acid) into the lumen of the stomach, exchanging them for a potassium ion (K⁺). Doctors indicate this treatment for a month and call the patient for control, describing that 20 to 40 percent of them do not respond satisfactorily to the therapy (Fass R 2005). Most patients report feeling better but 85 percent describe symptoms persistence, even while receiving medication (Chey W 2009). This entails a high cost for the family and health payers because the doctors are forced to carry out other paraclinical studies to decline diverse causes of the symptoms.

The main reasons for the persistence of symptoms despite being esophagitis associated with gastric acid are that PPIs are administered as pro-drugs (they must be metabolized to achieve their therapeutic effect), and they have a late onset of action and short half-life time. They need to be administered on fasting, require food intake (400Kcal) 45 minutes later and only act on active proton pumps by binding them irreversibly. Carnot Laboratorios keeping its mission of ensuring that the population lives longer, fuller and happier lives through innovation in quality products and services for health, maintaining, in addition, leadership in Gastroenterology, launched Ki-CAB® (Tegoprazan developed by HK ínno. N) in Mexico, the first potassium competitive acid blocker (P-CAB), which solves the unmet needs of PPIs, since it is a drug that does not require activation, can be administered on an empty stomach or with food, initiates symptom control 30 minutes after ingestion, and it binds reversibly to the potassium binding site in the H⁺/K⁺ ATPase pump, so when new active pumps appear, Ki-CAB could block them, maintaining its effectiveness for 24 hours (Mermelstein J 2020). The Mexico PPIs market is bigger than 30 million units per year, only in the private segment, implying a disbursement of 250 million dollars (out of pocket), with a CAGR of +9 percent.

Translational medicine shows us that it took about 25 years from the discovery of a new mechanism of action to its application in clinical practice. Computerized mathematical models can currently predict the benefits of a new molecule and its therapeutic success, based on its chemical structure and historical pharmaceutics background. Carnot Laboratorios IT team also developed an application for the patient to record their symptoms related to esophageal disease in real-time, in addition, to answering internationally validated surveys, in our language and culture, to record therapeutic failure or significant clinical response within a week of starting treatment with Ki-CAB®, with the benefits it implies to confirm the specialist's diagnosis, savings in unnecessary paraclinical examinations and improvement of patient's quality of life.

Infection by the bacterium Helicobacter pylori is a gastric pathology that affects more than half of the world’s population, complicating it with mucosal ulcers in millions of patients and with stomach cancer in at least 600,000 individuals (Hooi 2017). Although its prevalence has decreased in regions with optimal hygienic conditions, its treatment has been complicated due to antibiotic resistance. In addition, this bacterium in the acidic environment of the stomach remains silent, evading the immune response and the bactericidal action of antibiotics, therefore a vital element of the treatment is to alkalinize the pH of the stomach above 6. Ki-CAB® 50 mg twice a day has been shown to achieve these levels of stomach acidity, making it the ideal adjuvant to antibiotic treatment for Helicobacter p. eradication. Currently, we can predict the sensitivity or resistance to the antibiotic before indicating it, through molecular examinations in the histological tissue of biopsies that identified the bacteria, thus significantly increasing the treatment success (Graham 2021).