Phathom Pharmaceuticals is developing vonoprazan, a potassium-competitive acid blocker (P-CAB). P-CABs are a new class of medicines that block acid secretion in the stomach, and we plan to evaluate vonoprazan in the treatment of patients with gastroesophageal reflux disease (GERD), H. pylori infection, and other acid-related diseases.
Gastric acid is secreted by the hydrogen potassium ATPase (also known as the proton pump). While proton pump inhibitors (PPIs) are the current standard of care for acid-related diseases, they have limitations that result in a large unmet medical need. In GERD, PPI therapy is suboptimal for many patients due to the slow onset and insufficient duration of acid control which can lead to inadequate symptom relief. Approximately 15% to 45% of GERD patients remain inadequately treated with PPIs. In the treatment of H. pylori infection, the standard of care consists of a combination of a PPI and at least two oral antibiotics. However, increasing antibiotic resistance has resulted in declining eradication rates with PPI-based therapy. We believe these unmet medical needs are in part driven by limitations associated with the mechanism of action and pharmacokinetics of PPIs.
Vonoprazan, a P-CAB, has a differentiated mechanism of action and pharmacologic profile.
- Does not require activation by gastric acid
- Is stable in the presence of acid
- Binds with a slow dissociation rate to both active and inactive proton pumps
- Has a long plasma half-life
Vonoprazan’s characteristics allow for more rapid and potent acid suppression versus the PPI esomeprazole in human subjects two hours after oral dosing and maintain target acid inhibition over a 24-hour period.
Vonoprazan was developed in markets outside of the United States through an extensive clinical program, including 17 Phase 3 clinical trials, and is approved in Japan for indications including healing and maintenance of healing of erosive esophagitis, adjunct to antibiotics in H. pylori treatment, gastric ulcer, duodenal ulcer, prevention of recurrence of gastric ulcer or duodenal ulcer during low-dose aspirin or NSAID administration. Phathom has development and commercialization rights to vonoprazan in the United States, Europe and Canada, and intends to seek approval in these geographies. We have received qualified infectious disease product (QIDP) designation from the FDA for vonoprazan in combination with certain antibiotics for the treatment of H. pylori infection which provides, among other benefits, potential eligibility for priority review and extension of any regulatory exclusivity awarded if approved.
Gastroesophageal Reflux Disease (GERD)
GERD results from the effects of acid on compromised mucosal defenses in the gastrointestinal tract. The reflux of gastric acid into the esophagus produces frequent and/or severe heartburn, indigestion, and reflux symptoms. Chronic GERD may damage esophageal tissue and progress to more severe diseases. GERD is one of the most prevalent diseases of any kind and is the most prevalent GI disease, affecting approximately 20% of the U.S. population and approximately 15% of the European population.
Approximately 15% to 45% of GERD patients are inadequately treated with PPIs, experiencing persistent, troublesome symptoms, such as heartburn and regurgitation. In approximately two thirds of symptomatic GERD patients, reflux symptoms are not adequately controlled after the first dose of a PPI, and nearly 50% of patients still suffer from symptoms three days later.
Erosive esophagitis is a condition characterized by the presence of breaks, or erosions, in the esophageal tissue caused by constant irritation of the mucosal surface and subsequent loss of defense mechanisms against acid and digestive enzymes. Chronic erosive esophagitis can lead to complications including peptic stricture, a narrowing of the esophagus that causes difficulty swallowing, and Barrett’s esophagus, a condition in which esophageal tissue changes can progress to cancer.
Helicobacter pylori (H. pylori) Infection
H. pylori is a bacterial pathogen that infects approximately 35% of the U.S. population and 45% of the population in the five major countries in the European Union (France, Germany, Italy, Spain, and the United Kingdom). As a result of the chronic inflammation induced by H. pylori infection, approximately 20% of infected patients develop a range of pathologies including dyspepsia, peptic ulcer disease, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Gastric cancer is the third most common cause of cancer-related death worldwide, and over 80% of gastric cancers are attributed to H. pylori infection. Treatment of H. pylori infection has been proven to reduce the incidence of gastric cancer, and the American College of Gastroenterologists (ACG) guidelines recommend treatment for all patients diagnosed with H. pylori infection, typically using PPIs in conjunction with antibiotics. Anti-secretory agents reduce gastric acid level, thereby increasing antibiotic stability and potency against H. pylori.
H. pylori eradication rates have fallen from >90% in the 1990s to current rates of <80% due to increasing antibiotic resistance. In 2017, the World Health Organization (WHO) listed H. pylori among the 16 antibiotic-resistant bacteria that pose the greatest threat to human health and designated H. pylori as a Class 1 carcinogen, meaning that it is a definite known cause of cancer. In 2014, the FDA added H. pylori to the agency’s list of qualifying pathogens that have the potential to pose a serious threat to public health under the Generating Antibiotic Incentives Now (GAIN) Act.
Expanded Access Policy:
At Phathom, we work every day to improve the lives of people impacted by gastrointestinal diseases and to make therapies available to patients as quickly and safely as possible. Expanded access, also referred to as compassionate use, is a channel through which the US Food and Drug Administration (FDA) allows patients to receive investigational medicines in certain circumstances outside of the context of a clinical trial.
We do not currently make any of our investigational products available through expanded access programs, as we believe that our clinical trials are the most appropriate way to access our investigational products. We encourage patients who are interested in accessing therapies in our pipeline to talk to their doctor about participating in a clinical trial. Information about all of our trials, including eligibility criteria and locations, is available at ClinicalTrials.gov.
To the extent we determine that expanded access to any of our investigational therapies becomes appropriate in the future, this website and policy will be updated to include information regarding the criteria to be used to evaluate these requests, among other information. If you have further questions, please email firstname.lastname@example.org. We anticipate that your inquiry will be acknowledged within 5 business days.