R1 Therapeutics has started a global phase 2b clinical trial for a new medication called AP306, designed to treat high phosphate levels in patients with advanced kidney disease who are on dialysis. This is the first time this type of medication, known as a first-in-class pan phosphate transporter inhibitor, is being tested as a standalone treatment for this condition. The trial is a multi-center study, meaning it will take place at several locations, and it will compare AP306 to a placebo (an inactive substance) to evaluate its safety, how well patients tolerate it, and its effectiveness in lowering phosphate levels over eight weeks. During this period, six different fixed doses of AP306 will be tested. The study plans to enroll around 168 patients in the United States and China, in collaboration with Alebund Pharmaceuticals.
High phosphate levels, a condition called hyperphosphatemia, are very common in people with advanced kidney disease. When phosphate levels are too high, it can lead to serious health problems such as heart disease, bone disorders, and even early death. Despite the use of phosphate binders—medications taken with meals to reduce phosphate absorption—more than 70% of dialysis patients in the U.S. still struggle to maintain normal phosphate levels. This issue has persisted for over 60 years, highlighting the need for new treatments.
L. Mary Smith, Co-Founder and Chief Operating Officer of R1 Therapeutics, shared her excitement about this milestone: ‘Starting the first patient in this trial marks a major step forward for our company and our partners. We created R1 to tackle a problem that hasn’t seen new solutions in decades. Patients on dialysis often have to take a large number of pills every day, yet many still can’t keep their phosphate levels under control. AP306 was developed to change that. Moving it into this phase 2b study with our partner Alebund is an important achievement, and we are dedicated to gathering the necessary data to bring AP306 to patients as soon as possible.’
AP306 works differently from existing treatments because it blocks the ‘active’ transport of phosphate in the gut by targeting three specific transporters. Most current phosphate-lowering medications, known as phosphate binders, work by binding to phosphate in the stomach or intestines to prevent its absorption. However, these have only shown modest success in keeping phosphate levels under control.
The phase 2b study follows promising results from an earlier phase 2a trial, published in Kidney International Reports, which showed that AP306 significantly reduced phosphate levels in the blood while maintaining a good safety profile. The new study is expected to conclude by early 2027, when researchers will share the top-line results.
Glenn M. Chertow, Chair of R1’s Scientific Advisory Board and a kidney disease expert, emphasized the significance of this trial: ‘Hyperphosphatemia is one of the most challenging issues we deal with in patients on long-term dialysis. It is linked to higher risks of death, heart problems, and bone fractures.’ He added, ‘AP306 targets phosphate absorption directly by blocking three active transporters in the gut, offering a unique way to lower phosphate levels. This could provide a new option that complements or even replaces phosphate binders, which have been used for many years with limited success.’
Chertow also expressed his enthusiasm for the study’s start, saying, ‘I’m excited to see this research underway and look forward to learning more about AP306’s potential to effectively lower phosphate levels across different doses.’
AP306 was originally discovered by Chugai Pharmaceutical and was later licensed to Alebund Pharmaceuticals for further development.