SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Tricida, Inc., a late-stage pharmaceutical company, announced results from its pivotal Phase 3 double-blind, randomized, placebo-controlled, multi-center Phase 3 clinical trial, TRCA-301, in 217 chronic kidney disease (CKD) patients with metabolic acidosis. TRC101 represents a first-in-class candidate for the treatment of metabolic acidosis, a common complication of CKD that can accelerate progression of kidney disease, increase the risk of muscle wasting and cause the loss of bone density.
Based on the initial topline analyses, the TRCA-301 trial met both its primary and secondary endpoints in a highly statistically significant manner (p < 0.0001 for all primary and secondary endpoints). TRC101 was well tolerated in the TRCA-301 trial. Both active (124 subjects) and placebo groups (93 subjects) had low discontinuation rates and low rates of treatment-related adverse events.
For the primary endpoint, after 12 weeks of treatment, 59.2% of subjects in the TRC101 treatment group exhibited an increase in blood bicarbonate level of at least 4 milliequivalents per liter (mEq/L) or achieved a blood bicarbonate level in the normal range of 22 to 29 mEq/L, compared with 22.5% of subjects in the placebo group (p< 0.0001). For the secondary endpoint, the mean change in blood bicarbonate from baseline to week 12, subjects in the TRC101 treatment group exhibited a mean increase in blood bicarbonate of 4.49 mEq/L, compared with 1.66 mEq/L in the placebo group (p<0.0001).
In addition, two pre-specified exploratory endpoints of the pivotal Phase 3 TRCA-301 trial assessed patient quality of life and improvement in muscle function. The first exploratory endpoint examined the effect of treatment with TRC101 on self-reported responses to the physical functioning subpart of the Kidney Disease and Quality of Life Short Form survey (KDQOL-SF survey). The second exploratory endpoint objectively measured physical function, assessed using a repeated chair stand test, involving a timed measurement of five repetitions of moving from a seated to standing position. Initial topline analyses of the results of the physical functioning KDQOL-SF survey showed a statistically significant positive difference in the TRC101-treated subjects compared with the placebo group after 12 weeks of treatment (p=0.0122) and the repeated chair stand test showed a trend toward significance in the positive difference in the TRC101-treated subjects compared with the placebo group (p=0.0630).
The overall safety profile of TRC101 observed in the trial was consistent with that expected for the general population of patients with Stage 3 to 5 CKD and with similar non-absorbed polymer drugs with a site of action in the gastrointestinal tract. The incidence of serious adverse events was low and balanced in the two treatment groups and none were assessed to be related to TRC101 by the clinical investigator, Medical Monitor or Drug Safety and Pharmacovigilance Team. There were two deaths in the study and both occurred in the placebo group. Overall treatment-related adverse events occurred in 9.7% of subjects in the placebo group and 13.7% of the TRC101-treated subjects. Treatment-related gastrointestinal adverse events that occurred in more than one subject include diarrhea, flatulence, nausea and constipation. Over 95% of the subjects in each group completed the trial.
TRCA-301 Clinical Trial Design
The TRCA-301 double-blind, randomized, placebo-controlled Phase 3 trial was conducted at 47 sites in the United States and Europe and enrolled 217 Stage 3b or 4 CKD patients with baseline blood bicarbonate levels between 12 mEq/L and 20 mEq/L. Subjects were randomized in a 4:3 ratio to receive TRC101 or placebo. The study drug dosing (TRC101 or placebo) continued for 12 weeks once daily. The primary outcome measure was change from baseline in blood bicarbonate (Time Frame: Week 12) and included comparison of TRC101 and placebo with regard to the proportions of subjects with change from baseline in blood bicarbonate ≥ 4 mEq/L or with blood bicarbonate in the normal range (22 to 29 mEq/L). Eligible subjects that completed the TRCA-301 trial were invited to participate in a 40-week safety extension trial, TRCA-301E. Of the 208 subjects who completed the TRCA-301 trial, 196 were enrolled in the TRCA-301E safety extension trial.
The principal investigator for the trial was Dr. Donald E. Wesson, MD, MBA, Professor of Medicine at Texas A&M Health Sciences Center College of Medicine in Dallas, Texas, President of the Baylor Scott & White Health and Wellness Center (BSW HWC), Senior Vice President of Baylor Scott & White Weight Management Services and a board-certified internist and nephrologist.
TRC101 represents a first-in-class candidate for the treatment of metabolic acidosis, a common complication of CKD that can result in accelerated progression of kidney disease. It is a novel, non-absorbed polymer drug that is designed to bind hydrochloric acid in the gastrointestinal tract, removing it from the body with high capacity and specificity, with the objective to treat chronic metabolic acidosis associated with CKD as measured by an increase in blood bicarbonate levels.
About CKD and Metabolic Acidosis
CKD is a serious condition characterized by the gradual loss of essential kidney functions over time. According to the Centers for Disease Control and Prevention, more than 30 million people in the United States are afflicted with CKD. The treatment of CKD adds a tremendous financial burden to the United States, with annual Medicare expenses for CKD, including end-stage renal disease, estimated to be approximately $98 billion. Metabolic acidosis is a chronic condition commonly caused by CKD. It is a serious condition in which the body has accumulated too much acid and occurs when a patient’s kidneys can no longer excrete sufficient acid or produce enough bicarbonate to balance acid production. The prevalence and severity of metabolic acidosis in people with CKD progressively rises as kidney function declines. As a chronic condition, metabolic acidosis is associated with an increased risk of CKD progression and increased risk of death. It is also associated with an increased risk of muscle wasting and loss of bone density. Metabolic acidosis poses a significant health risk to approximately three million CKD patients in the United States.
Tricida, Inc., is a late-stage pharmaceutical company focused on the development and commercialization of TRC101, a non-absorbed, orally-dosed polymer drug designed to treat metabolic acidosis in patients with chronic kidney disease. The results of the pivotal Phase 3 clinical trial reported today, along with results from a successful double-blind, randomized, placebo-controlled Phase 1/2 trial and an ongoing safety extension trial, TRCA-301E, are intended to serve as the basis for the submission of a U.S. New Drug Application (NDA) for TRC101 under the Accelerated Approval Program of the U.S. Food and Drug Administration (FDA).
Cautionary Note on Forward-Looking Statements
This press release includes forward-looking statements, including for example, the ability of our drug candidate to provide benefit to patients or to become a first-in-class drug for the treatment of metabolic acidosis and our ability to submit an NDA for TRC101 under the FDA’s Accelerated Approval Program. Forward‐looking statements involve known and unknown risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward‐looking statements. These risks and uncertainties include, among others, the cost, timing and results of clinical trials and other studies; that many drug candidates that have completed Phase 3 trials do not become approved drugs on a timely or cost effective basis or at all; there can be no assurance that the FDA would approve an NDA under the Accelerated Approval Program and even if approval for a drug is obtained, there can be no assurance that it will be adopted in the market or accepted as a benefit to patients and healthcare providers; and possible safety and efficacy concerns. The forward-looking statements contained in this press release reflect Tricida’s current views with respect to future events, and Tricida does not undertake and specifically disclaims any obligation to update any forward-looking statements.