Tricida Announces Positive Results From Long-Term Clinical Trial of TRC101 in Patients With CKD and Metabolic Acidosis
Blinded, randomized, placebo-controlled, 40-week extension trial, TRCA-301E, met its primary and all secondary endpoints, supporting the long-term safety and efficacy profile of TRC101
Patients treated with TRC101 showed a significant reduction in all-cause mortality and progression of CKD (defined as the composite of all-cause mortality, renal replacement therapy or a ≥ 50% decrease from baseline in eGFR) versus placebo within just one year in a prespecified analysis
Patients treated with TRC101 showed significant improvement from baseline in measures of physical function and physical function-related quality of life versus placebo
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Based on the initial topline data analyses, the TRCA-301E trial met its primary and all secondary endpoints. The primary endpoint of the TRCA-301E trial was the assessment of the long-term safety profile of TRC101 versus placebo. The results demonstrated that fewer subjects on TRC101 than on placebo discontinued the 40-week treatment period prematurely (2.6% versus 9.8%, respectively). The incidence of serious adverse events was 1.8% for subjects in the TRC101 group and 4.9% for subjects in the placebo group, and none were assessed to be related to study drug by the trial investigator, Medical Monitor or Drug Safety and Pharmacovigilance Team. The only adverse event with a between-group frequency difference of >5% was headache, which was more common in the placebo group. Gastrointestinal adverse events occurred in 21.4% of subjects in the TRC101 group and in 25.9% of subjects in the placebo group.
The statistical analysis plan for the TRCA-301E trial also specified a comparison of the TRC101 and placebo groups for the time to the composite clinical endpoint of death (all-cause mortality), dialysis/kidney transplant (renal replacement therapy) or a ≥50% decline in estimated glomerular filtration rate (eGFR) (taken together, DD50) over the combined (TRCA-301 and TRCA-301E) 52-week treatment period. Of the 124 subjects randomized to the TRC101 group, 5 (4.0%) subjects had a DD50 event. There were no deaths in the TRC101 group and one TRC101-treated subject initiated dialysis during the 52-week treatment period. Of the 93 subjects randomized to the placebo group, 10 (10.8%) subjects had a DD50 event, including four subjects who died and one who initiated dialysis during the 52-week treatment period. The time to DD50 was prolonged in the TRC101 group compared to the placebo group, with an annualized DD50 incidence rate, calculated as 100 times the number of events divided by the total person-years, of 4.2% in the TRC101 group vs 12.0% in the placebo group (p = 0.0224).
The secondary endpoints of the TRCA-301E trial assessed the durability of effect of TRC101, both on blood bicarbonate levels and on measures of physical function, over the 52-week treatment period for those subjects who participated in the TRCA-301E trial. All were met with high statistical significance.
The durability of effect of TRC101 was assessed by comparing the changes in blood bicarbonate from baseline to Week 52 between TRC101 versus placebo subjects who completed the 52-week treatment period. Sixty-three percent of the 111 TRC101 subjects treated for 52 weeks 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 38% of the 74 placebo subjects who completed 52 weeks of treatment (p=0.0015). The least squares (LS) mean change in blood bicarbonate from baseline to end of treatment in the TRC101 group was 4.7 mEq/L, compared with 2.7 mEq/L in the placebo group (p=0.0002). We believe these results support the long-term durability of blood bicarbonate effect of the TRC101-treated group compared to placebo.
Measures of physical function were assessed through the self-reported
responses to the physical functioning subpart of the Kidney Disease and
Quality of Life Short Form survey (
“This trial provides evidence of long-term safety and tolerability of
TRC101 and that the sustained increase in blood bicarbonate led to
improvements in multiple clinical outcomes that matter to both patients
and physicians,” said
The TRCA-301/TRCA-301E clinical trials were not designed or powered to assess all-cause mortality and/or the progression of CKD outcomes; they enrolled only 217 subjects and followed them over a one-year treatment period to support the long-term safety and efficacy profile of TRC101. Nevertheless, we observed a 65% reduction in the annualized event rate of the composite endpoint of all-cause mortality and/or the progression of CKD (DD50) in TRC101-treated subjects versus subjects in the placebo group.
“The 52-week TRCA-301/301E results far exceeded our expectations,” said
Today’s Conference Call and Webcast
Tricida TRCA-301E Clinical Trial Results and
Thursday, March 28, 2019
A replay of the webcast will be available on Tricida’s website approximately two hours following the completion of the call and will be available for up to 90 days.
For more information about
Cautionary Note on Forward-Looking Statements
This press release includes forward-looking statements, including for
example, statements about 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
timing of Tricida’s NDA submission; 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
Jackie Cossmon, IRC
Vice President of Investor Relations and Communications