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

Webcast Today at 8:00 am ET

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Tricida, Inc. (NASDAQ: TCDA), a pharmaceutical company focused on the
development and commercialization of its drug candidate, TRC101
(veverimer), a non-absorbed, orally-administered polymer designed to
treat metabolic acidosis in patients with chronic kidney disease (CKD),
announced today results from its blinded, randomized,
placebo-controlled, multicenter clinical trial, TRCA-301E, in 196 CKD
patients with metabolic acidosis. TRC101 represents a first-in-class
drug candidate for the treatment of metabolic acidosis, a chronic
condition commonly caused by CKD that is believed to accelerate the
progression of CKD, increase the risk of muscle wasting and cause the
loss of bone density. The TRCA-301E trial was a 40-week extension of the
12-week TRCA-301 trial, which randomized 217 patients with non-dialysis
dependent CKD and metabolic acidosis to treatment with TRC101 (N=124) or
placebo (N=93). Two hundred eight (208; 95.9%) subjects completed the
12-week treatment period in the TRCA-301 trial and had the option to
continue into the extension trial and receive the same blinded treatment
(TRC101 or placebo) to which they were assigned in the parent trial. One
hundred ninety-six subjects (196; 94.2%), (114 in the TRC101 group and
82 in the placebo group) elected and were qualified to continue in the
extension trial. One hundred eleven (111; 97.4%) subjects in the TRC101
group and 74 (90.2%) subjects in placebo group completed one year of
treatment. Results from the TRCA-301 and TRCA-301E trials will support
the TRC101 New Drug Application (NDA) submission planned for the second
half of 2019.

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 (KDQOL Physical Functioning Survey)
and a repeated chair stand test. Improvement from baseline to end of
treatment in the self-reported responses to the KDQOL Physical
Functioning Survey was significantly greater in the TRC101 group (+11.4
points) compared to the placebo group (-0.7 points), with a
between-group difference of 12.1 points in favor of TRC101 (p<0.0001).
Improvement from baseline to end of treatment in physical function using
a repeated chair stand test, which involved a timed measurement of five
repetitions of moving from a seated to standing position, was also
significantly greater in the TRC101 group (4.3 seconds faster) compared
to the placebo group (1.4 seconds faster), with a between-group
difference of 2.9 seconds in favor of TRC101 (p<0.0001). The
placebo-adjusted improvements in favor of TRC101-treated subjects in the
two measures of physical function at Week 52 approximately doubled
compared to the results at Week 12 observed in the parent trial,
TRCA-301. We believe the results from the KDQOL Physical Functioning
Survey and the repeated chair stand test provide consistent evidence of
a clinically meaningful improvement in physical function and related
aspects of quality of life for TRC101-treated subjects.

“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 Donald E. Wesson, M.D., M.B.A., Professor of
Medicine at Texas A&M Health Sciences Center College of Medicine in
Dallas, TX, and the lead investigator for the trial. “Furthermore, the
outcomes observed in the placebo arm of this well-controlled,
multi-center trial reiterate the importance to diagnose and treat
metabolic acidosis in patients with CKD.”

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
Gerrit Klaerner, Chief Executive Officer and President of Tricida. “We
did not anticipate that we would observe evidence of clinical benefit
beyond the increase in blood bicarbonate in patients treated with TRC101
until the read out of the results of our postmarketing trial, VALOR-CKD,
in the 2022 to 2023 timeframe. We remain committed to submitting our NDA
under the Accelerated Approval Program in the second half of 2019 and
look forward to the results of our VALOR-CKD confirmatory postmarketing
trial.”

Today’s Conference Call and Webcast

Tricida will host a conference call and webcast at 8:00 am Eastern Time
to discuss its TRCA-301E results, fourth quarter and full year 2018
financial results and other business progress. The call or webcast may
be accessed as follows:

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.

About Tricida

Tricida, Inc. is a pharmaceutical company focused on the development and
commercialization of its drug candidate, TRC101, a non-absorbed,
orally-administered polymer designed to treat metabolic acidosis in
patients with CKD. Metabolic acidosis is a condition commonly caused by
CKD that is believed to accelerate the progression of kidney
deterioration. It is estimated to pose a health risk to approximately
three million patients with CKD in the United States. Tricida has
successfully completed all of the clinical trials that it planned to
complete prior to submission of an NDA to the U.S. Food and Drug
Administration (FDA). Tricida plans to submit an NDA, in the second half
of 2019, seeking approval of TRC101 through the FDA’s Accelerated
Approval Program.

For more information about Tricida, please visit www.Tricida.com.

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 FDA
will find that our clinical trials have provided evidence of clinical
benefit; there can be no assurance that the FDA would approve an NDA
under the Accelerated Approval Program, or at all, 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; possible safety and efficacy concerns; and that we
completely rely on third-party suppliers to manufacture TRC101. 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.

Contacts

Jackie Cossmon, IRC
Tricida, Inc.
Vice President of Investor
Relations and Communications
[email protected]