Webcast today at 8:00 am Eastern
Time
Tricida, Inc. (NASDAQ: TCDA) announced today the top-line
results from its VALOR-CKD renal outcomes clinical trial, designed
to evaluate veverimer’s ability to slow CKD progression in patients
with metabolic acidosis and chronic kidney disease (CKD).
Primary Endpoint Analysis
The VALOR-CKD trial did not meet its primary endpoint, which was
defined as the time to the first occurrence of any event in the
composite endpoint of renal death, end-stage renal disease (ESRD),
or a confirmed greater than or equal to 40% reduction in estimated
glomerular filtration rate (eGFR), also known as DD40. One hundred
forty-nine veverimer-treated patients versus 148 placebo-treated
patients experienced a DD40 primary endpoint event, representing a
veverimer to placebo hazard ratio of 0.99 [95% CI, 0.78, 1.24;
(p=0.898)] over the 26.7 months median duration of treatment.
Primary Endpoint Event
Analysis
Veverimer (N =
739)
Placebo (N =
737)
Hazard Ratio (95% CI)
p-value
Number (%) of Patients with
Primary Endpoint Event
149 (20.2%)
148 (20.1%)
0.99
0.898
Annualized Primary Endpoint Event
Rate
9.9%
9.8%
The VALOR-CKD Trial Design
The VALOR-CKD trial was an international, randomized,
multicenter, double-blind, placebo-controlled trial of patients
with CKD and metabolic acidosis. To qualify for enrollment in the
study, patients were required to have two eGFR values, taken at
least 2 weeks apart, in the range of 20 to 40 mL/min/1.73m2, that
were not more than 20% different from each other and three serum
bicarbonate values, each taken at least 2 weeks apart from the
others and all three within a 6-week period (the Screening Period),
in the range of 12 to 20 mEq/L. The entry criteria for the study
also required that patients be on a stable, maximum-tolerated,
labeled dose of an angiotensin converting enzyme (ACE) inhibitor
and/or angiotensin II receptor blocker (ARB) for at least 4 weeks
prior to and during the Screening Period. Both patients taking oral
alkali supplements and those not taking them were eligible for
enrollment; however, a patient’s use and dose of oral alkali was
not to be changed during the study and those taking oral alkali
were required to be on a stable dose for at least 2 weeks prior to
and during the Screening Period. There were no prohibited
drugs.
Eligible patients were enrolled into a single-blind
active-treatment period of 4 to 8 weeks (Part A) that was followed
by a randomized withdrawal into a double-blind, randomized
treatment period (Part B). Patients in Part A who experienced a
greater than or equal to 4 mEq/L increase from baseline in serum
bicarbonate and those whose serum bicarbonate increased into the
normal range of greater than or equal to 22 mEq/L at Week 4 were
randomized in a 1:1 ratio either to continue treatment with
veverimer or to treatment with placebo for the double-blind, Part
B, portion of the trial. Patients who did not achieve the required
serum bicarbonate response to veverimer after 4 weeks in Part A
continued to receive veverimer for an additional 4 weeks. After 8
weeks of veverimer treatment in Part A, those patients who
experienced a greater than or equal to 4 mEq/L increase in serum
bicarbonate and those whose serum bicarbonate increased into the
normal range of greater than or equal to 22 mEq/L were randomized
in a 1:1 ratio to either continued treatment with veverimer or to
treatment with placebo in Part B. Those patients who did not
achieve the desired serum bicarbonate response after 8 weeks in
Part A discontinued treatment with veverimer and exited the
study.
In total, 2,198 patients received single-blind treatment with
veverimer in Part A. Of these, 1,480 patients were randomized into
Part B. The randomized patient population had a mean baseline eGFR
of 29.2 mL/min/1.73m2 and a mean baseline serum bicarbonate of 17.5
mEq/L. The majority of patients randomized in the trial had one or
more co-morbid conditions, such as hypertension, heart failure or
diabetes. Approximately 12% of patients in the trial were taking
oral alkali at baseline. The table below provides selected
demographics and baseline characteristics of veverimer- and
placebo-treated patients.
Selected Demographics and
Baseline Characteristics
Veverimer N =
741
Placebo N = 739
Mean Age (SD) – years
65.0 (11.87)
65.2 (12.30)
Male – N (%)
433 (58.4)
421 (57.0)
Mean eGFR (SD) –
mL/min/1.73m2
29.2 (6.35)
29.1 (6.33)
Serum Bicarbonate (SD) –
mEq/L
17.4 (1.39)
17.5 (1.32)
Hypertension – N (%)
726 (98.0)
724 (98.0)
Diabetes – N (%)
423 (57.1)
399 (54.0)
Heart Failure – N (%)
230 (31.0)
241 (32.6)
Oral Alkali Use – N (%)
83 (11.2)
87 (11.8)
Serum Bicarbonate Analysis
Based on the results from the veverimer arm of the previous
TRCA-301 trial, the Part A run-in period was designed to achieve a
large separation of serum bicarbonate levels in veverimer-treated
subjects and subjects in the placebo group over the duration of
treatment. Accordingly, Tricida expected the treatment effect in
Part A would be an approximately 6 mEq/L increase in serum
bicarbonate and that 74% of subjects treated in Part A would
achieve the necessary increase in serum bicarbonate to proceed to
randomization in Part B. Based on results of both TRCA-301E and the
Phase 1/2 trial, TRCA-101, Tricida also anticipated that after
withdrawal of veverimer at the end of Part A in patients randomized
to placebo, serum bicarbonate levels would rapidly decline to near
baseline levels, while continued treatment with veverimer in those
randomized to the active arm of the trial would result in
maintenance of serum bicarbonate levels achieved in Part A.
In the VALOR-CKD trial, at the completion of Part A, 67% of
subjects achieved at least a 4 mEq/L increase in serum bicarbonate
or a serum bicarbonate increased into the normal range of greater
than or equal to 22 mEq/L and were randomized into Part B. Of the
1,480 patients randomized into Part B, the average increase from
baseline in serum bicarbonate was 5.9 mEq/L, increasing from 17.5
mEq/L to 23.4 mEq/L. After 3 months of treatment in Part B, the
average serum bicarbonate in the veverimer- and placebo-treated
groups declined to approximately 22 mEq/L and 21 mEq/L,
respectively, and these levels were maintained for the majority of
the treatment duration. Furthermore, at each of the 3-month
timepoints between Month 3 and Month 30 in Part B, approximately
60% of the patients in the placebo group had a level of serum
bicarbonate above 20 mEq/L. Thus, the difference in serum
bicarbonate levels between the two groups was insufficient to
evaluate the effect of veverimer on slowing CKD progression in
patients with metabolic acidosis and CKD.
“Unfortunately, due to the higher than expected serum
bicarbonate values in the placebo group, we were not able to
compare an untreated acidotic population with a veverimer-treated
population and were thus unable to assess veverimer’s ability to
slow CKD progression. Given our past clinical experience with
veverimer, and the VALOR-CKD trial design, we were surprised that
there was not a greater separation in serum bicarbonate levels
between the two groups,” stated Gerrit Klaerner, Ph.D., Tricida’s
Chief Executive Officer, and President. “In light of the
disappointing results from the trial, and our cash runway, we are
evaluating next steps.”
Analysis of Secondary Endpoints
Given the failure on the primary endpoint, our prespecified
hierarchical analysis did not permit statistical testing of the
secondary endpoints, however, the nominal p-values for all of these
endpoints were non-significant.
Safety Analysis
The overall safety profile of veverimer observed in both Part A
and Part B of the trial was consistent with that expected for the
general population of patients with Stage 3 to 5 CKD. The incidence
of all-cause death (14.2% vs. 14.0%) and cardiovascular death (5.7%
vs. 6.0%) was balanced between patients randomized to veverimer and
placebo. The percentage of patients reporting serious adverse
events (SAEs) (26.7% and 27.8%) was also similar in the two
respective groups. There were only 2 treatment-related SAEs.
Adverse events resulting in discontinuation of randomized study
drug treatment were reported for 6.6% of the veverimer group and
6.0% of the placebo group. The majority of adverse events were mild
to moderate in severity and balanced between the two groups. The
most common adverse events (i.e., those reported in at least 5% of
the veverimer group), in the veverimer and placebo groups,
respectively, were hypertension (8.8% vs. 9.6%), hyperkalemia (7.4%
vs. 5.8%), COVID-19 (5.3% vs. 7.3%), headache (5.3% vs. 5.0%), and
anemia (5.1% vs. 4.9%).
Today’s Conference Call and Webcast
Tricida will host a conference call and webcast that will
include a slide presentation at 8:00 am Eastern Time to discuss the
results of the VALOR-CKD clinical trial:
The VALOR-CKD Clinical Trial
Results Conference Call
Monday, October 24,
2022
8:00 am Eastern Time
Webcast:
IR.Tricida.com
Dial-in:
(800) 715-9871
International:
(646) 307-1963
Conference ID:
2832909
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 of its investigational drug candidate, veverimer, a
non-absorbed, orally-administered polymer designed to slow CKD
progression in patients with metabolic acidosis and 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 4.3 million patients with
CKD in the United States. There are currently no therapies approved
by the FDA to slow progression of kidney disease through the
treatment of chronic metabolic acidosis in patients with CKD.
For more information about Tricida, please visit
Tricida.com.
Cautionary Note on Forward-Looking Statements
This press release includes forward-looking statements within
the meaning of Section 27A of the Securities Act of 1933 and
Section 21E of the Securities Exchange Act of 1934. Forward-looking
statements relate to expectations concerning matters that are not
historical facts. Words such as “projects,” “believes,”
“anticipates,” “plans,” “expects,” “intends,” “may,” “will,”
“could,” “should,” “would,” and similar words and expressions are
intended to identify forward-looking statements. Forward-looking
statements involve risks and uncertainties that could cause actual
results to differ materially from those discussed in such
forward-looking statements. Such risks and uncertainties include,
without limitation, risks associated with the Company’s business
prospects, financial results and business operations.
These and other factors that may affect the Company’s future
business prospects, results and operations are identified and
described in more detail in the Company’s filings with the
Securities and Exchange Commission (the “SEC”), including the
Company’s most recent Annual Report filed on Form 10-K and the
subsequently filed Quarterly Report(s) on Form 10-Q. You should not
place undue reliance on these forward-looking statements, which
speak only as of the date of this press release. Except as required
by applicable law, the Company does not intend to update any of the
forward-looking statements to conform these statements to actual
results, later events or circumstances or to reflect the occurrence
of unanticipated events.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20221024005383/en/
Jackie Cossmon, IRC Tricida, Inc. Senior Vice President of
Investor Relations and Communications IR@Tricida.com
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