UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): October 1, 2014
ARDELYX, INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-36485 | 26-1303944 | ||
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification Number) |
34175 Ardenwood Blvd.
Fremont, CA 94555
(Address of principal executive offices, including Zip Code)
Registrant’s telephone number, including area code: (510) 745-1700
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
| Item 7.01 | Regulation FD Disclosure. |
On October 1, 2014, Ardelyx, Inc. (the “Company”) issued a press release reporting results from its Phase 2b clinical trial evaluating tenapanor in patients with constipation-predominant irritable bowel syndrome (“IBS-C”).
The Company will host an investor conference call and webcast at 8:00 a.m. ET on Wednesday, October 1, 2014 to discuss the Phase 2b results. The live webcast and a replay may be accessed by visiting the Company’s website at http://ir.ardelyx.com/.
Conference call information is as follows: (855) 296-9612 (U.S.) or (920) 663-6277 (international). Conference ID number is 13895374.
Representatives of the Company intend to present the information in the slides attached hereto as Exhibit 99.1, which is being furnished herewith under this Item 7.01.
The information furnished under this Item 7.01 shall not be considered “filed” under the Securities Exchange Act of 1934, as amended, nor shall it be incorporated by reference into any future filing under the Securities Act of 1933, as amended, or under the Securities Exchange Act of 1934, as amended, unless the Company expressly sets forth in such future filing that such information is to be considered “filed” or incorporated by reference therein.
| Item 8.01 | Other Events. |
On October 1, 2014, the Company announced positive results from its Phase 2b clinical trial evaluating tenapanor, a minimally-absorbed inhibitor of the intestinal sodium transporter NHE3, in patients with IBS-C. Results from this study demonstrated statistically significant and clinically meaningful improvement in IBS-C symptoms for tenapanor-treated patients compared to patients receiving placebo. At the 50 mg dose, the study met its primary efficacy endpoint of an increase in the complete spontaneous bowel movement (“CSBM”) responder rate.
The clinical trial was a Phase 2b, randomized, double blind, placebo-controlled, multi-center study to evaluate the safety and efficacy of three dose levels of tenapanor in 371 subjects with IBS-C as defined by the Rome III criteria and who had active disease as determined during a two-week screening period. Subjects who qualified and who were randomized into the study received 5, 20, or 50 mg of tenapanor or placebo twice daily for 12 consecutive weeks. At the end of this treatment period, subjects were followed for an additional 4 weeks. The primary endpoint, overall CSBM responder rate, was achieved in 60.7 percent of patients receiving tenapanor 50 mg twice daily versus 33.7 percent receiving placebo (p<0.001). A responder was defined as a patient who had an increase of greater than or equal to one CSBM from baseline during 6 out of 12 weeks. The results are reported on an intent-to-treat basis.
The overall responder rate, or dual composite endpoint percent, was achieved in 50 percent of patients receiving tenapanor 50 mg twice daily versus 23.6 percent receiving placebo (p<0.001). An overall responder was defined as a patient who was an overall CSBM responder and who experienced at least a 30 percent decrease in abdominal pain from baseline in the same week for 6 of 12 weeks. In addition, of those patients who were administered 50 mg twice daily, over 65 percent responded that they were ‘quite satisfied’ or ‘very satisfied’ with tenapanor versus about 38 percent with placebo, a result that was statistically significant.
Most secondary endpoints measured also demonstrated significant improvements for patients receiving 50 mg tenapanor twice daily compared to placebo-treated patients. A dose response relationship among all doses was observed in the primary endpoint, as well as in most secondary endpoints, although statistical significance was not achieved at the 5 mg or 20 mg doses. Additionally, the activity of tenapanor was maintained throughout the entire 12-week treatment period.
Tenapanor was well-tolerated in these patients, and the safety results were consistent with those observed in previous tenapanor trials. The most common adverse events at 50 mg twice daily (greater than or equal to 5 percent) that occurred more frequently in tenapanor-treated patients compared to placebo-treated patients were diarrhea at 11.2 percent vs. 0 percent, and urinary tract infections at 5.6 percent vs. 4.4 percent. Overall rates of discontinuation due to adverse events were 4.5 percent for the tenapanor-treated patients (50 mg twice daily) and 3.3 percent for the placebo-treated patients. Based on the analysis of plasma samples tested as part of the study, the minimally systemic nature of tenapanor was confirmed. The findings of the clinical study are expected to be presented in an appropriate peer-reviewed forum.
| Item 9.01 | Financial Statements and Exhibits. |
| (d) | Exhibits. |
| Exhibit No. |
Description | |
| 99.1 | Corporate presentation of Ardelyx, Inc. | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: October 1, 2014 | ARDELYX, INC. | |||||
| By: | /s/ Mark Kaufmann | |||||
| Mark Kaufmann | ||||||
| Chief Financial Officer | ||||||
EXHIBIT INDEX
| Exhibit No. |
Description | |
| 99.1 | Corporate presentation of Ardelyx, Inc. | |
 IBS-C
Phase 2b Results October 2014
Exhibit 99.1 |
 2
Tenapanor Reduces Sodium and
Phosphorus Absorption
Dietary Sodium/Phosphorus Passes
Into Circulation
Diverts Sodium/Phosphorus
from Circulation
WITHOUT TENAPANOR
WITH TENAPANOR
Tenapanor is a non-systemic small
molecule inhibitor of NHE3, a sodium
transporter present on the epithelia of
the GI tract
Tenapanor
Sodium
Phosphorus
Local Activity
in the Gut
Sodium
Phosphorus |
 3
Phase 2b Design for Tenapanor in IBS-C
•
Design:
Double-blind, placebo-controlled, randomized
1:1:1:1 into three treatment arms, 1 placebo arm
(approximately 93 patients/group) for a total of 371
patients;
12
weeks
treatment,
4
weeks
follow-up
•
Primary Endpoint:
Percent complete spontaneous bowel
movement (CSBM)*
responders (patient needs to have an
increase of at least one CSBM from baseline for 6 of the
12 treatment weeks)
•
Secondary Endpoints:
•
Treatment Arms:
IBS-C Phase 2b Protocol
RANDOMIZATION
*CSBM
defined
as
a
bowel
movement
that
feels
complete
and
is
not
aided
by
the
use
of
any
other
medication,
like
a
laxative
PLACEBO
BID
TENAPANOR 5 MG BID
TENAPANOR 20 MG BID
TENAPANOR 50 MG BID
Overall
Responder
Rate,
Abdominal
Pain and Abdominal and IBS-C Symptoms |
 4
Tenapanor in IBS-C Phase 2b Results: Efficacy
•
Trial met primary efficacy endpoint: complete spontaneous bowel movement
(CSBM) responder [60.7% in tenapanor 50 mg bid group vs. 33.7% placebo;
p<0.001]
•
The
overall
responder
rate
for
the
dual
composite
endpoint
(CSBM
responder
and
abdominal
pain
responder
in
6
of
12
weeks)
was
higher
in
the
tenapanor
50 mg bid group compared to the placebo group [50.0% vs. 23.6% placebo;
p<0.001]
•
This dual composite endpoint is the primary regulatory endpoint in Europe
and US (EMA draft guidance 2013, FDA guidance 2012) |
 5
Tenapanor in IBS-C Phase 2b Results: Efficacy (con’t)
•
Dose
response
relationship
was
observed
in
the
primary
endpoint,
as
well
as
in most other secondary endpoints, although statistical significance was not
achieved at the 5 mg or 20 mg doses; activity of tenapanor was maintained
throughout entire 12-week treatment period
•
Adequate relief of IBS symptoms was statistically significant (p=0.002) for
tenapanor 50 mg bid (63.1%) versus placebo (39.3%) at the endpoint week
(week 12 or last valid week)
•
Based
on
the
treatment
satisfaction
patient
scale
questionnaire,
more
subjects
receiving
50
mg
bid
responded
that
they
were
“quite
satisfied”
or
“very satisfied”
with tenapanor versus placebo [65% vs. 38% placebo;
p<0.001] |
 6
Tenapanor in IBS-C Phase 2b Results: Safety
•
Tenapanor well-tolerated across all treatment arms, and there were no
serious drug-related adverse events.
•
The
most
common
adverse
events
at
50
mg
bid
(
5%)
that
occurred
more
frequently in tenapanor-treated patients compared to placebo-treated
patients were diarrhea 11.2 percent vs. 0 percent and urinary tract infections
5.6 percent vs. 4.4 percent
•
Based on the analysis of plasma samples tested as part of the study, the
minimally systemic nature of tenapanor was confirmed |
 7
Tenapanor for IBS-C
GI Disorder:
Constipation and
Abdominal Pain
IBS-C MARKET
•
Medical Need for Improved Therapies with Better
Efficacy, Excellent Safety and Tolerability
–
Achieve Endpoint in Only 7% to 20% of Patients
–
Side Effects (e.g., Nausea and Diarrhea,
respectively)
•
Amitiza®
and Linzess®
Fall Short:
•
OTC Drugs Inexpensive but Not Very
Effective in Moderate to Severe Cases
LIMITATIONS OF CURRENT TREATMENTS
•
Approximately 1.4% of the US population,
or 4.4 million individuals, have IBS-C.
•
About one million patients have been
diagnosed |
 8
Tenapanor Demonstrates Dose Level and Dose Frequency
Response; Stool and Urine Sodium Correlate
1
1
RDX5791-102
published
in
Spencer
et
al
Sci
Transl
Med
6,
227ra36
(2014)
*P
<
0.05
versus
placebo,
†P
<
0.05
versus
30
mg
once
daily.
Data
are
means
±
SEM.;
PHASE 1 IN HEALTHY ADULT VOLUNTEERS
-
10
20
30
40
50
Placebo
3 mg QD
10 mg QD
30 mg QD
100 mg
QD
-
10
20
30
40
50
Placebo
30mg QD
30mg BID
30mg TID |
   9
Phase 2a Had Demonstrated Activity with QD Dosing
DUAL ENDPOINT: >30% DECREASE IN WEEKLY ABDOMINAL PAIN SCORE AND >1
INCREASE IN CSBM FREQUENCY AS COMPARED TO BASELINE
*
p<0.05 versus placebo
*
severity
and
QOL
measurements
with
QD
dosing
although
the
primary
endpoint,
change
in
CSBM
from
Baseline to Week 4, was not
met in this Phase 2a study.
Percent
Responders
End of Treatment
0%
10%
20%
30%
40%
Week 1
Week 2
Week 3
Week 4
Follow-Up
Week 1
Follow-Up
Week 2
Placebo (n=47)
100mg QD (n=46)
Improvements
in
degree
of
bloating
and
abdominal
pain
were
noted,
as
well
as
relief
of
IBS
symptoms, |
 10
Tenapanor Program –
Renal Indications and IBS-C
PROGRAM
INDICATION
RESEARCH
PHASE 1
PHASE 2
STATUS
2a
2b
Tenapanor
(NHE3 Inhibitor)
ESRD-Pi (1)
Phase 2b Data
1H:2015
IBS-C (2)
Phase 2b Data
Announced
Oct 1, 2014
CKD (3)
Phase 2a Data
2H:2015
More information about clinical trials design can be found at the following links:
(1) ESRD-Pi:
http://clinicaltrials.gov/ct2/show/NCT02081534 (2)
IBS-C: http://clinicaltrials.gov/ct2/show/NCT01923428
(3) CKD: http://clinicaltrials.gov/ct2/show/NCT01847092
|