Cara Therapeutics Announces Dosing of Patients in Phase 2 Trial of Oral KORSUVA™ (CR845/difelikefalin) for Pruritus in Stag...
July 11 2018 - 7:00AM
Cara Therapeutics, Inc. (Nasdaq:CARA), a biopharmaceutical company
focused on developing and commercializing new chemical entities
designed to alleviate pruritus and pain by selectively targeting
peripheral kappa opioid receptors, today announced that the first
patients have been dosed in a Phase 2 trial of Oral KORSUVA
(CR845/difelikefalin) for the treatment of pruritus in stage III-V
(moderate-to-severe) CKD patients. CKD-associated pruritus (CKD-aP)
is a condition that affects approximately 25% of pre-dialysis CKD
patients, for which there are currently no approved therapies in
the U.S.
“The initiation of this Phase 2 trial in
pre-dialysis CKD patients is an important milestone in the
development of Oral KORSUVA as a potential novel treatment option
for moderate-to-severe pruritus in this patient population,” said
Derek Chalmers, Ph.D., D.Sc., President and Chief Executive Officer
of Cara Therapeutics. “Throughout the remainder of this year, we
plan to expand our clinical activities with Oral KORSUVA beyond CKD
into additional patient populations, such as those with chronic
hepatic and dermatologic conditions, in which treatment-resistant
pruritus also remains a significant unmet medical need.”
Phase 2 Trial Design
The Phase 2, multicenter, randomized,
double-blind, placebo-controlled 12-week trial is designed to
evaluate the safety and efficacy of three dose levels (0.25 mg, 0.5
mg and 1 mg, once daily) of Oral KORSUVA versus placebo in
approximately 240 stage III-V CKD patients with moderate-to-severe
pruritus. The sample size may be increased up to 480 patients (120
per treatment group) based on the results of an interim analysis
that will be conducted when approximately 50% of the planned 240
patients have completed the 12-week treatment period.
The primary efficacy endpoint is the change from
baseline in the weekly mean of the daily 24-hour Worst Itch
Numeric Rating Scale (NRS) score at Week 12 of the treatment
period. Secondary endpoints include change from baseline in
itch-related quality of life scores at the end of Week 12, as
assessed by the total Skindex-10 and 5-D itch scales, as well as
the proportion of patients achieving an improvement from baseline
≥3 points with respect to the weekly mean of the daily 24-hour
Worst Itch NRS score at week 12.
Top-Line Results from
Phase 1 Pharmacokinetic Trial of Oral KORSUVA in
Moderate-to-Severe CKD Patients
The Phase 1, open-label trial was designed to
evaluate the safety and pharmacokinetic (PK) profile of once-daily
doses of Oral KORSUVA administered over a period of one week to CKD
patients with moderate or severe renal impairment. Once-daily
dosing with Oral KORSUVA tablets of 0.25 mg, 0.5 mg or 1.0 mg was
evaluated sequentially in three groups of patients with moderate
renal impairment and three groups of patients with severe renal
impairment (six groups total). PK blood samples were collected at
prespecified time points during the treatment period after the
study drug was administered. The graph below is representative of
Day 1 exposure of Oral KORSUVA as represented by area under the
curve (AUC).
The exposure levels demonstrated with Oral
KORSUVA tablets were approximately equivalent to the exposure level
achieved with 0.5 mcg/kg dose of I.V. KORSUVA that exhibited
statistically significant and clinically meaningful reduction in
itch intensity in hemodialysis patients with moderate to severe
CKD-aP. The efficacy and safety data from the previous Phase 2
trial of I.V. KORSUVA in dialysis patients with CKD-aP were
presented at the 2017 American Society of Nephrology’s Annual
Meeting.
A photo accompanying this announcement is available at
http://www.globenewswire.com/NewsRoom/AttachmentNg/d02918dc-ebcf-4856-9197-5e53bf036a5f
About KORSUVA for the Treatment of
CKD-Associated Pruritus (CKD-aP)
The U.S. Food and Drug Administration (FDA) has
granted Breakthrough Therapy designation to I.V. CR845 for the
treatment of moderate-to-severe pruritus in CKD patients undergoing
hemodialysis. Breakthrough Therapy designation is granted to
expedite the development and review process for new therapies
addressing serious or life-threatening conditions where preliminary
clinical evidence indicates that the drug candidate may demonstrate
substantial improvement over existing therapies on one or more
clinically significant endpoints. There are currently no
FDA-approved drugs for the treatment of CKD-aP.
The FDA has conditionally accepted KORSUVA™ as
the trade name for difelikefalin injection. CR845/difelikefalin is
an investigational drug product and its safety and efficacy have
not been fully evaluated by any regulatory authority.
About CKD-Associated
Pruritus (CKD-aP)
CKD-aP is an intractable systemic itch condition
that occurs with high frequency and intensity in patients with CKD
undergoing hemodialysis and peritoneal dialysis. Pruritus has also
been reported in patients with stage III-V CKD who are not on
dialysis. According to estimates from the Centers for Disease
Control and Prevention, approximately 15% of the adult population
in the United States, or 30 million people, suffer from CKD, with
an estimated 50% in stages III-V. Of the patients diagnosed with
stage III-V CKD, approximately 25% suffer from moderate-to-severe
pruritus. Recent data from the ITCH National Registry Study showed
that among those with pruritus, approximately 59% experienced
symptoms daily or nearly daily for more than a year. Given its
association with CKD/end-stage renal disease, most afflicted
patients will continue to have symptoms for months or years with
currently employed antipruritic treatments, such as antihistamines
and corticosteroids, which are unable to provide consistent,
adequate relief. Moderate-to-severe chronic pruritus has repeatedly
been shown to directly decrease quality of life, contribute to
symptoms that impair quality of life (such as poor sleep quality),
and is associated with depression.
References:
- Centers for Disease Control and Prevention: Chronic Kidney
Disease (CKD) Surveillance Project. National Health and Nutrition
Examination Survey. 2014.
- Sukul N, et al. Pruritus in Chronic Kidney Disease Patients:
Early Results from CKDopps. ERA-EDTA Abstract. December 2016.
- IMS Pruritus Market Landscape Analysis. September
2014.
- Pisoni RL, et al. Pruritus in haemodialysis patients:
international results from the Dialysis Outcomes and Practice
Patterns Study (DOPPS). Nephrol Dial Transplant. 2006;
21:3495-3505.
- Ramakrishnan, et al. Clinical characteristics and outcomes of
end-stage renal disease patients with self-reported pruritus
symptoms. International Journal of Nephrology and Renovascular
Disease. 2014; 7: 1-12.
- Mathur VS, et al. A longitudinal study of uremic pruritus in
hemodialysis patients. Clin J Am Soc Nephrol. 2010;
5(8):1410-1419.
About Cara Therapeutics
Cara Therapeutics is a clinical-stage
biopharmaceutical company focused on developing and commercializing
new chemical entities designed to alleviate pruritus and pain by
selectively targeting peripheral kappa opioid receptors (KORs).
Cara is developing a novel and proprietary class of product
candidates, led by KORSUVA™ (CR845/difelikefalin), a first-in-class
KOR agonist that targets the body's peripheral nervous system, as
well as certain immune cells. In Phase 2 trials, KORSUVA injection
has demonstrated statistically significant reductions in itch
intensity and concomitant improvement in quality of life measures
in hemodialysis patients with moderate-to-severe chronic kidney
disease-associated pruritus (CKD-aP), and is currently being
investigated in Phase 3 trials in hemodialysis patients with
CKD-aP. Additionally, in a recently completed Phase 2/3 trial in
post-operative patients, I.V. CR845/difelikefalin has demonstrated
reduction in moderate-to-severe pain, while also reducing the
incidence and intensity of nausea and vomiting throughout the
post-operative period.
Forward-looking Statements
Statements contained in this press release
regarding matters that are not historical facts are
"forward-looking statements" within the meaning of the Private
Securities Litigation Reform Act of 1995. Examples of these
forward-looking statements include statements concerning the
potential of Oral KORSUVA (CR845/difelikefalin) as a treatment for
moderate-to-severe pruritus in stage III-V CKD patients, the
planned expansion of clinical activities with Oral KORSUVA
(CR845/difelikefalin) beyond CKD patients into additional
populations, or the potential of Oral KORSUVA (CR845/difelikefalin)
to be a treatment option for such patients. Because such statements
are subject to risks and uncertainties, actual results may differ
materially from those expressed or implied by such forward-looking
statements. Risks are described more fully in Cara Therapeutics'
filings with the Securities and Exchange Commission, including the
"Risk Factors" section of the Company's Annual Report on Form 10-K
for the year ended December 31, 2017, and its other documents
subsequently filed with or furnished to the Securities and Exchange
Commission. All forward-looking statements contained in this press
release speak only as of the date on which they were made. Cara
Therapeutics undertakes no obligation to update such statements to
reflect events that occur or circumstances that exist after the
date on which they were made.
MEDIA CONTACT: Annie Starr 6 Degrees
973-415-8838 astarr@6degreespr.com
INVESTOR CONTACT: Michael Schaffzin Stern
Investor Relations, Inc. 212-362-1200 michael@sternir.com
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