Clinically and mycologically effective and well-tolerated
oral dose of SCY-078 identified for use in Phase 3 registration
program
Results confirm strong clinical activity of oral SCY-078
and suggest improved sustained benefit relative to the standard of
care, potentially addressing unmet needs in VVC
Initiation of Phase 3 registration program in VVC planned
for the fourth quarter of 2018
Company to host conference call and webcast today at
4:45 PM ET
JERSEY CITY, N.J., July 10, 2018 /PRNewswire/ -- SCYNEXIS, Inc.
(NASDAQ: SCYX), a biotechnology company developing innovative
therapies for difficult-to-treat and often life-threatening
infections, today announced positive results from its Phase
2b, dose-finding study (the DOVE
study) evaluating oral SCY-078 for the treatment of vulvovaginal
candidiasis (VVC). SCY-078, the first representative of a novel
oral and intravenous triterpenoid antifungal family, is in clinical
development for the treatment of multiple serious fungal
infections, including VVC, invasive candidiasis (IC), invasive
aspergillosis (IA) and refractory invasive fungal infections.
The DOVE study evaluated the safety and efficacy of five oral
SCY-078 regimens, with total doses of SCY-078 ranging from 600mg to
1800mg and treatment durations of one or three days, compared to
fluconazole (FLU), the standard of care for VVC. The study enrolled
a total of 186 patients with moderate-to-severe acute VVC
(composite signs and symptoms [S&S] score of seven or higher),
with 153 patients in the culture-confirmed modified Intent-to-Treat
(mITT) population who were assessed at the Day 10 Test-of-Cure
(TOC) visit and at the Day 25 Follow-Up (FU) visit. Key efficacy
parameters included clinical cure rate (primary endpoint) and
mycological eradication; other efficacy evaluations included use of
antifungal rescue therapy and changes of S&S score.
"The DOVE study accomplished its primary goal of identifying a
well-tolerated oral dose regimen of SCY-078 with high clinical cure
and mycological eradication rates," said David Angulo, M.D., Chief Medical Officer of
SCYNEXIS. "The positive effect of oral SCY-078 seen in this study
was achieved at greatly reduced doses and with improved
tolerability compared to our previous VVC Phase 2a study. The
activity of SCY-078 in the DOVE study was consistent with that
observed previously and with the fluconazole reference arm,
providing reassurance of the validity of the findings across
studies and confirming the clinically relevant antifungal
activity of oral SCY-078 in this indication. We are
looking forward to advancing our development program
aiming to provide a much-needed oral treatment alternative for the
growing segment of VVC patients in which current treatment
options are not optimal or not approved, such as those with
complicated cases, infections caused by azole-resistant organisms
and recurrent VVC."
Clinically and Mycologically Effective and Well-Tolerated
Oral Dose Regimen of SCY-078 Identified for Further Development in
VVC Phase 3 Registration Program
- All five doses of oral SCY-078 demonstrated meaningful clinical
and mycological activity, confirming the potent antifungal effect
of SCY-078 observed in our previous VVC Phase 2a study.
- The lowest SCY-078 dose regimen of 600mg exhibited the optimal
combination of overall clinical and mycological activity and
favorable tolerability.
- Pending the End-of-Phase 2 meeting with the U.S. Food and Drug
Administration (FDA), SCYNEXIS believes that the 600mg dose of
SCY-078 (given as two doses of 300mg every 12 hours) is the optimal
dose regimen for use in the VVC Phase 3 registration program.
The SCY-078 Oral Dose Regimen of 600mg Compared Favorably to
the Fluconazole Reference Arm in this Patient Population
- At the Day 10 TOC visit, in the mITT population, clinical cure,
defined as complete resolution of all signs and symptoms, was
observed in 14 of 27 (52%) patients in the SCY-078 600mg dose arm
and 14 of 24 (58%) patients in the FLU arm. At the Day 25 FU visit,
the rate of clinical cure in the SCY-078 600mg dose arm reached 70%
compared to 50% in the FLU arm.
- At the Day 10 TOC visit, in the mITT population, the
mycological eradication rate in the SCY-078 600mg dose arm (63%)
was comparable to the FLU arm (63%). Similar to clinical cure,
mycological eradication at the Day 25 FU visit was numerically
higher in the SCY-078 600mg dose arm (48%) compared to the FLU arm
(38%).
- Additional efficacy observations further confirmed the
sustained clinical benefit of the SCY-078 600mg dose compared to
fluconazole:
-
- Only one of the 27 patients in the SCY-078 600mg dose arm (4%)
required rescue antifungal therapy, compared to seven of the 24
patients in the FLU arm (29%).
- The mean S&S score at the Day 10 TOC visit was 1.0 in the
SCY-078 600mg dose arm vs. 1.8 in the FLU arm. At the Day 25 FU
visit, the mean S&S score was 0.4 in the SCY-078 600mg dose arm
vs. 2.6 in the FLU arm, resulting in a statistically significant
difference (p=0.01) between the two treatments in change from
baseline.
- The oral SCY-078 600mg dose was generally well-tolerated, with
self-limiting (generally one-day duration), mild-to-moderate
gastrointestinal adverse events (AEs) being the most commonly
reported. In the safety population, nausea was reported in three
(10%) subjects in the SCY-078 600mg dose arm compared to two (6%)
in the FLU arm. Diarrhea/loose stool was reported in five (17%)
subjects in the SCY-078 600mg dose arm compared to one (3%) subject
in the FLU arm. Abdominal pain was reported in one (3%) subject in
the SCY-078 600mg dose arm compared to five (16%) subjects in the
FLU arm. No vomiting, severe AEs or discontinuations due to AEs
were reported in the SCY-078 600mg dose arm.
- Results from the efficacy measures of the SCY-078 600mg dose
observed in the DOVE study were in-line with the results observed
from the prior Phase 2a Proof-of-Concept VVC study (reported in
June 2016), which used doses more
than four times higher, further supporting the selection of the
SCY-078 600mg dose for development.
-
- Using the definition of clinical response from the prior Phase
2a VVC study (signs and symptoms composite score of 0 or 1 at Day
25), the clinical response in the SCY-078 600mg dose arm of the
DOVE study was 81% compared to 76% observed for SCY-078 in the
prior Phase 2a VVC study.
Dr. Angulo continued, "The results from the DOVE study come on
the heels of recently shared pre-clinical data suggesting that
SCY-078 has no adverse impact on fertility, embryonic development
or fetal development, a key differentiator versus the current
standard of care for VVC. These results, combined with SCY-078's
fungicidal activity against Candida species, high
penetration into vaginal tissue and enhanced antifungal activity in
the acidic conditions of the vaginal environment, further support
our belief that oral SCY-078 may provide a benefit to many patients
with VVC."
"With limited oral treatment options available for patients with
VVC, and no approved products in recurrent VVC, the results
observed in this Phase 2b study
reinforce SCY-078's potential to address the unmet needs in these
patients," said Marco Taglietti,
M.D., President and Chief Executive Officer of SCYNEXIS. "We look
forward to having our End-of-Phase 2 meeting with the FDA and
starting our Phase 3 registration program for VVC, in which we
anticipate oral SCY-078 will be evaluated for superiority versus
placebo. These results are an important step toward realizing our
goal of maximizing the broad potential of SCY-078 to treat a
multitude of invasive, difficult-to-treat and often
life-threatening fungal infections. I want to take the opportunity
to thank all the patients and investigators who participated in
this Phase 2 trial."
In May 2018, SCYNEXIS announced the receipt of
Qualified Infectious Disease Product (QIDP) and Fast Track
designations from the FDA for the treatment of VVC and prevention
of recurrent VVC. The QIDP designation allows SCYNEXIS to
have priority review and provides an additional five years of
market exclusivity in the U.S. for SCY-078.
The FDA's Fast Track Drug Development Program is a
process designed to facilitate the development and expeditious
review of drugs to treat serious conditions and fill unmet medical
needs.
In June 2018, SCYNEXIS also
announced at the Teratology Society 58th Annual Meeting that
pre-clinical studies provide evidence that SCY-078 does not exhibit
developmental or reproductive toxicity when administered to animals
before and/or during gestation. The absence of teratogenicity is a
critical differentiator for SCY-078, as the majority of currently
available antifungal therapies, including azoles, are associated
with fertility and early embryonic development toxicities.
Conference Call Details
SCYNEXIS will host a
conference call today at 4:45 PM ET
to discuss the results and provide an update on the development
plan of oral SCY-078 for the VVC program. The call can be accessed
by dialing (844) 309-3707 or (661) 378-9467 prior to the start of
the call and referencing conference ID: 8777974. A live webcast of
the conference call will can be accessed on the "Investors" section
of the SCYNEXIS website, www.scynexis.com.
About the DOVE Study
The Phase 2b study was a randomized, multi-center,
double-blind, active-controlled, dose-finding study designed to
evaluate the safety, efficacy, tolerability and pharmacokinetics of
oral SCY-078 compared to oral fluconazole in adult, female patients
with moderate-to-severe acute VVC. A total of 186 patients (ITT)
were randomized to one of five different dosing regimens of oral
SCY-078 or oral fluconazole, the current standard of care treatment
for VVC; a total of 185 patients received at least one dose of
study drug (safety population).
Total Dose
(mg)
|
Regimen
|
ITT /
mITT
|
600mg
SCY-078
|
300mg BID for 1
day
|
30 / 27
|
750mg
SCY-078
|
750mg QD for 1
day
|
32 / 26
|
900mg
SCY-078
|
450mg BID for 1
day
|
28 / 21
|
900mg
SCY-078
|
150mg BID for 3
days
|
32 / 29
|
1800mg
SCY-078
|
300mg BID for 3
days
|
32 / 26
|
150mg
Fluconazole
|
150mg QD for 1
day
|
32 / 24
|
The primary objective of the study was to identify the
recommended dose of oral SCY-078 to advance in the Phase 3 clinical
program. The modified intent to treat (mITT) population was used
for efficacy analysis and included 153 patients with a
culture-confirmed Candida spp. vaginal infection at
baseline. In line with FDA guidance, primary efficacy analysis is
clinical response (i.e., complete resolution of signs and symptoms)
at approximately 10 days after randomization (test-of-cure, TOC)
with other analyses including mycological eradication (i.e.,
negative culture). Patients were assessed also at the Day 25
Follow-Up (FU) visit. Other efficacy evaluations included use of
antifungal rescue therapy and changes of S&S score. The study
was not powered to demonstrate statistically significant
differences for any endpoint and, unless noted otherwise, the
differences reported are not statistically significant. Considering
the limited sample size, statistical significance (i.e., p
value <0.05) reported here is to be interpreted with
caution.
About Vulvovaginal Candidiasis (VVC)
VVC, commonly
known as a "vaginal yeast infection," is the second most common
cause of vaginitis and is usually caused by Candida
albicans. VVC can be associated with substantial morbidity,
including significant genital discomfort, reduced sexual pleasure,
psychological distress and loss of productivity. Typical VVC
symptoms include pruritus, vaginal soreness, irritation and
abnormal vaginal discharge. An estimated 70-75% of women worldwide
will have at least one episode of VVC in their lifetime, and 40-50%
of them will experience two or more episodes. As many as 8% of the
women with VVC suffer from recurrent disease, defined as
experiencing at least three episodes within a 12-month period. VVC
episodes include the following:
- Uncomplicated cases. These are sporadic mild-to-moderate
infections typically caused by C. albicans spp. in a normal
host. They represent the majority of the VVC episodes; and
- Complicated cases. These represent the remaining
episodes and include: severe infections, recurrent cases,
infections caused by non-albicans Candida spp., and/or
observed in an abnormal host.
Current treatments for acute VVC include over-the-counter (OTC)
topical azole antifungals (clotrimazole, miconazole, and others)
and the use of the prescription oral azole antifungal, fluconazole.
Fluconazole is the only orally-administered antifungal currently
approved for acute VVC in the U.S., with a therapeutic cure rate of
55% as reported in its label. Uncomplicated acute VVC cases are
often effectively treated with topical agents and/or with one to
three doses of oral fluconazole. However, management of VVC during
pregnancy, moderate-to-severe VVC, recurrent VVC and VVC caused by
fluconazole-resistant Candida spp. are not fully
addressed by oral fluconazole. In addition, there are no oral
alternatives for VVC patients who do not respond to or tolerate
fluconazole, and there are no FDA-approved products for the
treatment of recurrent VVC.
About SCY-078
SCY-078 is an investigational
antifungal agent that is a semi-synthetic derivative of the natural
product enfumafungin. SCY-078 is the first representative of a
novel class of structurally-distinct glucan synthase inhibitors,
triterpenoids. This agent combines the well-established activity of
glucan synthase inhibitors with the potential flexibility of having
IV and oral formulations. SCY-078 is currently in development for
the treatment of fungal infections caused primarily
by Candida (including C. auris)
and Aspergillus species. It has demonstrated broad
spectrum antifungal activity, in
vitro and in vivo, against multidrug-resistant
pathogens, including azole- and echinocandin-resistant strains.
The FDA has granted QIDP and Fast Track designations for
the formulations of SCY-078 for the indications of IC
(including candidemia), IA, and VVC, and has granted
Orphan Drug Designation for the IC and IA indications.
About SCYNEXIS
SCYNEXIS, Inc. (NASDAQ: SCYX) is a
biotechnology company committed to positively impacting the lives
of patients suffering from difficult-to-treat and often
life-threatening infections by developing innovative therapies.
The SCYNEXIS team has extensive experience in the
life sciences industry, discovering and developing more than 30
innovative medicines over a broad range of therapeutic areas. The
Company's lead product candidate, SCY-078, is a novel IV/oral
antifungal agent in Phase 2 clinical development for the treatment
of multiple serious and life-threatening invasive fungal infections
caused
by Candida and Aspergillus species.
For more information, visit www.scynexis.com.
Forward Looking Statement
Statements contained in this
press release regarding expected future events or results,
including but not limited to the Company's plans regarding clinical
developments and possible initiation of a Phase 3 registration
program in VVC, are "forward-looking statements" within the meaning
of the Private Securities Litigation Reform Act of 1995. Because
such statements are subject to risks and uncertainties, actual
results may differ materially from those expressed or implied by
such forward-looking statements. These risks and uncertainties
include, but are not limited, to: risks inherent
in SCYNEXIS's ability to successfully develop and
obtain FDA approval for SCY-078; the expected costs of
studies and when they might begin or be concluded;
and SCYNEXIS's reliance on third parties to
conduct SCYNEXIS's clinical studies. These and other
risks are described more fully in SCYNEXIS's filings with
the Securities and Exchange Commission, including without
limitation, its most recent Annual Report on Form 10-K under the
caption "Risk Factors" and 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. SCYNEXIS undertakes no obligation to update such
statements to reflect events that occur or circumstances that exist
after the date on which they were made.
CONTACT:
Investor Relations
Natalie
Wildenradt
Argot Partners
Tel: 212-600-1902
natalie@argotpartners.com
Media Relations
George E.
MacDougall
MacDougall Biomedical Communications
Tel: 781-235-3093
george@macbiocom.com
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