-- 27% of subjects achieved 75% reduction in PASI
score (PASI 75) vs 13% with vehicle; 29% of subjects achieved
two-grade improvement on IGA and ‘clear’ or ‘almost clear’ skin vs
13% with vehicle (statistically significant)
Sienna Biopharmaceuticals, Inc. (NASDAQ:SNNA), a clinical-stage
medical dermatology and aesthetics company, today announced
top-line results from a Phase 2b study of SNA-120 (pegcantratinib),
the Company’s lead drug candidate developed using its proprietary
Topical by Design™ platform. This Phase 2b study, in
mild-to-moderate psoriasis patients with at least moderate pruritus
(itch), was designed to assess the efficacy and safety of SNA-120
on itch (primary endpoint), as well as the underlying psoriasis
(secondary endpoints). In this study, subjects treated with
SNA-120 (0.05%) achieved statistical significance, compared to
vehicle, on important pre-specified regulatory endpoints of
psoriasis disease severity. Subjects treated with SNA-120
also experienced a meaningful reduction in itch, although the
result did not reach statistical significance against vehicle.
SNA-120 is a topical tropomyosin receptor kinase
A (TrkA) inhibitor that blocks nerve growth factor (NGF) signaling,
which plays an important role in the pathogenesis of psoriasis and
itch. SNA-120 was developed using Sienna’s Topical by Design™
platform, which yields new chemical entities (NCEs) designed to
deliver high local drug concentration in the target tissue with
minimal to no systemic exposure for patients.
Sienna’s multicenter, randomized, double-blind,
vehicle-controlled Phase 2b study evaluated the safety and efficacy
of two doses (0.05% and 0.5%) of SNA-120 ointment in 208 male and
female patients over the age of 18 with mild-to-moderate psoriasis
and with at least moderate itch. Subjects were randomized
into three groups and administered a high dose (0.5%) of SNA-120, a
low dose (0.05%) of SNA-120 or vehicle twice daily for 12
weeks.
The primary endpoint of the study was mean
change from baseline to week eight on the Itch Numeric Rating Scale
(I-NRS). The I-NRS is an 11-point scale ranging from ‘no
itch’ (0) to the ‘worst imaginable itch’ (10) that study
participants used daily to report the intensity of their worst itch
in the previous 24 hours. Patients treated with SNA-120
(0.05%) experienced a mean 4.3 point (58%) reduction from baseline
on the I-NRS, compared to a mean 4.0 point (55%) reduction with
vehicle (not statistically significant, p=0.244). SNA-120
(0.5%) showed similar results.
On pre-specified, key secondary endpoints
related to the clearance of psoriatic plaques, SNA-120 (0.05%)
demonstrated statistically significant and clinically meaningful
improvements. Specifically, 27% of subjects experienced a 75%
reduction in their Psoriasis Area and Severity Index (PASI 75)
score from baseline, compared to 13% of subjects treated with
vehicle (p=0.045). The study also included an Investigator
Global Assessment (IGA), in which 29% of patients achieved a
two-grade improvement and ‘clear’ or ‘almost clear’ skin, compared
to 13% of subjects treated with vehicle (p=0.036). Both
the PASI 75 and IGA results remained statistically
significant at 14 weeks, two weeks after discontinuation of
treatment. The high dose (0.5%) of SNA-120 did not show
statistical significance on these study endpoints.
SNA-120 was well-tolerated with no serious
treatment-related adverse events. Treatment-related adverse
events were observed in two patients and included dermatitis (0.5%
group) and pain and pruritus (vehicle group). SNA-120 has now
been tested in more than 500 patients and has been consistently
well tolerated with a safety profile that further validates
Sienna’s Topical by Design™ platform.
“These results, although not entirely as we
expected, are very exciting. While we did not meet our
primary endpoint on pruritus, SNA-120 demonstrated statistically
significant and clinically meaningful effects on key secondary
psoriasis endpoints that were greater than anticipated,” said
Frederick C. Beddingfield III, MD, PhD, President and Chief
Executive Officer of Sienna Biopharmaceuticals. “In addition
to its significant effect on psoriatic plaques, SNA-120 reduced
itch by 58%, although it did not separate from vehicle. This
may be partially due to the beneficial emollient effect of the
vehicle and the inherent variability in patient-reported
assessments. Taken together, these results demonstrate the
potential of SNA-120 as a novel topical, non-steroidal treatment
for psoriasis. Moving ahead, we plan to pursue a psoriasis
indication for SNA-120 with pruritus measured as a secondary
endpoint. We expect to start our Phase 3 studies for
psoriasis in the second half of 2019.”
Local peripheral nerves in the
skin play an important role in the pathogenesis of
psoriasis, as the absence of neural input has been shown to
lead to plaque clearance. Plaques in psoriasis patients with
associated itch have elevated levels of NGF-immunoreactive
keratinocytes and TrkA expression in innervating nerve
fibers. The NGF/TrkA signaling pathway is important in
neurogenic inflammation and keratinocyte hyperproliferation which
contribute to psoriatic plaques, as well as itch.
“SNA-120 selectively targets the NGF-TrkA
signaling pathway,” said Paul F. Lizzul, MD, PhD, Chief Medical
Officer of Sienna Biopharmaceuticals. “In our second Phase 2b
study, we enrolled psoriasis patients with at least moderate
itch, which may be a proxy for elevated NGF/TrkA activation.
We believe, based on our evolving understanding of the
importance of neurogenic inflammation in
psoriasis, that enriching the patient population in this
study and specifically targeting the NGF-TrkA signaling
pathway within the plaque contributed to the observed effects of
SNA-120, on both PASI 75 and composite IGA.”
“These are promising results for an innovative,
non-steroidal, topical treatment for the large majority of
psoriasis patients who have mild-to-moderate disease but are not
candidates for systemic therapies,” said Alan Menter, Chair of
dermatology at Baylor Scott & White, Dallas, Principle Faculty
at Texas A&M University Health Science Center, and a clinical
professor of dermatology at the University of Texas Southwestern
Medical School. “Given the safety profile observed in this
Phase 2 study, SNA-120 could also potentially address the unmet
need for treating sensitive areas such as the face and skin
folds. If these results are replicated in Phase 3 studies,
this type of innovation could be of significant interest to
physicians and patients with mild-to-moderate psoriasis.”
SNA-125 Phase 1/2 Study in Atopic
Dermatitis
Sienna also announced results from an exploratory Phase 1/2
study of its investigational new chemical entity SNA-125, a
JAK3/TrkA inhibitor being evaluated as a first-in-class topically
administered medication to treat atopic dermatitis. JAK3
inhibition blocks the signaling of key cytokines, resulting in
reduced severity of certain autoimmune and inflammatory
diseases.
This early-stage randomized, double-blind, vehicle-controlled,
intra-individual study, using a target lesion model, was designed
to evaluate the safety and efficacy of SNA-125 gel in 30 patients
with atopic dermatitis. The study compared a high dose (2%) and a
low dose (0.2%) of SNA-125 with a vehicle and an active control.
Subjects were treated in the clinic once daily for 14 days, with
each treatment topically applied to a small and distinct
area.
In this study, SNA-125 was well tolerated and showed no safety
signals in both healthy subjects and patients with atopic
dermatitis, with no serious adverse events reported. The most
common treatment-related adverse events were pain and
pruritus. Similar small reductions in clinical scores of
target lesions were observed for both SNA-125 and vehicle; however,
certain histological and biomarker changes indicated a modest drug
effect with SNA-125. The Company plans to initiate a Phase 2
study with SNA-125 in atopic dermatitis in the second half of
2019.
Conference Call and Webcast
Sienna will host a conference call today,
December 3, at 8:15 a.m. Eastern Time to discuss the SNA-120 Phase
2b trial results. Callers should dial in approximately 10 minutes
prior to the start of the call. No reservation is necessary
to participate on the call. The phone number to join the
conference call is +1 (877) 376-9929 (toll-free in the United
States and Canada) or +1 (629) 228-0733 (international). The
conference identification number for the live call is 6081337.
The call will be webcast live and can be
accessed through the Investor Relations section of the Company’s
website at Investors.SiennaBio.com. An archived version of the
webcast will be available approximately two hours following the
live call for 90 days.
About Sienna’s Topical by Design™ Platform
Topical by Design™ is an innovative
platform, designed to enable the topical application of potent
active pharmaceuticals against known biologic targets while
minimizing exposure to the systemic circulation, thereby addressing
the tolerability trade-offs that often make therapies unsuitable
for use in larger segments of the population with less severe
disease. Topical by Design™ applies a scientific design
process to transform molecules into NCEs by stabily linking a short
polyethylene glycol (PEG) polymer to a pharmacologically active
molecule. Applying this technology, we have created a
pipeline of drug candidates with unique pharmacological
profiles to manage a variety of chronic inflammatory and
immunologic conditions. Applications for the Topical by
Design™ platform are currently being explored with SNA-120 for use
in psoriasis, and SNA-125 for use in atopic dermatitis, psoriasis
and pruritus.
About Sienna Biopharmaceuticals
Sienna Biopharmaceuticals, Inc. is a
clinical-stage biopharmaceutical company focused on bringing
innovations in biotechnology to the discovery, development and
commercialization of first-in-class, targeted, topical products in
medical dermatology and aesthetics. The Company’s objective is to
develop a unique, diversified, multi-asset pipeline of topical
therapies that enhance the health, appearance and quality of life
of dermatology and aesthetics patients. Sienna is led by a
management team with extensive experience in product development
and commercialization at several leading dermatology, aesthetics
and biotechnology companies.
For more information, visit the Company’s
website at www.SiennaBio.com.
Forward-Looking Statements
This press release contains forward-looking
statements, including but not limited to statements by Sienna’s
Executive Officers and Alan Mentor, M.D. regarding Sienna’s
expectations for SNA-120, including the potential for SNA-120 to be
an effective treatment for psoriasis and the initiation of Phase 3
clinical trials, as well as Sienna’s expectations for additional
data readouts for its clinical trials. Such forward-looking
statements involve substantial risks and uncertainties that could
cause Sienna’s clinical development programs, future results,
performance, or achievements to differ significantly from those
expressed or implied by the forward-looking statements. Such risks
and uncertainties include, among others, the uncertainties inherent
in the pharmaceutical drug and medical device development
processes, including the clinical development process, regulatory
approval processes, the timing of regulatory filings, the
challenges associated with manufacturing pharmaceutical drug and
medical device products, Sienna’s ability to successfully protect
and defend its intellectual property, and other matters that could
affect the sufficiency of existing cash to fund operations and the
availability or commercial potential of Sienna’s drug candidates.
Sienna undertakes no obligation to update or revise any
forward-looking statements. For a further description of the risks
and uncertainties that could cause actual results to differ from
those expressed in these forward-looking statements, as well as
risks relating to the business of the Company in general, see
Sienna’s most recent Annual Report on Form 10-K and any subsequent
current and periodic reports filed with the Securities and Exchange
Commission.
Contact:
MediaCaroline Van
Hovecvanhove@siennabio.com818-575-6250
Crystal Muilenburgcmuilenburg@siennabio.com818-584-1035
InvestorsSean
Andrewssandrews@siennabio.com818-629-2244
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