Sienna Biopharmaceuticals Announces Its Topical, Non-Steroid TrkA Inhibitor SNA-120 (0.05%) Demonstrated Significant Impact on Psoriasis in Phase 2b Study and Plans to Initiate Phase 3 Psoriasis Trials

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.