Efficacy and safety of apremilast in systemic- and biologic-naive patients with moderate plaque psoriasis (52-week results of the UNVEIL study)

Efficacy and safety of apremilast in systemic- and biologic-naive patients with moderate plaque psoriasis (52-week results of the UNVEIL study)

Presenters: Strober B1, Forman S2, Bagel J3, Lebwohl M4, Stein Gold L5, Jackson JM6, Goncalves J7, Levi E7, Callis Duffin K8

Affiliations: 1University of Connecticut, Farmington, CT, and Probity Medical Research, Waterloo, ON, Canada; 2Forward Clinical Trials, Tampa, FL; 3Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ; 4Icahn School of Medicine at Mount Sinai, New York, NY; 5Henry Ford Health System, West Bloomfield, MI; 6University of Louisville, Forefront Dermatology, Louisville, KY; 7Celgene Corporation, Summit, NJ; 8University of Utah, Salt Lake City, UT

Background/Objective: Patients with moderate plaque psoriasis (i.e., 5–10% psoriasis-involved Body Surface Area [BSA]) often receive no treatment or are undertreated with topical monotherapy. Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has been shown to be effective and has demonstrated acceptable tolerability in patients with moderate-to-severe psoriasis (BSA 10%) in the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) Phase III clinical trial program. Evaluating Apremilast in a Phase IV Trial of Efficacy and Safety in Patients With Moderate Plaque Psoriasis (UNVEIL) (ClinicalTrials.gov: NCT02425826) is the first prospective randomized, placebo (PBO)-controlled trial to demonstrate the clinical efficacy and safety of an oral systemic treatment (apremilast) in systemic- and biologic-naive patients with moderate plaque psoriasis. Apremilast 30mg twice-daily (APR) was clinically effective and well tolerated during the 16-week, double-blind, PBO-controlled phase. The efficacy and safety results of the open-label APR treatment phase up to Week 52 are presented.

Methods: UNVEIL is a Phase IV, multicenter, randomized, PBO-controlled, double-blind study. Men and women at least 18 years of age with chronic plaque psoriasis for six months before screening were included in the study. Subjects had moderate plaque psoriasis at screening and baseline as defined by BSA of 5 to 10 percent and static Physician’s Global Assessment (sPGA) of 3 (moderate) based on a scale ranging from 0 (clear) to 5 (very severe). Included subjects had no prior exposure to systemic or biologic treatments for psoriasis, psoriatic arthritis, or any other condition that could affect the assessment of psoriasis. Potential subjects with an inflammatory or dermatologic condition, including forms of psoriasis other than plaque psoriasis, were excluded. Persons using topical therapy within two weeks or phototherapy within four weeks of randomization were also excluded. Patients were randomized (2:1) to receive APR or PBO during Weeks 0 to 16; patients in the PBO group were switched to APR at Week 16. All patients continued taking APR through Week 52.

The primary efficacy endpoint was the mean percentage change from baseline at Week 16 in PGAxBSA, which represents the product of sPGA and BSA scores. Overall BSA affected by psoriasis is estimated based on the patient’s palm area, which equates to approximately one percent of total BSA. For the 6-point sPGA for plaques in all involved areas, the severity of erythema, scaling, and plaque elevation were each scored; scores were averaged and rounded to the nearest whole number. The secondary efficacy endpoint was the proportions of patients achieving a 75-percent reduction from baseline in PGAxBSA score (PGAxBSA-75) and the sPGA response, defined as a score of 0 (clear) or 1 (almost clear). Quality of life (QOL) was assessed with the Dermatology Life Quality Index (DLQI). Safety was evaluated based on adverse events (AEs), vital signs, clinical laboratory testing, and complete physical examinations. Efficacy and QOL assessments were conducted for the intent-to-treat (ITT) population, which included all randomized patients; safety assessments were conducted in all randomized patients who received one dose of study medication. Mean percentage change from baseline in PGAxBSA and change from baseline in DLQI total score at Week 16 were compared between APR and PBO using a two-sided analysis of covariance model (ANOVA) with treatment and site as factors and baseline value as covariate. PGAxBSA-75 and sPGA responses at Week 16 were evaluated with two-sided Cochran-Mantel-Haenszel tests stratified by site. Efficacy and QOL parameters at Week 52 were evaluated descriptively. Week 16 and Week 52 APR/APR analyses were performed with the ITT population. Week 52 PBO/APR analyses were performed with the modified ITT population (all patients who entered the APR extension phase). The last-observation-carried-forward methodology was used to impute missing values. Safety assessments were summarized using frequencies and percentages.

Results: A total of 221 patients were randomized to study treatment and constitute the ITT population; 185 patients (84%) completed the PBO-controlled phase (Weeks 0–16) and 136/185 patients (74%) completed the APR treatment phase (Weeks 16–52). Demographics and baseline disease characteristics were generally similar between treatment groups. At baseline, mean DLQI total score was comparable between treatment groups, and the mean pruritus Visual Analog Scale (VAS) score was slightly higher in the PBO group. At Week 16, significantly greater improvement in PGAxBSA occurred in patients receiving APR (-48.1%) versus PBO (-10.2%). At Week 52, improvement was maintained in the APR/APR group and emerged in the PBO/APR group after switching to APR. Significantly more patients treated with APR achieved PGAxBSA-75 response at Week 16 (35.4%) versus PBO (12.3%). PGAxBSA-75 response was maintained in the open-label APR treatment phase. Significantly more patients treated with APR achieved an sPGA score of 0 or 1 at Week 16 (30.4%) versus PBO (9.6%). Long-term sPGA response was maintained with APR treatment in the open-label treatment phase. Improvement in DLQI was significantly greater with APR (-4.8) than PBO (-2.4) at Week 16. DLQI improvement was maintained in patients continuing on APR for up to 52 weeks and developed after patients were switched from PBO to APR. Most AEs were mild or moderate. The most common AEs (reported in 5% of patients in either treatment group during the PBO-controlled period) included diarrhea, headache, nausea, upper respiratory tract infection, decreased appetite, and vomiting.

Conclusion: APR was clinically effective in systemic- and biologic-naive patients with moderate plaque psoriasis (BSA of 5–10%). APR significantly improved PGAxBSA score, PGAxBSA-75 response rate, sPGA 0 or 1 response rate, and DLQI total score at Week 16 compared with PBO. Clinical responses were maintained with continued APR treatment through Week 52 and emerged in patients who switched from PBO to APR at Week 16. The incidence of AEs, based on EAIR per 100 patient-years, did not increase with longer exposure to APR. Safety and tolerability were consistent with previous studies; no new safety or tolerability issues were observed up to 52 weeks.

Funding/Disclosures: The authors acknowledge financial support for this study from Celgene Corporation. Bruce Strober receives honoraria as a consultant, payments (to the University of Connecticut) as an investigator, and is an advisory board member of Celgene Corporation. Seth Forman receives research support from the Celgene Corporation. Jerry Bagel is an advisory board member, speaker, consultant, and/or receives research support from the Celgene Corporation. Mark Lebwohl is an investigator and/or consultant for the Celgene Corporation. J. Mark Jackson receives research, honoraria, consulting, and/or other support from Celgene Corporation. Joana Goncalves and Eugenia Levi are employees of the Celgene Corporation. Kristina Callis Duffin is a consultant, steering committee member, advisory board member, has received grants, and/or has received honoraria from the Celgene Corporation.

Improvement in scalp and nails with apremilast in patients with moderate plaque psoriasis naive to systemic and biologic therapy: 52-week results of the UNVEIL study.

Improvement in scalp and nails with apremilast in patients with moderate plaque psoriasis naive to systemic and biologic therapy: 52-week results of the UNVEIL study.

Presenters: Jackson JM1, Alikhan A2, Lebwohl M3, Stein Gold L4, Levi E5, Bagel J6,

Affiliations: 1University of Louisville, Forefront Dermatology, Louisville, KY; 2University of Cincinnati, Department of Dermatology, Cincinnati, OH; 3Icahn School of Medicine at Mount Sinai, New York, NY; 4Henry Ford Health System, West Bloomfield, MI; 5Celgene Corporation, Summit, NJ; 6Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ

Background/Objective: Patients with moderate plaque psoriasis (i.e., 5–10% psoriasis-involved Body Surface Area [BSA]) often receive no treatment or are undertreated with topical monotherapy. Plaque psoriasis that occurs in difficult-to-treat areas such as the scalp and nails might be disproportionately more distressing to patients because it is highly visible and can severely impact daily functioning. Apremilast is an oral, small-molecule phosphodiesterase 4 inhibitor that works intracellularly to regulate inflammatory pathways relevant to the pathogenesis of psoriasis. Apremilast has been shown to be effective and has demonstrated acceptable tolerability in Phase IV clinical studies in patients with moderate-to-severe psoriasis. Evaluating Apremilast in a Phase IV Trial of Efficacy and Safety in Patients With Moderate Plaque Psoriasis (UNVEIL; ClinicalTrials.gov: NCT02425826) is the first prospective, randomized, placebo (PBO)-controlled trial to demonstrate the clinical efficacy and safety of a systemic treatment (apremilast) in systemic- and biologic-naive patients with moderate plaque psoriasis. To further understand the efficacy of apremilast in patients with moderate plaque psoriasis, analyses were performed in the subset of patients with baseline scalp and/or nail involvement.

Methods: UNVEIL is a Phase IV, multicenter, randomized, PBO-controlled, double-blind study. Men and women at least 18 years of age with chronic plaque psoriasis for six months before screening were included in the study. Subjects had moderate plaque psoriasis at screening and baseline as defined by BSA of 5 to 10 percent and static Physician’s Global Assessment (sPGA) of 3 (moderate) based on a scale ranging from 0 (clear) to 5 (very severe). Included subjects had no prior exposure to systemic or biologic treatments for psoriasis, psoriatic arthritis, or any other condition that could affect the assessment of psoriasis. Potential subjects with an inflammatory or dermatologic condition, including forms of psoriasis other than plaque psoriasis, were excluded. Persons using topical therapy within two weeks or phototherapy within four weeks of randomization were also excluded. Patients were randomized (2:1) to receive apremilast 30mg twice daily (APR) or PBO during Weeks 0 to 16; patients in the PBO group were switched to APR at Week 16. All patients continued taking APR through Week 52. A nonmedicated moisturizer was the only topical therapy permitted during the study.

Patients with a baseline Scalp Physician Global Assessment (ScPGA) score of 1 or a Nail Psoriasis Severity Index (NAPSI) score of 1 in the target nail were included in subanalyses of scalp and nail involvement. ScPGA was assessed on a 6-point scale ranging from 0 (clear) to 5 (very severe). One thumbnail or fingernail with the worst nail psoriasis involvement at baseline was designated as the target nail. NAPSI score was calculated in the target nail as the sum of scores for the nail matrix and nail bed, with each score based on the number of quadrants with psoriasis features. Efficacy assessments in patients with scalp psoriasis at baseline included proportion of patients achieving ScPGA score of 0 (clear) or 1 (minimal), with a 2-point reduction from baseline score, at Week 16 and Week 52. Efficacy assessments in patients with nail psoriasis at baseline included change from baseline in NAPSI score at Week 16 and Week 52, proportion of patients achieving a 50-percent reduction from baseline in NAPSI score (NAPSI-50) at Week 16 and Week 52. Safety was evaluated based on adverse events (AEs), vital signs, clinical laboratory testing, and complete physical examinations. Efficacy and safety assessments were conducted for the intent-to-treat (ITT) population, which included all randomized patients; safety assessments included all patients who received one dose of study medication. The proportions of patients achieving ScPGA and NAPSI-50 responses were compared between the PBO and APR groups at Week 16 using a two-sided Cochran-Mantel-Haenszel test stratified by site. Changes from baseline in NAPSI score at Week 16 were compared between treatment groups using a two-way analysis of covariance (ANCOVA) model with treatment and site as factors and baseline value as a covariate. Efficacy parameters at Week 52 were evaluated descriptively. The last-observation-carried-forward (LOCF) methodology was used to impute missing values. Safety assessments were summarized using frequencies and percentages.

Results: A total of 221 patients were randomized to study treatment. Of these, 167 patients (75.6%) had scalp psoriasis and 83 patients (37.6%) had nail psoriasis at baseline. Demographic and baseline disease characteristics of the cohorts with scalp psoriasis or nail psoriasis were generally comparable between treatment groups. Mean baseline NAPSI scores were comparable between treatment groups. Across treatment groups, most patients had mild or moderate scalp involvement (i.e., ScPGA score of 2 or 3). Regarding efficacy of APR in scalp psoriasis, at Week 16, more patients treated with APR than with PBO achieved an ScPGA score of 0 or 1 with a 2-point reduction from baseline (38.4% vs. 20.0%, P=0.0178). At Week 52, patients remaining on APR maintained ScPGA response, and those who switched to APR from PBO at Week 16 (PBO/APR) demonstrated an improvement in ScPGA response comparable to those who continued APR treatment (APR/APR). An ScPGA score of 0 or 1 with a 2-point reduction from baseline was achieved by 47.7 percent of patients randomized to APR who continued on APR (APR/APR), and 46.9 percent of patients randomized to PBO who switched to APR (PBO/APR). Regarding the efficacy of APR in nail psoriasis, at Week 16, the mean percentage change from baseline in NAPSI score was -10.5 percent in the PBO group and -28.9 percent in the APR group (P=0.12). At Week 52, continued improvement in NAPSI score was seen in patients who remained on APR treatment (mean percentage change from baseline, -51.9%). Patients who switched from PBO to APR at Week 16 demonstrated an improvement in NAPSI score (mean percentage change from baseline, -52.7%). At Week 16, NAPSI-50 response was achieved by 18.5 percent of patients in the PBO group and 26.8 percent of patients in the APR group (P=0.50). Although differences in NAPSI-50 response with APR compared with PBO are numerically greater, the number of patients with nail psoriasis at baseline was low and thus statistical significance was not demonstrated. At Week 52, the proportion of patients who achieved NAPSI-50 response increased in patients who remained on APR treatment and in patients who switched to APR from PBO at Week 16.

The most common AEs reported with APR treatment from 0 to 52 weeks were diarrhea, nausea, headache, and nasopharyngitis. Most AEs were mild or moderate; discontinuations due to AEs occurred in 6.6 percent of patients over the 52-week study. The incidence of AEs, based on exposure-adjusted incidence rate (EAIR) per 100 patient-years, did not increase with longer exposure up to 52 weeks when compared with Weeks 0 to 16. No new safety or tolerability issues were observed up to 52 weeks.

Conclusion: APR treatment improved scalp and nail psoriasis at Week 16 in systemic- and biologic-naive patients with moderate plaque psoriasis (BSA 5–10%); continued improvement was seen with APR treatment up to 52 weeks. The efficacy of APR on scalp and nail psoriasis was consistent with that previously reported in patients with moderate-to-severe plaque psoriasis in randomized Phase III trials. The safety and tolerability profile of APR was also consistent with previous studies.

Funding/Disclosures: The authors acknowledge financial support for this study from Celgene Corporation. J. Mark Jackson provides research, honoraria, consulting, and/or other support to the Celgene Corporation. Ali Alikhan is a former speaker for Celgene Corporation. Mark Lebwohl is an investigator and/or consultant for the Celgene Corporation. Linda Stein Gold is an investigator and/or consultant for the Celgene Corporation. Joana Goncalves and Eugenia Levi are employees of the Celgene Corporation. Jerry Bagel is an advisory board member, speaker, consultant, and/or provides research support to the Celgene Corporation.

Sustained improvement in patient-reported outcomes with continued apremilast treatment over 104 weeks in patients with moderate-to-severe psoriasis

Sustained improvement in patient-reported outcomes with continued apremilast treatment over 104 weeks in patients with moderate-to-severe psoriasis

Presenters: Chapman S1, Cirulli J2, McBride S3

Affiliations: 1Dartmouth–Hitchcock Medical Center, Lebanon, NH; 2Celgene Corporation, Summit, NJ; 3Royal Free London NHS Foundation Trust, London, UK

Background/Objective: Psoriasis is a chronic, systemic, inflammatory disease that is associated with significant impairments in quality of life (QoL), which can include physical discomfort, pruritus, and emotional distress. Apremilast is an oral, small-molecule phosphodiesterase 4 inhibitor that has demonstrated efficacy and safety versus placebo (PBO) in the LIBERATE global Phase IIIb trial in patients with moderate-to-severe plaque psoriasis. Efficacy was maintained for up to 104 weeks in patients who continued treatment with apremilast 30mg twice-daily (APR) in the LIBERATE trial. To further understand the clinical profile of APR, the effect of long-term APR treatment on patient-reported outcomes assessed at 104 weeks was evaluated in the LIBERATE patient population.

Methods: Adults 18 years of age or older with chronic plaque psoriasis for at least 12 months and who were candidates for phototherapy with no prior exposure to biologics for the treatment of psoriatic arthritis or psoriasis were included. Included patients had moderate-to-severe plaque psoriasis, as defined by Psoriasis Area and Severity Index (PASI) score 12, psoriasis-involved Body Surface Area (BSA) 10 percent, and static Physician Global Assessment (sPGA) score 3. Patients included in the study had inadequate response, inability to tolerate, or contraindication to one conventional systemic agent for the treatment of psoriasis. Patients who were excluded had prior treatment with more than three systemic agents for the management of psoriasis, other clinically significant or major uncontrolled diseases, and/or serious infections, including latent, active, or history of incompletely treated tuberculosis. LIBERATE consisted of two treatment phases: a 16-week randomized, double-blind, PBO-controlled phase and an 88-week APR extension phase for an overall treatment duration of 104 weeks. Patients were randomized (1:1:1) to PBO, APR, or etanercept 50mg once-weekly (ETN). At Week 16, all patients in the PBO and ETN groups switched to APR, and patients in the APR group continued APR. Treatment with APR was maintained from Weeks 16 to 104 (APR extension phase).

At Weeks 16 and 104, the proportion of patients achieving response, defined as the minimal clinically important difference (MCID), was evaluated for the following patient-reported outcomes: 1) Dermatology Life Quality Index (DLQI) MCID defined as an at least 5-point decrease from baseline in patients with baseline DLQI score over 5; 2) pruritus Visual Analog Scale (VAS; 0–100mm) MCID defined as an at least 20 percent decrease from baseline; 3) 36-Item Short Form Health Survey version 2 (SF-36v2) Mental and Physical Component Summary scores (MCS and PCS)–both MCIDs defined as an increase of at least 2.5 points from baseline; and 4) Patient Health Questionnaire-8 (PHQ-8)–MCID defined as achievement of score 4 (no significant depressive symptoms). Safety was assessed based on adverse events (AEs), vital signs, clinical laboratory assessments, and physical examinations. Achievement of MCID on the DLQI at Week 16 and Week 104 was a prespecified exploratory endpoint, whereas achievement of MCID on the pruritus VAS, the MCS and PCS, and the PHQ-8 were post-hoc analyses. All MCID analyses were performed using the modified intent-to-treat (mITT) population, which included all randomized patients who received one dose of study medication and had an evaluation at baseline and at the specified time point. Endpoints were analyzed using descriptive statistics, including proportions of patients achieving each endpoint by treatment group; associated 95-percent confidence intervals (CIs) were calculated. All data were analyzed as observed, with no imputation for missing values. The safety population consisted of all patients who were randomized and received one dose of study medication. Descriptive statistics were used for summaries of treatment-emergent AEs and other safety assessments.

Results: The mITT population consisted of 250 patients (PBO, n=84; APR, n=83; ETN, n=83). Patient demographics and baseline disease characteristics were generally comparable between treatment groups. The proportions of patients achieving the MCID for the MCS were generally similar among the treatment groups at Week 16. At Week 104, MCS response was maintained in PBO/APR patients and was comparable between APR/APR and ETN/APR patients at Week 104. At Week 16, the proportion of patients achieving PCS MCID was lowest in the PBO group. At Week 104, PCS response was comparable between the APR/APR and ETN/APR groups and remained lower in the PBO/APR group.

At Week 16 and Week 104, proportions of patients achieving the MCID for PHQ-8 (i.e., score 4 [no significant depressive symptoms]) were generally similar among the treatment groups; response was maintained at Week 104 in the APR/APR group and in patients who switched at Week 16 from ETN or PBO to APR. During the PBO-controlled period (Weeks 0 to 16), AEs occurring in five percent of patients in any treatment group were diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, headache, and tension headache. During the APR extension phase (Weeks 16–104), AEs that occurred in five percent of patients in any treatment group included those observed during the PBO-controlled period as well as arthralgia, rebound psoriasis, pain in extremity, bronchitis, psoriasis, and sinusitis. Most AEs were mild or moderate in severity, did not increase with prolonged APR exposure, and did not lead to study discontinuation. No clinically meaningful changes were reported in laboratory parameters. No cases of tuberculosis (new or reactivation) were reported during the trial.

Conclusion: In biologic-naive patients with moderate-to-severe psoriasis, improvements in patient-reported outcomes, including QOL and pruritus, were generally maintained with continued APR treatment up to 104 weeks. AEs were consistent with the known safety profile of APR.

Funding/Dislcosures: The authors acknowledge financial support for this study from Celgene Corporation. Joshua Cirulli is an employee of the Celgene Corporation.

A randomized, multicenter, double-blind, placebo-controlled Phase II clinical trial of serlopitant for the treatment of chronic pruritus

A randomized, multicenter, double-blind, placebo-controlled Phase II clinical trial of serlopitant for the treatment of chronic pruritus

Presenters: Ständer S1, Yosipovitch G2, Kerby MB3, Larrick JW4, Perlman AJ4, Schnipper EF4, Zhang X3, Tang JY5, Luger TA2, Steinhoff M6,7

Affiliation: 1Center for Chronic Pruritus, Department of Dermatology, University Hospital Münster, Münster, Germany; 2Miami Itch Center, Department of Dermatology and Cutaneous Surgery Miller School of Medicine, University of Miami, Miami, FL; 3Menlo Therapeutics Inc, Redwood City, CA; 4Velocity Pharmaceutical Development, LLC, San Francisco, CA, USA; 5Department of Clinical Dermatology, Stanford University, Stanford, CA; 6Department of Dermatology and UCD Charles Institute of Translational Dermatology, University College Dublin, Dublin, Ireland; 7Department of Dermatology, University of California San Diego, San Diego, CA

Background/Objective: Chronic pruritus, a common debilitating symptom of many conditions, can result in significant morbidity and impaired quality of life. Inadequate itch relief or undesirable safety and tolerability issues have been associated with many of the current therapies. The neuropeptide substance P and its receptor neurokinin 1 receptor (NK1R) play important roles in pruritus signaling. The potent, highly selective, brain-permeable, oral NK1R antagonist serlopitant is currently under investigation for the treatment of chronic pruritus and other conditions. Here, we report the efficacy and safety results from a Phase II clinical trial of once-daily oral serlopitant versus placebo for the treatment of chronic pruritus (ClinicalTrials.gov ID, NCT01951274).

Methods: Key eligibility criteria included pruritus lasting at least six weeks that was nonresponsive or inadequately responsive to treatment with topical steroids or antihistamines and a baseline Visual Analog Scale (VAS) pruritus score of at least 7cm. Patients were randomized 1:1:1:1 to receive serlopitant 0.25mg, 1mg, 5mg, or placebo. After a loading dose of three tablets at baseline, patients took one tablet daily at bedtime for six weeks. The primary efficacy endpoint was the VAS pruritus score percentage change from baseline. Secondary pruritus measures included the Numeric Rating Scale (NRS), Subject’s Global Assessment of itch, patient responses to the Dermatology Life Quality Index and Pittsburgh Sleep Symptom Questionnaire- Insomnia questionnaires, and the Physician’s Global Assessment. Adverse events (AEs) and clinical and laboratory assessments were evaluated during treatment and follow-up. Change from baseline itch intensity as measured by the VAS and NRS score was analyzed in the intent-to-treat population, and the difference in average change from baseline between the serlopitant and placebo groups was tested using a t-test without control for multiplicity. Primary and secondary efficacy endpoints used an alpha value of p<0.05.

Results: A total of 257 patients were randomized to serlopitant 0.25mg (n=64), 1mg (n=65), or 5mg (n=64) or placebo (n=64); baseline characteristics were comparable between groups. Differences in percentage change from baseline itch VAS score were statistically significantly greater with serlopitant versus placebo for serlopitant 1mg at Weeks 3, 4, 5, and 6 and 5mg at Weeks 4, 5, and 6. Statistically significant improvements in severity of itch from baseline were also demonstrated using the NRS with serlopitant 1mg and 5mg at Weeks 4, 5, and 6 (p?0.05) compared with placebo. The most common treatment-emergent adverse events (TEAEs) in the serlopitant groups were somnolence (1.6%, 4.6%, and 4.7% for serlopitant 0.25mg, 1mg, and 5mg, respectively, and 1.6% for placebo) and diarrhea (0%, 6.2%, and 3.1% for serlopitant 0.25mg, 1mg, and 5mg, respectively, and 1.6% for placebo). Most TEAEs were of mild or moderate intensity. There were no meaningful trends in laboratory abnormalities or changes in vital signs, and no deaths.

Conclusion: Serlopitant 1mg and 5mg provided statistically significant reductions in pruritus intensity compared with placebo. Serlopitant was well tolerated. Almost all TEAEs were of mild or moderate intensity, and no meaningful adverse safety trends were observed in this study.

Burden of axillary hyperhidrosis using a patient-reported outcome measure to assess impact on activities and bothersomeness

Burden of axillary hyperhidrosis using a patient-reported outcome measure to assess impact on activities and bothersomeness

Presenters: Pariser DM1, Hebert AA2, Drew J3, Quiring J4, Glaser DA5

Affiliations: 1Eastern Virginia Medical School and Virginial Clinical Research, Inc., Norfolk, VA; 2UTHealth McGovern Medical School, Houston, TX; 3Dermira, Inc., Menlo Park, CA; 4QST Consultations, Allendale, MI; 5Saint Louis University, St. Louis, MO

Introduction: Hyperhidrosis affects approximately 4.8 percent of the United States population, and approximately three-quarters of patients experience a negative psychological impact. Anxiety and depression are over 3.5 times more common among hyperhidrosis sufferers. The Axillary Hyperhidrosis Patient Measures (AHPM)­—the four-item Axillary Sweating Daily Diary (ASDD), two-item, child-specific version of ASDD [ASDD-C] for patients at least nine years old but less than 16 years old, six Weekly Impact (WI) items, and single-item Patient Global Impression of Change (PGIC)—were developed in consultation with the United States Food and Drug Administration (FDA) and in consideration of FDA patient-reported outcomes (PRO) guidance. Baseline values from two Phase III trials of an investigational axillary hyperhidrosis treatment, topical glycopyrronium tosylate (GT; formerly DRM04), were evaluated to characterize the burden of disease.

Methods: ATMOS 1 (DRM04-HH04, NCT02530281) and ATMOS 2 (DRM04 HH05, NCT02530294) were randomized, double-blind Phase III trials. Patients at least nine years of age with primary axillary hyperhidrosis for at least six months, gravimetrically measured sweat production of at least 50mg per five minutes in each axilla, ASDD axillary sweating severity item (Item 2) 4 or above (numeric rating scale 0 to 10), and Hyperhidrosis Disease Severity Scale (HDSS) Grade 3 or above were randomized 2:1 to GT or vehicle applied once-daily to each axilla for 28 days. Item 1 assessed the presence of underarm sweating and acted as a gatekeeper question for Item 2. ASDD Items 3 and 4 assessed impact and bother of axillary sweating (numeric rating scale 0–4). WI Items assessed the impact of axillary sweating (needing to change shirt during the day, needing to bathe at least once a day, feeling less confident, feeling embarrassed, avoiding interactions, kept from doing an activity on a weekly basis). ASDD items were scored as a weekly average of daily responses. Baseline ASDD item scores and proportion of patients with positive responses to WI items are reported.

Results: Among 697 randomized patients, 665 were at least 16 years of age and were asked Items 3 and 4 and WI items. For ASDD Item 2, 59.3 percent and 59.8 percent of patients had a score of 7 or above (moderately severe sweating) at baseline in ATMOS-1 and ATMOS-2, respectively. For Item 3, 69.4 percent and 71.7 percent had a score of 2 (moderate impact) or above. For Item 4, 77.8 percent and 77.4 percent had a score of 2 (moderate bother) or above. In both studies, a majority of patients reported being impacted by their excess sweating, with most having to avoid interactions or take additional measures (e.g., bathing more than once a day, changing shirts during the day) due to excessive sweating. Over 96 percent of patients experienced embarrassment due to underarm sweating.

Conclusion: In this analysis, over 69 percent and 77 percent of patients reported feeling moderately impacted and bothered by their axillary hyperhidrosis during daily activities at baseline. Nearly all patients (>96%) reported embarrassment, underscoring previously reported negative psychological impact of this underreported and underdiagnosed condition.

Open-label study (ARIDO) evaluating long-term safety of topical glycopyrronium tosylate (GT) in patients with primary axillary hyperhidrosis

Open-label study (ARIDO) evaluating long-term safety of topical glycopyrronium tosylate (GT) in patients with primary axillary hyperhidrosis

Presenters: Glaser DA1, Hebert AA2, Nast A3, Werschler WP4, Shideler S5, Green L6, Mamelok RD7, Drew J8, Quiring J9, Pariser DM10

Affiliations: 1Saint Louis University, St. Louis, MO; 2UTHealth McGovern Medical School, Houston, TX; 3Charité–Universitätsmedizin Berlin, Berlin, Germany; 4Premier Clinical Research, Spokane, WA; 5Shideler Dermatology and Skin Care Center, Carmel, IN; 6George Washington University School of Medicine, Washington, DC; 7Mamelok Consulting, Palo Alto, CA; 8Dermira, Inc., Menlo Park, CA;

9QST Consultations, Allendale, MI; 10Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA

Background/Objective: Hyperhidrosis affects an estimated 4.8 percent of the United States population, or approximately 15.3 million people, and the impact of hyperhidrosis on quality of life is reported as comparable to or greater than psoriasis or eczema. Glycopyrronium tosylate (GT; formerly DRM04) is a topical cholinergic receptor antagonist being developed for the treatment of primary axillary hyperhidrosis in patients nine years of age or older. GT has been assessed in two replicate, randomized, double-blind, vehicle?controlled, pivotal Phase III lead-in trials (ATMOS-1 and ATMOS?2). GT was generally well tolerated and demonstrated clinically meaningful improvements in disease severity and reductions in sweat production through four weeks in these trials. ARIDO (NCT02553798) assessed the long-term safety of GT in a minimum of 100 patients with primary axillary hyperhidrosis treated for at least 12 months.

Methods: ARIDO was a 44-week, open-label extension of ATMOS-1 (NCT02530281) and ATMOS-2 (NCT02530294). In ATMOS-1/ATMOS-2, patients with primary axillary hyperhidrosis were randomized 2:1 to GT (3.75% topical solution) or vehicle applied once daily to each axilla for 28 days (Figure 1). Patients who completed ATMOS-1/ATMOS-2 with at least 80-percent treatment adherence were eligible to continue onto ARIDO and receive open-label GT for up to 44 weeks or until early termination, including patients terminated once the study objective of 100 patients receiving treatment for at least 12 months was achieved. Subjects included in ATMOS-1/ATMOS-2 were at least nine years of age (patients older than 16 were recruited only at US sites), had primary axillary hyperhidrosis for at least six months, showed gravimetrically measured sweat production of at least 50mg per five minutes in each axilla. Included subjects scored a 4 or above on Item 2 (0–10 numeric rating scale) of the Axillary Sweating Daily Diary (ASDD; for patients 16 years of age or older) or ASDD?Children (ASDD-C; for patients under 16 years of age) and 3 or above on the Hyperhidrosis Disease Severity Scale (HDSS). Exclusion criteria included history of a condition that could cause secondary hyperhidrosis; prior surgical procedure or treatment with a medical device for axillary hyperhidrosis, treatment with iontophoresis within four weeks or treatment with botulinum toxin within one year for axillary hyperhidrosis; axillary use of nonprescription antiperspirants within one week or prescription antiperspirants within two weeks; new or modified psychotherapeutic medication regimen within two weeks; treatment with medications having systemic anticholinergic activity, centrally acting alpha-2 adrenergic agonists, or beta-blockers within four weeks (unless dose had been stable for at least four months with no anticipated change); and conditions that could be exacerbated by study medication.

Results: The majority of patients (86.6%; N=564) completing ATMOS-1/ATMOS-2 (369 patients [65.4%] had received GT, and 195 [34.6%] had received vehicle) continued into ARIDO. Of the patients enrolled in ARIDO, most patients were female (55.3%) and Caucasian (83.3%) with a mean age of 33.0 years and mean body mass index (BMI) of 27.3kg/m2. The trial was terminated, per protocol, once study objectives were reached. A total of 226 patients completed 44 weeks of treatment. Through Week 44/ET in ARIDO (up to 48 weeks of GT), GT?treated patients continued to demonstrate improvements in efficacy measures, including sweat production and HDSS responder rate. From baseline in ATMOS-1/ATMOS-2 to Week 44/ET in ARIDO, mean sweat production decreased by 95.7±140.8mg per five minutes, which was maintained from a decrease of 107.6±207.2mg per five minutes in GT?treated patients after four weeks in ATMOS-1/ATMOS-2. At Week 44/ET in ARIDO, HDSS responder rate (?2-grade improvement) was 63.2 percent, a further improvement from 59.1 percent in GT-treated patients at Week 4 in ATMOS-1/ATMOS-2. HDSS grade improved by 1, 2, and 3 grades in 30.9 percent, 46.7 percent, and 16.5 percent of patients, respectively. After 44 weeks, 329 (59.8%) patients reported at least one treatment-emergent adverse event (TEAE), though most were mild or moderate in severity. Most common TEAEs were dry mouth, blurred vision, application site pain, nasopharyngitis, and mydriasis. A total of 44 (8.0%) patients discontinued due to a TEAE and 7 (1.3%) reported at least one serious TEAE. Prespecified anticholinergic TEAEs of interest were reported in 78 (14.2%) patients; most were mild or moderate in severity and were able to be managed by dose interruption. Thirty-seven patients reported 45 vision blurred events; 40 (88.9%) were bilateral. Twenty-nine patients reported 37 mydriasis events; 31 (83.8%) were unilateral.

Conclusion: Safety results were consistent with anticholinergic treatment and with the safety profile observed in prior GT studies, with no new or unexpected findings. Most TEAEs were mild or moderate in severity and considered by the

Investigator to be related to study drug. A low number of subjects discontinued due to a TEAE. While approximately one-third of patients reported local skin reactions, most were mild or moderate in severity. Incidence of TEAEs, including prespecified anticholinergic TEAEs of interest, did not increase with long-term treatment. Efficacy measures obtained at the end of treatment in ARIDO indicated that subjects had maintained sweat production reduction and less bothersome sweating compared with baseline in ATMOS-1/ ATMOS-2. GT was generally well tolerated, and improvements in efficacy measures were maintained in patients with primary axillary hyperhidrosis when applied once-daily to both axillae over a maximum of 48 weeks.

Funding/Disclosures: This study was funded by Dermira, Inc. Medical writing support was provided by Prescott Medical Communications Group (Chicago, IL). Dee Anna Glaser is a consultant and investigator for Dermira, Inc. Adelaide A. Herbert is a consultant for Dermira, Inc. and employee of the University of Texas Medical School, Houston, which received compensation from Dermira, Inc. for study participation. Alexander Nast is an employee of Charité – Universitätsmedizin Berlin, which received compensation from Dermira, Inc. for study participation. William P. Werschler is a consultant and investigator for Dermira, Inc. Stephen Shideler is an investigator for Dermira, Inc. Lawrence Green is a consultant and investigator for Dermira, Inc. and an investigator for Brickell. Richard D. Mamelok is a consultant for Dermira, Inc. Janice Drew is an employee of Dermira, Inc. John Quiring is an employee of QST Consultations. David M. Pariser is a consultant and investigator for Dermira, Inc.

Confirmatory psychometric evaluation of the axillary sweating daily diary: a validated patient-reported outcome measure to assess axillary hyperhidrosis sweating severity

Confirmatory psychometric evaluation of the axillary sweating daily diary: a validated patient-reported outcome measure to assess axillary hyperhidrosis sweating severity

Presenters: Glaser DA1,1 Hebert AA2, Fehnel S3, DiBenedetti D3, Nelson L3, Drew J4, Pariser DM5

Affiliations: 1Saint Louis University, St. Louis, MO; 2UTHealth McGovern Medical School at Houston, Houston, TX; 3RTI Health Solutions, Research Triangle Park, NC; 4Dermira, Inc., Menlo Park, CA; 5Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA

Background/Objective: Hyperhidrosis affects an estimated 4.8 percent of the United States population; approximately three-quarters of patients experience negative psychological effects, with anxiety and depression occurring over

3.5?times more frequently in people with hyperhidrosis than in people without it. Despite high prevalence and burden of disease, few disease-specific outcome measures are available. The Hyperhidrosis Disease Severity Scale (HDSS) is widely used in clinical studies and well understood in clinical practice; however, it does not conform to current regulatory standards for patient-reported outcome (PRO) measures used to support product approvals and labeling. The four-item Axillary Sweating Daily Diary (ASDD) and a child-specific two?item version (ASDD-C) for use in patients between 9 and 16 years of age were developed according to current regulatory standards. The ASDD/ASDD-C axillary sweating severity item (Item 2) was specifically developed for use as an endpoint in clinical trials in support of approval and labeling (and also as a useful clinical parameter). In addition to the ASDD, patients 16 years of age or younger were asked to complete six Weekly Impact Items designed to assess the impact and bother of hyperhidrosis on daily activities and a single?item Patient Global Impression of Change (PGIC) to assess overall change in sweating severity. Initial psychometric evaluation of the ASDD was conducted using data from a Phase II study of topical glycopyrronium tosylate (GT; formerly DRM04), an investigational treatment for primary axillary hyperhidrosis in patients nine years of age or older; results have been previously reported and provide preliminary support for the use of this measure to evaluate the efficacy of axillary hyperhidrosis treatment in clinical trials. In this study, we aimed to confirm and extend the psychometric evidence supporting ASDD/ASDD-C axillary sweating severity item (Item 2) based on pooled data from two Phase III clinical trials of GT: ATMOS-1

(DRM04-HH04; NCT02530281) and ATMOS-2 (DRM04-HH05; NCT02530294)

Methods: ATMOS-1 and ATMOS-2 were Phase III, multicenter (ATMOS-1: sites in the United States and Germany; ATMOS-2: sites in United States), parallel-group, four-week, double-blind clinical trials in which patients with primary axillary hyperhidrosis were randomized (2:1) to GT or vehicle. Eligible patients were at least nine years of age (patients <16 years were only recruited at United States sites) and had primary axillary hyperhidrosis for at least six months, with gravimetrically measured sweat production of at least 50mg per five minutes in each axilla, ASDD/ASDD-C axillary sweating severity item (Item 2) score 4 or above, and Hyperhidrosis Disease Severity Scale (HDSS) Grade 3 or 4. ASDD/ASDD-C Item 2 responses and sweat production were assessed in two age groups (?9 years and ?16 years). ASDD/ASDD-C items were scored as a weekly average of daily responses; at least four days of daily data were required for analysis. Weekly Impact Items and PGIC were included to evaluate construct validity. Potential floor and ceiling effects and nonresponse bias were evaluated based on both summary statistics and graphical techniques. Test-retest reliability was evaluated through the computation of intraclass correlation coefficients (ICCs) between Week 3 and Week 4; a value of at least 0.70 was considered acceptable. Construct validity was evaluated at Week 4 based on correlations between ASDD/ASDD-C Item 2 and ASDD items related to the impact and bother of sweating (Items 3 and 4, respectively), HDSS, sweat production, and other PRO measures, as available. All statistical tests were two-tailed using a type I error rate of one percent (?=0.01).

Results. The pooled Phase III study population (n=697) included 665 patients who were at least 16 years of age and 32 patients aged 9 to 15 years of age. The response distribution for the ASDD/ASDD-C axillary sweating severity item (Item 2) demonstrated no floor or ceiling effect and no nonresponse bias. Construct validity was supported by strong correlations between ASDD Item 2 and the ASDD items addressing the impact and bother of axillary sweating (Items 3 and 4, respectively).

Test-retest reliability was supported by ICCs of 0.93 for both age subgroups, which is well above the 0.70 criterion and within the confidence interval (CI) of the Phase II estimate of 0.91 (95% CI: 0.87, 0.94. The ASDD/ASDD-C Item 2 responsiveness, or ability to detect change in sweating severity, was demonstrated by large effect sizes and correlations that were within the expected range for the change in ASDD/ASDD-C Item 2 and the change in the gravimetric measures of sweat production.

Conclusion: The current study confirms and extends the psychometric evidence supporting the

ASDD/ASDD?C as a new PRO measure developed according to current regulatory standards. The psychometric findings presented here continue to support use of the ASDD/ASDD-C axillary sweating severity item (Item 2) as an endpoint in assessing the efficacy of treatments for patients with axillary hyperhidrosis.

Funding/Disclosures: This study was funded by Dermira, Inc. Dee Anna Glaser is a consultant and investigator for Dermira, Inc. Adelaide A. Herbert is a consultant for Dermira, Inc. and employee of the University of Texas Medical School, Houston, which received compensation from Dermira, Inc. for study participation. Dana DiBenedetti, Lauren Nelson, and Sheri Fehnel are employees of RTI Health Solutions. Janice Drew is an employee of Dermira, Inc. David M. Pariser is a consultant and investigator for Dermira, Inc.

Perceptions regarding use of anti-tumor necrosis factor treatments for women of childbearing age among healthcare professionals

Perceptions regarding use of anti-tumor necrosis factor treatments for women of childbearing age among healthcare professionals

Presenters: Voorhees AV1, Afzali A2, Schwartzman S3, Ecoffet C4, Pisenti L5, Stark J5, Yassine M5, Abraham B6

Affiliations: 1Eastern Virginia Medical School, Norfolk, VA; 2The Ohio State University Wexner Medical Center, Columbus, OH; 3Hospital for Special Surgery, New York, NY; 4UCB Pharma, Brussels, Belgium; 5UCB Pharma, Smyrna, GA; 6Houston Methodist Hospital, Houston, TX

Background/Objective: For women with chronic inflammatory diseases (e.g., psoriasis, psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, inflammatory bowel disease), disease onset, diagnosis, and treatment initiation often overlap with peak reproductive years. High disease activity is associated with increased risk of pregnancy complications and adverse outcomes, and achieving disease control is therefore an important goal for the success of these pregnancies. Tumor necrosis factor antagonists (anti-TNFs) are effective treatments, but use among women of childbearing age (WoCBA) varies due to differing attitudes regarding their safety profiles versus benefits. This survey aimed to better understand perceptions and attitudes of healthcare professionals (HCPs) across different specialties regarding treatment of WoCBA patients with anti-TNFs during pregnancy and lactation.

Methods: An online survey was conducted in the United States on July 6, 2017, by SERMO RealTime. WoCBA was defined as women between the ages of 18 and 45 years. Survey participants included dermatologists (DM), gastroenterologists (GI), rheumatologists (RA) and obstetricians/gynecologists (OB).

Results: Two-hundred and fifty-six HCPs participated in the survey, including 53 DMs, 50 GIs, 50 RAs, 50 OBs. Half of the female patient population across specialties were WoCBA. DMs had the lowest proportion (27%) of female patients prescribed anti-TNFs (GI: 31%; RA: 43%). While physicians indicated being comfortable prescribing anti-TNFs for WoCBA patients, concerns were more prevalent once patients actively started family planning. DMs (57%) and OBs (62%) were more likely to recommend discontinuation of anti-TNFs before conception than GIs (36%) and RAs (46%); 45 percent of DMs and 54 percent of OBs agreed that WoCBA patients should stop anti-TNFs once they are pregnant (compared to <35% GIs and RAs). GIs (46%) and RAs (42%) agreed more strongly than DMs (15%) and OB (20%)on making disease control during pregnancy their priority . Only 17 percent of DMs felt that disease control reduces the risk of pregnancy complications and adverse outcomes, compared to GIs (52%), RAs (42%) and OBs (28%). More DMs and OBs than GIs and RAs believed patients who are breastfeeding should not take anti-TNFs, although a high degree of uncertainty was indicated. Overall, HCPs believed that more safety data during and after pregnancy are needed to feel more comfortable with prescribing anti-TNFs to WoCBA patients who are or might become pregnant in the future.

Conclusion: Our survey demonstrates the variability in clinical management of women with inflammatory or autoimmune diseases. Uncertainty about risks of anti-TNF use during pregnancy and lactation is common. Further research and multidisciplinary engagement among HCPs are needed to discuss and safely treat WoCBA.

Fundings/Disclosures: AVV: Consultant for: Dermira, Novartis, Celgene, AbbVie; board member: Dermira, Novartis, Celgene, AbbVie, Allergan, Derm Tech, Valeant, WebMD; ex-spouse pension: Merck; AA: Consultant for AbbVie, Takeda, UCB Pharma, research grant support from AbbVie, non-profit consultant and board member for IBD Horizons; SS: Consultant for Abbvie, Antares, Genentech, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sanofi, UCB Pharma; speaker fees: Abbvie, Janssen, Genentech, Pfizer, UCB Pharma, Crescendo, Novartis; board member: Crescendo Biosciences, Discus Analytics, National Psoriasis Foundation; CE, LP, JS, MY: Employee of UCB Pharma; MC: Employee of Dermira Inc; BA: Grant/research support: Janssen, UCB Pharma; speaker’s fees: AbbVie, American Reagent, Janssen, UCB Pharma

Long-term results of investigator-assessed efficacy and safety of 200mg dose of sonidegib for locally advanced basal cell carcinoma: 30-month BOLT analysis

Long-term results of investigator-assessed efficacy and safety of 200mg dose of sonidegib for locally advanced basal cell carcinoma: 30-month BOLT analysis

Presenters: Migden M1, Lewis KD2

Affiliations: 1University of Texas MD Anderson Cancer Center, Departments of Dermatology, Division of Internal Medicine, and Head and Neck Surgery, Division of Surgery, Houston, TX; 2University of Colorado Denver, School of Medicine, Division of Medical Oncology, Denver, CO

Background/Objective: The 200mg dose of sonidegib was approved in 2015 in the European Union, Switzerland, Australia, and the United States for the treatment of patients with locally advanced basal cell carcinoma (laBCC) who are not amenable to curative surgery or radiation therapy. In both Switzerland and Australia, sonidegib is also approved for the treatment of metastatic BCC (mBCC). Sonidegib is a selective smoothened (SMO) inhibitor that blocks hedgehog pathway signaling. Approvals were based on results from the pivotal BOLT Phase II clinical trial (NCT01327053). Efficacy and safety data from BOLT were assessed by both investigator and central review. Here, we report the investigator-assessed efficacy and safety data of sonidegib 200mg QD from the 30-month analysis.

Methods: BOLT is a randomized, double-blind clinical trial that was conducted in 58 centers across 12 countries. Patients received either 200mg or 800mg of sonidegib once daily. Only the 200mg dose data will be presented here, as this dose was found in earlier studies to be more tolerable and equally as effective as the higher dose. As a primary endpoint, investigators evaluated objective response rate (ORR), which is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor evaluations were done using BCC-modified Response Evaluation Criteria In Solid Tumors (mRECIST) for laBCC. Sonidegib safety was monitored, including the monitoring of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.

Results: In patients with laBCC who received sonidegib 200mg (n=66), the investigator-assessed ORR was 71 percent. Median overall survival was not reached at this time point, but the two-year overall survival rate was 93 percent. Tumor responses were durable with a median duration of response of 15.7 months. At the 30-month data cutoff, the median duration of PFS was 19.4 months. One death was reported in the 200mg dose arm of patients with laBCC, but it was not considered to be related to study treatment. The safety profile of sonidegib 200mg was manageable, and no new safety concerns were found compared to the earlier BOLT data analyses. In summary, 43 percent of patients experienced grade 3/4 adverse events and AEs requiring dose interruptions/reductions. AEs that led to discontinuation occurred in 30 percent of patients, and the most commonly reported AEs included muscle spasms (56%), alopecia (52%), and dysgeusia (47%).

Conclusion: In the BOLT 30-month analysis, sonidegib 200mg QD provided sustained efficacy and a continued long-term acceptable safety profile in patients with laBCC. Interestingly, both the median DOR and median PFS data were higher when assessed by central review compared to investigator review. Given the stringent criteria used to assess tumor responses in the BOLT trial, these data support the use of sonidegib 200mg QD in patients with laBCC when used according to local treatment guidelines.

Safety and efficacy of A-101 hydrogen peroxide topical solution 40% in adults with seborrheic keratosis: results from the Phase III, randomized, double-blind, vehicle-controlled, parallel-group study

Safety and efficacy of A-101 hydrogen peroxide topical solution 40% in adults with seborrheic keratosis: results from the Phase III, randomized, double-blind, vehicle-controlled, parallel-group study

Presenters: Draelos ZD1, Kempers SE2, Smith SR3, Wilson DC4; Powala C5, Bradshaw M6; Estes E5; Shanler S5

Affiliations: 1Dermatology Consulting Services, High Point, NC; 2Minnesota Clinical Study Center, Fridley, MN; 3California Dermatology & Clinical Research Institute, Encinitas, CA; 4The Education and Research Foundation, Inc., Lynchburg, VA; 5Aclaris Therapeutics, Malvern, PA

Objective: Seborrheic keratosis (SK) is one of the most common benign skin lesions, affecting over 80 million Americans, yet there is no United States Food and Drug Administration (FDA)-approved treatment available. The purpose of this study was to evaluate the safety and efficacy of a proprietary 40% hydrogen peroxide topical solution (A-101) versus its matching vehicle for the treatment of seborrheic keratosis.

Design: Adults with four eligible SK lesions identified by the study investigator were randomized 1:1 to A-101 or a matching A-101 vehicle. Eligible lesions were stable, typical SKs, measuring 5 to 15mm in both width and length and less than 2mm in thickness. Subjects were required to present with at least one lesion on the trunk or extremities and at least one lesion on the face. All treatments were performed by a non- physician sub-investigator to maintain blinding. All lesions were treated on Day 1. Previously treated SK lesions with a Physician’s Lesion Assessment score over 0 were re-treated on Day 22 (PLA scale: 0=clear, 1=near clear, 2=thickness ?1mm, and 3=thickness>1mm). At Day 106, the investigator assessed the lesions using the validated PLA scale.

Results: Total of 450 subjects were enrolled. At Day 106, significantly more subjects receiving A-101 (intent-to-treat ITT population) completely cleared (PLA=0) all four lesions (4% vs. 0%, P<0 .002) and 3 of 4 lesions (13.5% vs. 0%, P<0.0001) versus vehicle in the primary and secondary endpoints, respectively. In the a priori exploratory analyses (per protocol population [PPP], n=439), significantly higher mean per-subject percentage of lesions achieving clear or near clear (PLA?1) was observed in the A-101 arm (47.5% vs. 10.2%; P<0.0001). Significantly higher mean per-subject percentage of facial lesions achieving clear or near clear (PLA?1) was also observed (64.4% vs.15.0% at Day 106; P<.0001). Adverse events were comparable between groups.

Local skin reactions were predominantly mild and generally resolved by Day 106. At all visits, atrophy, erosion, hypopigmentation, scarring, or ulceration were reported for at least four percent of lesions.

Conclusion: A-101, a 40% hydrogen peroxide topical solution, is a safe, effective, and well-tolerated treatment for SK. If approved, it would offer the first FDA-approved topical treatment for SK.