Atopic Dermatitis

May 21, 2018

Regeneron Pharmaceuticals and Sanofi announced that a pivotal Phase III trial evaluating DUPIXENT (dupilumab) to treat moderate-to-severe atopic dermatitis met its primary and key secondary endpoints. In the trial, treatment with DUPIXENT as monotherapy significantly improved measures of overall disease severity, skin clearing, itching and certain health-related quality of life measures. The pivotal, Phase III, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of DUPIXENT monotherapy in adolescent patients with moderate-to-severe atopic dermatitis. The trial enrolled 251 patients who were 12 years to 17 years of age with moderate-to-severe atopic dermatitis whose disease could not be adequately controlled with topical medications or for whom topical treatment was medically inadvisable. In total, 92 percent of these patients suffered from at least one concurrent allergic condition such as allergic rhinitis, asthma or food allergy. The primary endpoints were the proportion of patients achieving Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and 75 percent improvement in Eczema Area and Severity Index (EASI-75, co-primary endpoint outside of the U.S.). Results showed 24 percent of patients who received weight-based dosing of DUPIXENT every two weeks (200 mg or 300 mg) and percent of patients who received a fixed dose of DUPIXENT every four weeks (300 mg) achieved the primary endpoint - clear or almost clear skin (IGA; score of 0 or 1) - compared with 2 percent with placebo (p less than 0.0001, and p=0.0007, respectively). Patients treated with DUPIXENT had significant improvement in disease severity at 16 weeks.

May 7, 2018

Galapagos and MorphoSys announced that the first patient has been screened in IGUANA, a Phase II study with MOR106, an investigational antibody directed against IL-17C, in atopic dermatitis patients. At least 180 patients with moderate-to-severe atopic dermatitis (AD) are planned to be treated over a 12- week period with one of three different doses of MOR106 (1, 3 or 10 mg/kg) or placebo using two different dosing regimens in this Phase II trial in multiple centers across Europe. The placebo-controlled, double-blind study will evaluate the efficacy, safety and pharmacokinetics (PK) of MOR106. Dosing at two- or four-week intervals will be evaluated over the 12-week treatment period, followed by a 16-week observation period. The primary objective will be assessed by the percentage change from baseline in Eczema Area and Severity Index (EASI) score at week 12.

February 26, 2018

AbbVie presented new positive results from a Phase II dose-ranging study evaluating upadacitinib, an investigational, once-daily oral JAK1-selective inhibitor, in adult patients with moderate to severe atopic dermatitis. This dose-ranging study is an ongoing 88-week Phase II, randomized, double-blind, parallel-group, placebo-controlled multicenter study designed to evaluate the safety and efficacy of upadacitinib in adult patients with moderate to severe atopic dermatitis. In Period 1, subjects were randomized in a 1:1:1:1 ratio to one of four treatment for 16 weeks. At week two of treatment with upadacitinib showed all dose groups (30/15/7.5 mg once-daily) achieved significant improvement in extent and severity of atopic dermatitis. Secondary endpoints included a proportion of patients achieving EASI 90, EASI 75, an Investigator Global Assessment (IGA) of 0 or 1 and percent change in pruritus/itch numerical rating scale from day one to week 16 in comparison with placebo.

March 13, 2017

Regeneron Pharmaceuticals and Sanofi reported results of a phase III study of DUPIXENT with topical corticosteroids (TCS) for uncontrolled moderate to severe atopic dermatitis (AD). In the one year study, patients were randomized to receive DUPIXENT 300mg weekly with TCS, DUPIXENT 300mg every two weeks with TCS or placebo with TCS. DUPIXENT with TCS significantly improved measures of overall disease severity at 16 and 52 weeks when compared to placebo with TCS. At 52 weeks, 40% of patients who received DUPIXENT 300mg weekly with TCS, and 36% of patients who received DUPIXENT 300mg every two weeks with TCS achieved clear or almost clear skin (IGA zero or one), compared to 12.5% of patients receiving placebo with TCS (p<0.0001). At 52 weeks, 64% of patients who received DUPIXENT 300mg weekly with TCS, and 65% of patients who received DUPIXENT 300mg every two weeks with TCS achieved EASI-75, a 75% reduction on an index measuring eczema severity, compared to 22% with placebo with TCS (p<0.0001). At 52 weeks, the mean percent improvement from baseline in the intensity of patient-reported itch, as measured by the Pruritus Numerical Rating Scale (NRS), was 54% for patients who received DUPIXENT weekly with TCS and 56% for patients who received DUPIXENT every two weeks with TCS, compared to 27% for patients receiving placebo with TCS (p<0.0001).At 52 weeks, the mean percent improvement in EASI from baseline was 80% for patients who received DUPIXENT weekly with TCS and 78% for patients who received DUPIXENT every two weeks with TCS, compared to 46% for patients receiving placebo with TCS (p<0.0001). The DUPIXENT Biologics License Application (BLA) was accepted for Priority Review by the FDA with a target action date of March 29, 2017. The FDA granted DUPIXENT Breakthrough Therapy designation in uncontrolled moderate to severe AD in 2014. The EMA accepted for review the Marketing Authorization Application (MAA) on December 8, 2016.The EMA and FDA have conditionally accepted DUPIXENT as the trade name for dupilumab. 

March 7, 2016

Santalis Pharmaceuticals has released results of Santalia AD product regimen in a single-center, open-label study enrolling 25 patients, ages 3 months to 12 years with mild, moderate or severe atopic dermatitis with a mean beginning Eczema Area and Severity Index (EASI) score of 11.1 (moderate). Treatable atopic dermatitis, for this study, was defined as an EASI score ≥5 but ≤52. The EASI scoring system is a validated investigator-assessed instrument, which measures the severity of clinical attributes of atopic dermatitis in patients. Patients (or their caregivers) were instructed to apply the Santalia AD Regimen cleanser and cream twice daily for 60 days and bubble bath at least three times weekly. 22 out of 25 patients completed the study. 82% (18/22) of patients met the primary efficacy endpoint (a 25% reduction in their EASI score). 91% (20/22) of patients experienced a reduction in their EASI score. 68% of patients achieved an IGA score of “much improved” or “very much improved” with a minimum two-grade improvement after eight weeks of treatment. 61.9% of patients achieved an IGA score of “much improved” or “very much improved” with a minimum two-grade improvement after four weeks of treatment. Patients demonstrated an average 60% reduction in EASI score over baseline. In patient diary responses, the aggregate score for all diary responses went from zero at study commencement to 3.1 (much improvement) in eight weeks. 74.7% of respondents reported an aggregate score of three (much improvement) or four (very much improved) at study end. 78.9% reported a reduction in both redness and an improvement in skin texture of the treated area and 73.7% reported an improvement in pain or irritation of the treatment area. 

July 20, 2015

Anacor Pharmaceuticals reported results of two phase III studies of Crisaborole Topical Ointment, 2% (formerly AN2728) in development for the potential treatment of mild-to-moderate atopic dermatitis in children and adults. The studies were multicenter, double-blind, vehicle-controlled studies of over 750 patients each, aged 2 years and older with mild-to-moderate atopic dermatitis (defined as an Investigator’s Static Global Assessment (ISGA) score of two (mild) or three (moderate)). The ISGA is a five-point scale ranging from zero (clear) to four (severe). Patients were randomized in a 2:1 ratio (crisaborole:vehicle). Crisaborole or vehicle was applied twice daily for 28 days. Time to Success in ISGA: Time course to success in ISGA between crisaborole and vehicle was statistically significantly different (p<0.001) in each study, with patients treated with crisaborole achieving success earlier than vehicle-treated patients. Percent of patients who achieved success in the ISGA: study AD-301, (crisaborole/vehicle), N=503/256, 32.8%/25.4% (p=0.038); study AD-302, (crisaborole/vehicle), N=513/250 31.4%/18% (p<0.001). In addition to the phase III pivotal studies, the company is conducting an open-label long-term safety study to evaluate the safety of intermittent use of crisaborole for up to 12 months.

July 21, 2014

Regeneron Pharmaceuticals and Sanofi reported results of a phase IIb trial of dupilumab in adult patients with moderate-to-severe atopic dermatitis (AD). This double-blind, placebo-controlled, 16-week, dose-ranging study enrolled 380 patients. Patients were randomized to receive one of five doses of dupilumab (300mg weekly, 300mg every other week, 300mg monthly, 200mg every other week, 100mg monthly) or placebo. The follow-up period of the study is ongoing and patients will be followed for 16 weeks after treatment. The improvements in Eczema Area and Severity Index (EASI) score ranged from a high of 74% for patients in the highest dose group, who received 300mg weekly, to a low of 45% in patients who received the lowest dose of 100mg monthly, compared to 18% for patients in the placebo group (p<0.0001 for all doses). 12% to 33% of dupilumab- treated patients achieved clearing or near-clearing of skin lesions, as measured by an investigator’s global assessment (IGA) score of 0 or 1, compared to 2% with placebo (p=0.02 to p<0.0001). Dupilumab-treated patients experienced a 16.5% to 47% mean reduction in itching, as measured by the pruritus numerical- rating scale (NRS) score, compared to an increase of 5% in the placebo group (p=0.0005 to p<0.0001).

March 11, 2013

Sanofi and Regeneron Pharmaceuticals issued pooled results from two phase Ib trials of dupilumab for atopic dermatitis. The trials enrolled a total of 67 subjects with moderate-to-severe atopic dermatitis not adequately controlled with topical medications. The subjects were randomized to three different doses of dupilumab (75mg, 150mg or 300mg) or placebo administered as weekly subcutaneous injections for four weeks. The efficacy data showed treatment with dupilumab at either 150mg or 300mg per week significantly improved the signs and symptoms of atopic dermatitis, with significant improvements in body surface area (BSA) score, Investigator Global Assessment (IGA) score and Eczema Area Severity Index (EASI) from baseline to week four, compared to placebo (p<0.05 vs. placebo for all measures and doses). The significant improvements in BSA, IGA and EASI scores were maintained at week eight in the 300mg dose group (p<0.05 vs. placebo). The most common adverse events were nasopharyngitis and headaches. A phase IIa trial is currently underway and a phase IIb trial is planned for later this year.

December 19, 2011

Anacor released results from two phase IIa trials of AN2728 and AN2898 for the treatment of atopic dermatitis. The six-week, double-blind, randomized trials enrolled 46 subjects with mild to moderate atopic dermatitis. Skin lesions were treated with 2% AN2728, 1% AN2898 or placebo ointments twice daily. The primary outcome measure was improvement of lesions for each treatment group, measured by the Atopic Dermatitis Severity Index (ADSI) score at 28 days post-treatment. The primary endpoint for both compounds was successfully achieved after 28 days of twice-daily treatment, with 64% of AN2728-treated lesions showing improvement on the ADSI score versus 24% for placebo (p≡0.05) and 71% of AN2898-treated lesions showing improvement on the ADSI score versus 14% for placebo (p≡0.01).

December 20, 2010

Creabilis issued positive results from a phase IIa trial of CT327 for the treatment of atopic dermatitis. This trial enrolled 15 subjects in Switzerland who received CT327 topically 0.1% cream twice daily for 15 days or placebo. A clinically significant improvement in symptoms was seen after eight days of treatment with CT327, as measured by change in mEASI (modified eczema area and severity index) score from baseline. Onset of efficacy was seen at three to five days of treatment. The greatest patient-reported benefit was in nighttime itch. CT327 was safe and well tolerated with no serious adverse events and no reported site irritation.

February 25, 2008

JADO Technologies issued positive results from a phase II trial of TF002 for the treatment of atopic dermatitis. This randomized, double-blind, active controlled trial enrolled seventeen subjects who received TF002 or hydrocortisone. The primary endpoint was the reduction of inflammation in atopic skin after three weeks, measured through a highly significant improvement in TIS (Three Item Severity) score. The endpoint was reached; both TF-002 and hydrocortisone improved three item severity scores by more than 1.5. At a four week follow-up, TF-002 showed continued benefit and did not induce skin atrophy when compared with hydrocortisone. TF002 also showed a trend towards reducing the total number of mast cells. Based on the results, JADO plans to move forward with the development of TF002.

July 9, 2007

Cytos issued mixed results from a phase IIa trial of CYT-003-QbG10 for the treatment of atopic dermatitis (AD). This randomized, double-blind and placebo-controlled trial enrolled 36 subjects withmild to moderate AD, as assessed by the Eczema Area Severity Index (EASI). Subjectswere randomized to two treatment groups and received 6 weekly subcutaneous injectionsof either 300 micrograms CYT003-QbG10 or placebo. Two weeks after the last dose,the disease status of the patients was again assessed by the EASI. Treatment wassafe and well tolerated. However, both the CYT003-QbG10 and placebo treatmentgroups showed a similar reduction of the EASI scores as measured over the studyperiod, indicating no treatment effect for CYT003-QbG10 in atopic dermatitis atthe dose level tested in this trial. Based on the results, Cytos is planning toconduct trials testing higher dose levels of CYT-003-QbG10 in order to determinea future path for this compound.

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