Results from a phase 2b dose-ranging study of Dupilumab, an investigational therapy, in adult patients with moderate-to-severe atopic dermatitis, a serious, chronic form of eczema were presented. All doses of Dupilumab met the primary endpoint of a greater improvement in Eczema Area and Severity Index ( EASI ) scores from baseline compared to placebo.
In addition, four earlier clinical studies of Dupilumab in moderate-to-severe atopic dermatitis were published in the New England Journal of Medicine ( NEJM ).
Dupilumab is an investigational monoclonal antibody that blocks signaling of IL-4 and IL-13, two cytokines that play a key role in the pathogenesis of moderate-to-severe atopic dermatitis.
In the phase 2b trial, all five subcutaneous doses of Dupilumab showed a dose-dependent improvement in the primary endpoint, the mean percent change in EASI score from baseline to week 16.
The improvements in EASI score ranged from a high of 74% for patients in the highest dose group, who received 300 mg weekly, to a low of 45% in patients who received the lowest dose of 100 mg monthly, compared to 18% for patients in the placebo group ( p less than 0.0001 for all doses ).
The most common adverse event in the phase 2b study was nasopharyngitis, which was balanced across Dupilumab treatment groups ( 18.5 to 23% ) compared to placebo ( 21% ).
Injection site reactions were more frequent in the Dupilumab group ( 5 to 9.5% ) compared to placebo ( 3% ), as was headache ( 12 to 15% ) compared to placebo ( 8% ).
Dupilumab-treated patients showed highly statistically significant and dose-dependent improvements in additional key efficacy measures compared to placebo after 16 weeks of treatment:
• 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 less than 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 less than 0.0001 ).
This phase 2b double-blind, placebo-controlled, 16-week, dose-ranging study randomized 380 patients with moderate-to-severe atopic dermatitis, who could not be adequately controlled with topical medication or for whom topical treatment was not advisable.
Patients were randomized to receive one of five doses of Dupilumab ( 300 mg weekly, 300 mg every other week, 300 mg monthly, 200 mg every other week, 100 mg monthly ) or placebo.
Patients in the study had approximately 50% of their skin affected by atopic dermatitis at baseline. Within the past year, approximately 35% of patients received an oral corticosteroid and approximately 20% received a systemic immunosuppressant for atopic dermatitis.
Approximately 60% of patients had another allergic condition, including approximately 40% of patients who had a history of asthma.
The New England Journal of Medicine publication has included data from four placebo-controlled studies, which all evaluated weekly subcutaneous doses of Dupilumab.
This included a phase 2a 12-week monotherapy study, a phase 2a, four-week study of Dupilumab in combination with topical glucocorticoids and two phase 1 four-week monotherapy studies.
In these studies, the most common adverse effects were nasopharyngitis and headache, which occurred with a higher frequency in the Dupilumab group.
Treatment with Dupilumab, either as a monotherapy or in combination, was associated with improvement in skin lesions and substantial improvements in pruritus.
Moderate-to-severe atopic dermatitis, a serious, chronic form of eczema, is a systemic inflammatory disease characterized by an allergic response driven by a subset of immune cells called type 2 helper T cells, or Th2 cells. IL-4 and IL-13 are key cytokines that are required for the initiation and maintenance of this Th2 immune response.
Moderate-to-severe forms of atopic dermatitis can be characterized by pronounced cutaneous dryness, and skin lesions marked by redness, infiltration / papulation, crusting / oozing, and lichenification, with periods of lesion exacerbation accompanied by intense itching, scratching, and skin damage that can lead to secondary infections. ( Xagena )
Source: Sanofi, 2014