EADV: Another promising topical for atopic dermatitis

COPENHAGEN – A novel topical nonsteroidal inhibitor of phosphodiesterase-4 showed a favorable efficacy to side effect ratio in a phase II study of adolescents and adults with mild to moderate atopic dermatitis, Dr. Jon M. Hanifin reported at the annual congress of the European Academy of Dermatology and Venereology.

“For topical agents, I think a 30% improvement with few side effects is a desirable balance,” observed Dr. Hanifin of Oregon Health and Sciences University, Portland.

The investigational agent, known for now as OPA-15406, is formulated as a twice-daily ointment. It is highly selective for the phosphodiesterase-4 (PDE-4) B subtype.

Dr. Hanifin noted that these are “exciting times” in the development of new topical therapies for atopic dermatitis (AD). In addition to the successful phase II study of OPA-15406 he presented, a highlight of the EADV congress was the strongly positive pivotal phase III data presented for crisaborole, another nonsteroidal topical PDE-4 inhibitor, albeit with a different mechanism of action.

For Dr. Hanifin these developments are particularly satisfying personally because 33 years ago as a young investigator – before the term ‘translational science’ had come into vogue – he and his research team made the seminal observation that increased phosphodiesterase activity is “a basic biochemical characteristic relevant to skin immunocellular regulation in atopic disease” (J Allergy Clin Immunol. 1982 Dec;70[6]:452-7).

The 8-week, multicenter, randomized, double-blind phase II OPA-15406 dose-ranging study included 121 patients, 70% with moderate AD, the rest with mild disease. About 20% were adolescents, the rest adults. Their mean baseline Eczema Area Severity Index (EASI) score was 9.5, with a self-reported pruritus score of 61 on a 0-100 scale. Participants were randomized to twice-daily application of OPA-15406 at 0.3% or 1% or the vehicle ointment as a control.

A significant treatment effect was seen within the first week. At 1 week, the mean EASI score was reduced by 31% from baseline in the 1% OPA-15406 group, 15% with the 0.3% formulation, and 6% with vehicle. The active treatment remained significantly more effective than vehicle throughout the 8-week period.

Another measure of efficacy – an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 along with at least a 2-point improvement on the 0-5 scale at week 4 – was met by 21% of patients on 1% OPA-15406, 15% on the 0.3% formulation, and 2.7% on vehicle. By the less stringent standard of an IGA of 0 or 1 plus at least a 1-point reduction at week 4, the success rates were 30%, 24%, and 10%.

Dr. Hanifin said the 1% formulation is the one likely to advance to phase III studies, given its superior efficacy. This was particularly evident with regard to itch. At the first evaluation, after just 1 week of treatment, pruritus scores showed a mean 30% reduction with 1% OPA-15406 versus no significant change in controls. He added that his clinical impression is that many patients experience a significant improvement in itching within the first 24 hours on the 1% formulation, an observation that deserves formal study.

Scores on the Dermatology Life Quality Index and Children’s Dermatology Life Quality Index were significantly better in the active therapy arms than with vehicle as early as week 1.

The adverse events findings were “not very exciting,” according to the dermatologist. No treatment-related serious adverse events occurred. The two most common adverse events leading to treatment discontinuation – worsening AD and pruritus – occurred more often in the vehicle-treated controls.

Session cochair Dr. Jacek Szepietowski called the pruritus results particularly impressive.

“It’s very difficult to do successful clinical trials of topicals for atopic dermatitis because the vehicle alone, especially if it’s an ointment, can have favorable effects which increase over time both on EASI and pruritus,” commented Dr. Szepietowski, professor and head of the department of dermatology, venereology, and allergology at the Medical University of Wroclaw (Poland).

The study was sponsored by Otsuka Pharmaceuticals. Dr. Hanifin reported serving as a consultant to and paid investigator for the company.

[email protected]

COPENHAGEN – A novel topical nonsteroidal inhibitor of phosphodiesterase-4 showed a favorable efficacy to side effect ratio in a phase II study of adolescents and adults with mild to moderate atopic dermatitis, Dr. Jon M. Hanifin reported at the annual congress of the European Academy of Dermatology and Venereology.

“For topical agents, I think a 30% improvement with few side effects is a desirable balance,” observed Dr. Hanifin of Oregon Health and Sciences University, Portland.

The investigational agent, known for now as OPA-15406, is formulated as a twice-daily ointment. It is highly selective for the phosphodiesterase-4 (PDE-4) B subtype.

Dr. Hanifin noted that these are “exciting times” in the development of new topical therapies for atopic dermatitis (AD). In addition to the successful phase II study of OPA-15406 he presented, a highlight of the EADV congress was the strongly positive pivotal phase III data presented for crisaborole, another nonsteroidal topical PDE-4 inhibitor, albeit with a different mechanism of action.

For Dr. Hanifin these developments are particularly satisfying personally because 33 years ago as a young investigator – before the term ‘translational science’ had come into vogue – he and his research team made the seminal observation that increased phosphodiesterase activity is “a basic biochemical characteristic relevant to skin immunocellular regulation in atopic disease” (J Allergy Clin Immunol. 1982 Dec;70[6]:452-7).

The 8-week, multicenter, randomized, double-blind phase II OPA-15406 dose-ranging study included 121 patients, 70% with moderate AD, the rest with mild disease. About 20% were adolescents, the rest adults. Their mean baseline Eczema Area Severity Index (EASI) score was 9.5, with a self-reported pruritus score of 61 on a 0-100 scale. Participants were randomized to twice-daily application of OPA-15406 at 0.3% or 1% or the vehicle ointment as a control.

A significant treatment effect was seen within the first week. At 1 week, the mean EASI score was reduced by 31% from baseline in the 1% OPA-15406 group, 15% with the 0.3% formulation, and 6% with vehicle. The active treatment remained significantly more effective than vehicle throughout the 8-week period.

Another measure of efficacy – an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 along with at least a 2-point improvement on the 0-5 scale at week 4 – was met by 21% of patients on 1% OPA-15406, 15% on the 0.3% formulation, and 2.7% on vehicle. By the less stringent standard of an IGA of 0 or 1 plus at least a 1-point reduction at week 4, the success rates were 30%, 24%, and 10%.

Dr. Hanifin said the 1% formulation is the one likely to advance to phase III studies, given its superior efficacy. This was particularly evident with regard to itch. At the first evaluation, after just 1 week of treatment, pruritus scores showed a mean 30% reduction with 1% OPA-15406 versus no significant change in controls. He added that his clinical impression is that many patients experience a significant improvement in itching within the first 24 hours on the 1% formulation, an observation that deserves formal study.

Scores on the Dermatology Life Quality Index and Children’s Dermatology Life Quality Index were significantly better in the active therapy arms than with vehicle as early as week 1.

The adverse events findings were “not very exciting,” according to the dermatologist. No treatment-related serious adverse events occurred. The two most common adverse events leading to treatment discontinuation – worsening AD and pruritus – occurred more often in the vehicle-treated controls.

Session cochair Dr. Jacek Szepietowski called the pruritus results particularly impressive.

“It’s very difficult to do successful clinical trials of topicals for atopic dermatitis because the vehicle alone, especially if it’s an ointment, can have favorable effects which increase over time both on EASI and pruritus,” commented Dr. Szepietowski, professor and head of the department of dermatology, venereology, and allergology at the Medical University of Wroclaw (Poland).

The study was sponsored by Otsuka Pharmaceuticals. Dr. Hanifin reported serving as a consultant to and paid investigator for the company.

[email protected]

COPENHAGEN – A novel topical nonsteroidal inhibitor of phosphodiesterase-4 showed a favorable efficacy to side effect ratio in a phase II study of adolescents and adults with mild to moderate atopic dermatitis, Dr. Jon M. Hanifin reported at the annual congress of the European Academy of Dermatology and Venereology.

“For topical agents, I think a 30% improvement with few side effects is a desirable balance,” observed Dr. Hanifin of Oregon Health and Sciences University, Portland.

The investigational agent, known for now as OPA-15406, is formulated as a twice-daily ointment. It is highly selective for the phosphodiesterase-4 (PDE-4) B subtype.

Dr. Hanifin noted that these are “exciting times” in the development of new topical therapies for atopic dermatitis (AD). In addition to the successful phase II study of OPA-15406 he presented, a highlight of the EADV congress was the strongly positive pivotal phase III data presented for crisaborole, another nonsteroidal topical PDE-4 inhibitor, albeit with a different mechanism of action.

For Dr. Hanifin these developments are particularly satisfying personally because 33 years ago as a young investigator – before the term ‘translational science’ had come into vogue – he and his research team made the seminal observation that increased phosphodiesterase activity is “a basic biochemical characteristic relevant to skin immunocellular regulation in atopic disease” (J Allergy Clin Immunol. 1982 Dec;70[6]:452-7).

The 8-week, multicenter, randomized, double-blind phase II OPA-15406 dose-ranging study included 121 patients, 70% with moderate AD, the rest with mild disease. About 20% were adolescents, the rest adults. Their mean baseline Eczema Area Severity Index (EASI) score was 9.5, with a self-reported pruritus score of 61 on a 0-100 scale. Participants were randomized to twice-daily application of OPA-15406 at 0.3% or 1% or the vehicle ointment as a control.

A significant treatment effect was seen within the first week. At 1 week, the mean EASI score was reduced by 31% from baseline in the 1% OPA-15406 group, 15% with the 0.3% formulation, and 6% with vehicle. The active treatment remained significantly more effective than vehicle throughout the 8-week period.

Another measure of efficacy – an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 along with at least a 2-point improvement on the 0-5 scale at week 4 – was met by 21% of patients on 1% OPA-15406, 15% on the 0.3% formulation, and 2.7% on vehicle. By the less stringent standard of an IGA of 0 or 1 plus at least a 1-point reduction at week 4, the success rates were 30%, 24%, and 10%.

Dr. Hanifin said the 1% formulation is the one likely to advance to phase III studies, given its superior efficacy. This was particularly evident with regard to itch. At the first evaluation, after just 1 week of treatment, pruritus scores showed a mean 30% reduction with 1% OPA-15406 versus no significant change in controls. He added that his clinical impression is that many patients experience a significant improvement in itching within the first 24 hours on the 1% formulation, an observation that deserves formal study.

Scores on the Dermatology Life Quality Index and Children’s Dermatology Life Quality Index were significantly better in the active therapy arms than with vehicle as early as week 1.

The adverse events findings were “not very exciting,” according to the dermatologist. No treatment-related serious adverse events occurred. The two most common adverse events leading to treatment discontinuation – worsening AD and pruritus – occurred more often in the vehicle-treated controls.

Session cochair Dr. Jacek Szepietowski called the pruritus results particularly impressive.

“It’s very difficult to do successful clinical trials of topicals for atopic dermatitis because the vehicle alone, especially if it’s an ointment, can have favorable effects which increase over time both on EASI and pruritus,” commented Dr. Szepietowski, professor and head of the department of dermatology, venereology, and allergology at the Medical University of Wroclaw (Poland).

The study was sponsored by Otsuka Pharmaceuticals. Dr. Hanifin reported serving as a consultant to and paid investigator for the company.

[email protected]