Novel agent for papulopustular rosacea found safe, effective in phase III trials

DENVER – Ivermectin 1% cream applied once daily was effective and safe in treating patients with moderate to severe papulopustular rosacea, based on data from a pair of phase III studies.

Ivermectin 1% cream, a novel agent being developed by Galderma Laboratories, is of interest to rosacea researchers because it possesses unique anti-inflammatory and anti-parasitic properties, Dr. Linda Stein Gold said at the annual meeting of the American Academy of Dermatology.

Dr. Stein Gold of the department of dermatology at Henry Ford Medical Center, Detroit, explained that Demodex folliculorum, which is typically found on the human face, may trigger an immune response in rosacea patients. Ivermectin 1% is anti-parasitic against Demodex, providing an "innovative treatment" option in this patient population, she said. The investigational agent has not yet been approved by the Food and Drug Administration.

Dr. Stein Gold and her associates set out to assess the efficacy and safety of 1% ivermectin cream vs. a control vehicle cream in patients with moderate to severe papulopustular rosacea. The design included two identical, double-blind, parallel group, 12-week studies.

In both studies, a total of 910 patients were randomized 2:1 to receive 1% ivermectin cream or a control cream once daily. There were two co-primary endpoints: the percentage of patients who achieved a "clear" or "almost clear" score on the Investigator’s Global Assessment (IGA) scale at week 12, and the change in inflammatory lesion counts from baseline to week 12. The secondary efficacy endpoint assessment was the percentage change in inflammatory lesion count from baseline to week 12. The researchers also assessed safety endpoints by examining adverse events.

The mean age of patients was 50 years, 96% were white, and 67% were women. Patients had about 30 lesions each; 76-82% were classified as having moderate rosacea based on IGA score, and the rest had severe disease. More than 90% of patients in each arm completed the study through week 12.

At week 12 in both studies, a significantly higher percentage of patients in the treatment group achieved treatment success compared with those in the control group (38-40% vs. 12-19%, respectively; P less than .001). That difference was seen as early as week four.

Both studies also demonstrated that treatment with ivermectin 1% was significantly superior to the control vehicle in reducing lesion counts, with significance seen as early as week two and continuing for the duration of the study. Patients in the treatment groups in both studies showed an average reduction of more than 20 lesions, while controls in the two studies had reductions of 12 and 13.4 lesions, respectively.

Fewer treatment-related adverse events were reported in the ivermectin group, compared with the control group (3.4% vs. 7.2%, respectively). The most common treatment-related adverse event in the first study was sensation of skin burning (1.8% in the ivermectin group vs. 2.6% in controls) while the most common adverse event in the second study were pruritus and dry skin (0.7% and 0.9%, respectively). "This drug was exceptionally well tolerated, very safe as well as efficacious," Dr. Stein Gold said.

In an interview, she acknowledged certain limitations of the study, including the fact that "we did not look at maintenance of efficacy when a patient stops the drug. However, that is being looked at in other studies."

The study was funded by Galderma R&D. Dr. Stein Gold disclosed that she is a consultant for Galderma.

dbrunk@frontlinemedcom.com

DENVER – Ivermectin 1% cream applied once daily was effective and safe in treating patients with moderate to severe papulopustular rosacea, based on data from a pair of phase III studies.

Ivermectin 1% cream, a novel agent being developed by Galderma Laboratories, is of interest to rosacea researchers because it possesses unique anti-inflammatory and anti-parasitic properties, Dr. Linda Stein Gold said at the annual meeting of the American Academy of Dermatology.

Dr. Stein Gold of the department of dermatology at Henry Ford Medical Center, Detroit, explained that Demodex folliculorum, which is typically found on the human face, may trigger an immune response in rosacea patients. Ivermectin 1% is anti-parasitic against Demodex, providing an "innovative treatment" option in this patient population, she said. The investigational agent has not yet been approved by the Food and Drug Administration.

Dr. Stein Gold and her associates set out to assess the efficacy and safety of 1% ivermectin cream vs. a control vehicle cream in patients with moderate to severe papulopustular rosacea. The design included two identical, double-blind, parallel group, 12-week studies.

In both studies, a total of 910 patients were randomized 2:1 to receive 1% ivermectin cream or a control cream once daily. There were two co-primary endpoints: the percentage of patients who achieved a "clear" or "almost clear" score on the Investigator’s Global Assessment (IGA) scale at week 12, and the change in inflammatory lesion counts from baseline to week 12. The secondary efficacy endpoint assessment was the percentage change in inflammatory lesion count from baseline to week 12. The researchers also assessed safety endpoints by examining adverse events.

The mean age of patients was 50 years, 96% were white, and 67% were women. Patients had about 30 lesions each; 76-82% were classified as having moderate rosacea based on IGA score, and the rest had severe disease. More than 90% of patients in each arm completed the study through week 12.

At week 12 in both studies, a significantly higher percentage of patients in the treatment group achieved treatment success compared with those in the control group (38-40% vs. 12-19%, respectively; P less than .001). That difference was seen as early as week four.

Both studies also demonstrated that treatment with ivermectin 1% was significantly superior to the control vehicle in reducing lesion counts, with significance seen as early as week two and continuing for the duration of the study. Patients in the treatment groups in both studies showed an average reduction of more than 20 lesions, while controls in the two studies had reductions of 12 and 13.4 lesions, respectively.

Fewer treatment-related adverse events were reported in the ivermectin group, compared with the control group (3.4% vs. 7.2%, respectively). The most common treatment-related adverse event in the first study was sensation of skin burning (1.8% in the ivermectin group vs. 2.6% in controls) while the most common adverse event in the second study were pruritus and dry skin (0.7% and 0.9%, respectively). "This drug was exceptionally well tolerated, very safe as well as efficacious," Dr. Stein Gold said.

In an interview, she acknowledged certain limitations of the study, including the fact that "we did not look at maintenance of efficacy when a patient stops the drug. However, that is being looked at in other studies."

The study was funded by Galderma R&D. Dr. Stein Gold disclosed that she is a consultant for Galderma.

dbrunk@frontlinemedcom.com

DENVER – Ivermectin 1% cream applied once daily was effective and safe in treating patients with moderate to severe papulopustular rosacea, based on data from a pair of phase III studies.

Ivermectin 1% cream, a novel agent being developed by Galderma Laboratories, is of interest to rosacea researchers because it possesses unique anti-inflammatory and anti-parasitic properties, Dr. Linda Stein Gold said at the annual meeting of the American Academy of Dermatology.

Dr. Stein Gold of the department of dermatology at Henry Ford Medical Center, Detroit, explained that Demodex folliculorum, which is typically found on the human face, may trigger an immune response in rosacea patients. Ivermectin 1% is anti-parasitic against Demodex, providing an "innovative treatment" option in this patient population, she said. The investigational agent has not yet been approved by the Food and Drug Administration.

Dr. Stein Gold and her associates set out to assess the efficacy and safety of 1% ivermectin cream vs. a control vehicle cream in patients with moderate to severe papulopustular rosacea. The design included two identical, double-blind, parallel group, 12-week studies.

In both studies, a total of 910 patients were randomized 2:1 to receive 1% ivermectin cream or a control cream once daily. There were two co-primary endpoints: the percentage of patients who achieved a "clear" or "almost clear" score on the Investigator’s Global Assessment (IGA) scale at week 12, and the change in inflammatory lesion counts from baseline to week 12. The secondary efficacy endpoint assessment was the percentage change in inflammatory lesion count from baseline to week 12. The researchers also assessed safety endpoints by examining adverse events.

The mean age of patients was 50 years, 96% were white, and 67% were women. Patients had about 30 lesions each; 76-82% were classified as having moderate rosacea based on IGA score, and the rest had severe disease. More than 90% of patients in each arm completed the study through week 12.

At week 12 in both studies, a significantly higher percentage of patients in the treatment group achieved treatment success compared with those in the control group (38-40% vs. 12-19%, respectively; P less than .001). That difference was seen as early as week four.

Both studies also demonstrated that treatment with ivermectin 1% was significantly superior to the control vehicle in reducing lesion counts, with significance seen as early as week two and continuing for the duration of the study. Patients in the treatment groups in both studies showed an average reduction of more than 20 lesions, while controls in the two studies had reductions of 12 and 13.4 lesions, respectively.

Fewer treatment-related adverse events were reported in the ivermectin group, compared with the control group (3.4% vs. 7.2%, respectively). The most common treatment-related adverse event in the first study was sensation of skin burning (1.8% in the ivermectin group vs. 2.6% in controls) while the most common adverse event in the second study were pruritus and dry skin (0.7% and 0.9%, respectively). "This drug was exceptionally well tolerated, very safe as well as efficacious," Dr. Stein Gold said.

In an interview, she acknowledged certain limitations of the study, including the fact that "we did not look at maintenance of efficacy when a patient stops the drug. However, that is being looked at in other studies."

The study was funded by Galderma R&D. Dr. Stein Gold disclosed that she is a consultant for Galderma.

dbrunk@frontlinemedcom.com