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Society for Pediatric Dermatology (SPD): Pre-American Academy of Dermatology Meeting
Psoriatic pruritus improves with TrkA-blocking drug
An investigational topical drug that targets a nerve sensitization pathway showed good efficacy against chronic itch in patients with pruritic psoriasis.
CT327 works by inhibiting the kinase pathway of TrkA, a receptor that controls uptake of nerve growth factor, Dr. Gil Yosipovitch said at the annual meeting of the American Academy of Dermatology.
In a placebo-controlled trial of 160 patients with pruritic psoriasis, CT327 reduced itch by a mean of 60%, said Dr. Yosipovitch, chair of dermatology at the Temple University, Philadelphia.
"Sixty percent is not 90%," he said. "But when we consider that most of the antipruritic drugs have about a 15% efficacy in comparison to a vehicle, this is an effect we should consider. It’s well tolerated, and there were no application site reactions. I see potential in this drug."
CT327, developed by Creabilis, is a selective kinase inhibitor that targets TrkA, the receptor for nerve growth factor (NGF). NGF, which is overexpressed in atopic dermatitis and psoriatic skin, sensitizes neural networks that transmit the itch sensation to the brain, Dr. Yosipovitch said.
The phase IIb study comprised 160 adults with mild to moderate psoriasis, with at least a 10% body surface area involvement. Their mean score on the modified Psoriasis Area and Severity Index (mPASI) was about 9. Most (97%) had pruritus; 69% reported this as at least moderate, with a score of 40 on a 100-point visual analog scale (VAS). A third of the group reported severe pruritus, with a VAS of more than 70. They were randomized to four groups: an emollient placebo or CT327 in concentrations of 0.05%, 0.1%, or 0.5%.
The primary endpoint was reduction on a validated 100-point pruritus visual analog scale. The secondary endpoint was change on the mPASI.
By the end of 8 weeks, most patients (108) had experienced a significant reduction on the pruritus VAS. Reductions were about 35 points for the 0.1% group and 38 points for the 0.05% and 0.5% groups. These changes represented about a 60% decrease overall, Dr. Yosipovitch said.
Changes began early and continued along a steep trajectory, reaching a significant difference from baseline by week 2. However, he pointed out, by that point, the placebo group was similarly improved. This was probably because of the benefit of the daily emollient vehicle, he noted.
The curves began to separate shortly thereafter. By week 4, all of the treatment groups had experienced about a 30-point reduction on the VAS, while the placebo group had actually increased its score slightly. The active groups continued to improve over the next 4 weeks, while the placebo group plateaued at about a 20-point decrease from baseline.
The study concluded with 4 weeks of non–treatment follow-up. During that time, the placebo group stayed at about a 20-point decline and the active groups rebounded to about that level, "suggesting that there really is something going on here biologically," Dr. Yosipovitch said.
Patients using CT327 also experienced significant – although not overwhelming – benefit on the mPASI score. About 45% responded at the 50% level, compared with 23% of those using the emollient placebo. The active groups had similar improvements, with reductions on the mPASI of between 3 and 4 points. Those in the placebo group experienced about a 1-point improvement.
Dr. Yosipovitch said he was "not too impressed" with the mPASI changes. However, he noted, "Breaking the itch-scratch cycle at its source may have broader effects on other symptoms of psoriasis."
Based on the study results, Creabilis has decided to move forward into phase III testing with the 0.05% concentration. "Preparations are already underway," Dr. Yosipovitch said in an interview. "We also have a second phase IIb study ongoing that is investigating CT327 in patients with atopic dermatitis, which will be used to help finalize our phase III programs. This study should be completed in the middle of this year."
The NGF/TrkA pathway is implicated in other disorders as well, Dr. Yosipovitch said. CT327 might be investigated in some of these.
"These include disorders [in which] pruritus is important, such as pruritus with cutaneous T cell lymphoma, where NGF/TrkA has been shown to play a role. The pathway has also been shown to play an important role in chronic neuropathic and inflammatory pain. Molecules targeting NGF have already shown clinical efficacy."
Creabilis is investigating a related molecule, CT340, an inhibitor of both TrkA and MAP2K kinase, for treating those chronic pain conditions.
Creabilis funded the study. Dr. Yosipovitch is on the company’s scientific advisory board.
On Twitter @alz_gal
An investigational topical drug that targets a nerve sensitization pathway showed good efficacy against chronic itch in patients with pruritic psoriasis.
CT327 works by inhibiting the kinase pathway of TrkA, a receptor that controls uptake of nerve growth factor, Dr. Gil Yosipovitch said at the annual meeting of the American Academy of Dermatology.
In a placebo-controlled trial of 160 patients with pruritic psoriasis, CT327 reduced itch by a mean of 60%, said Dr. Yosipovitch, chair of dermatology at the Temple University, Philadelphia.
"Sixty percent is not 90%," he said. "But when we consider that most of the antipruritic drugs have about a 15% efficacy in comparison to a vehicle, this is an effect we should consider. It’s well tolerated, and there were no application site reactions. I see potential in this drug."
CT327, developed by Creabilis, is a selective kinase inhibitor that targets TrkA, the receptor for nerve growth factor (NGF). NGF, which is overexpressed in atopic dermatitis and psoriatic skin, sensitizes neural networks that transmit the itch sensation to the brain, Dr. Yosipovitch said.
The phase IIb study comprised 160 adults with mild to moderate psoriasis, with at least a 10% body surface area involvement. Their mean score on the modified Psoriasis Area and Severity Index (mPASI) was about 9. Most (97%) had pruritus; 69% reported this as at least moderate, with a score of 40 on a 100-point visual analog scale (VAS). A third of the group reported severe pruritus, with a VAS of more than 70. They were randomized to four groups: an emollient placebo or CT327 in concentrations of 0.05%, 0.1%, or 0.5%.
The primary endpoint was reduction on a validated 100-point pruritus visual analog scale. The secondary endpoint was change on the mPASI.
By the end of 8 weeks, most patients (108) had experienced a significant reduction on the pruritus VAS. Reductions were about 35 points for the 0.1% group and 38 points for the 0.05% and 0.5% groups. These changes represented about a 60% decrease overall, Dr. Yosipovitch said.
Changes began early and continued along a steep trajectory, reaching a significant difference from baseline by week 2. However, he pointed out, by that point, the placebo group was similarly improved. This was probably because of the benefit of the daily emollient vehicle, he noted.
The curves began to separate shortly thereafter. By week 4, all of the treatment groups had experienced about a 30-point reduction on the VAS, while the placebo group had actually increased its score slightly. The active groups continued to improve over the next 4 weeks, while the placebo group plateaued at about a 20-point decrease from baseline.
The study concluded with 4 weeks of non–treatment follow-up. During that time, the placebo group stayed at about a 20-point decline and the active groups rebounded to about that level, "suggesting that there really is something going on here biologically," Dr. Yosipovitch said.
Patients using CT327 also experienced significant – although not overwhelming – benefit on the mPASI score. About 45% responded at the 50% level, compared with 23% of those using the emollient placebo. The active groups had similar improvements, with reductions on the mPASI of between 3 and 4 points. Those in the placebo group experienced about a 1-point improvement.
Dr. Yosipovitch said he was "not too impressed" with the mPASI changes. However, he noted, "Breaking the itch-scratch cycle at its source may have broader effects on other symptoms of psoriasis."
Based on the study results, Creabilis has decided to move forward into phase III testing with the 0.05% concentration. "Preparations are already underway," Dr. Yosipovitch said in an interview. "We also have a second phase IIb study ongoing that is investigating CT327 in patients with atopic dermatitis, which will be used to help finalize our phase III programs. This study should be completed in the middle of this year."
The NGF/TrkA pathway is implicated in other disorders as well, Dr. Yosipovitch said. CT327 might be investigated in some of these.
"These include disorders [in which] pruritus is important, such as pruritus with cutaneous T cell lymphoma, where NGF/TrkA has been shown to play a role. The pathway has also been shown to play an important role in chronic neuropathic and inflammatory pain. Molecules targeting NGF have already shown clinical efficacy."
Creabilis is investigating a related molecule, CT340, an inhibitor of both TrkA and MAP2K kinase, for treating those chronic pain conditions.
Creabilis funded the study. Dr. Yosipovitch is on the company’s scientific advisory board.
On Twitter @alz_gal
An investigational topical drug that targets a nerve sensitization pathway showed good efficacy against chronic itch in patients with pruritic psoriasis.
CT327 works by inhibiting the kinase pathway of TrkA, a receptor that controls uptake of nerve growth factor, Dr. Gil Yosipovitch said at the annual meeting of the American Academy of Dermatology.
In a placebo-controlled trial of 160 patients with pruritic psoriasis, CT327 reduced itch by a mean of 60%, said Dr. Yosipovitch, chair of dermatology at the Temple University, Philadelphia.
"Sixty percent is not 90%," he said. "But when we consider that most of the antipruritic drugs have about a 15% efficacy in comparison to a vehicle, this is an effect we should consider. It’s well tolerated, and there were no application site reactions. I see potential in this drug."
CT327, developed by Creabilis, is a selective kinase inhibitor that targets TrkA, the receptor for nerve growth factor (NGF). NGF, which is overexpressed in atopic dermatitis and psoriatic skin, sensitizes neural networks that transmit the itch sensation to the brain, Dr. Yosipovitch said.
The phase IIb study comprised 160 adults with mild to moderate psoriasis, with at least a 10% body surface area involvement. Their mean score on the modified Psoriasis Area and Severity Index (mPASI) was about 9. Most (97%) had pruritus; 69% reported this as at least moderate, with a score of 40 on a 100-point visual analog scale (VAS). A third of the group reported severe pruritus, with a VAS of more than 70. They were randomized to four groups: an emollient placebo or CT327 in concentrations of 0.05%, 0.1%, or 0.5%.
The primary endpoint was reduction on a validated 100-point pruritus visual analog scale. The secondary endpoint was change on the mPASI.
By the end of 8 weeks, most patients (108) had experienced a significant reduction on the pruritus VAS. Reductions were about 35 points for the 0.1% group and 38 points for the 0.05% and 0.5% groups. These changes represented about a 60% decrease overall, Dr. Yosipovitch said.
Changes began early and continued along a steep trajectory, reaching a significant difference from baseline by week 2. However, he pointed out, by that point, the placebo group was similarly improved. This was probably because of the benefit of the daily emollient vehicle, he noted.
The curves began to separate shortly thereafter. By week 4, all of the treatment groups had experienced about a 30-point reduction on the VAS, while the placebo group had actually increased its score slightly. The active groups continued to improve over the next 4 weeks, while the placebo group plateaued at about a 20-point decrease from baseline.
The study concluded with 4 weeks of non–treatment follow-up. During that time, the placebo group stayed at about a 20-point decline and the active groups rebounded to about that level, "suggesting that there really is something going on here biologically," Dr. Yosipovitch said.
Patients using CT327 also experienced significant – although not overwhelming – benefit on the mPASI score. About 45% responded at the 50% level, compared with 23% of those using the emollient placebo. The active groups had similar improvements, with reductions on the mPASI of between 3 and 4 points. Those in the placebo group experienced about a 1-point improvement.
Dr. Yosipovitch said he was "not too impressed" with the mPASI changes. However, he noted, "Breaking the itch-scratch cycle at its source may have broader effects on other symptoms of psoriasis."
Based on the study results, Creabilis has decided to move forward into phase III testing with the 0.05% concentration. "Preparations are already underway," Dr. Yosipovitch said in an interview. "We also have a second phase IIb study ongoing that is investigating CT327 in patients with atopic dermatitis, which will be used to help finalize our phase III programs. This study should be completed in the middle of this year."
The NGF/TrkA pathway is implicated in other disorders as well, Dr. Yosipovitch said. CT327 might be investigated in some of these.
"These include disorders [in which] pruritus is important, such as pruritus with cutaneous T cell lymphoma, where NGF/TrkA has been shown to play a role. The pathway has also been shown to play an important role in chronic neuropathic and inflammatory pain. Molecules targeting NGF have already shown clinical efficacy."
Creabilis is investigating a related molecule, CT340, an inhibitor of both TrkA and MAP2K kinase, for treating those chronic pain conditions.
Creabilis funded the study. Dr. Yosipovitch is on the company’s scientific advisory board.
On Twitter @alz_gal
AT THE AAD ANNUAL MEETING
Major finding: The investigational drug CT327 reduced pruritus scores by 60% in a group of pruritic psoriatic patients.
Data source: The randomized, placebo-controlled trial of 160 patients.
Disclosures: Creabilis funded the study. Dr. Gil Yosipovitch is on the company’s scientific advisory board.
VIDEO: Vitiligo gene hunt could open door to eventual drug treatment
DENVER – Vitiligo has been known for thousands of years, but only in the past six decades have researchers begun to better understand it and uncover genes associated with the disorder.
Dr. Richard A. Spritz, one of the leaders in vitiligo research, says that scientists are very close to understanding the condition’s pathogenesis. He is embarking on another analysis of data from a large genetic study, which could double the number of known vitiligo genes, putting the disorder on par with other autoimmune diseases such as type 1 diabetes and rheumatoid arthritis.
At the Society of Pediatric Dermatology’s annual meeting, held immediately before the annual meeting of the American Academy of Dermatology, Dr. Spritz spoke about what is known so far about vitiligo and what the future holds. Dr. Spritz is professor and director of the Human Medical Genetics and Genomics Program at the University of Colorado, Aurora.
On Twitter @naseemsmiller
DENVER – Vitiligo has been known for thousands of years, but only in the past six decades have researchers begun to better understand it and uncover genes associated with the disorder.
Dr. Richard A. Spritz, one of the leaders in vitiligo research, says that scientists are very close to understanding the condition’s pathogenesis. He is embarking on another analysis of data from a large genetic study, which could double the number of known vitiligo genes, putting the disorder on par with other autoimmune diseases such as type 1 diabetes and rheumatoid arthritis.
At the Society of Pediatric Dermatology’s annual meeting, held immediately before the annual meeting of the American Academy of Dermatology, Dr. Spritz spoke about what is known so far about vitiligo and what the future holds. Dr. Spritz is professor and director of the Human Medical Genetics and Genomics Program at the University of Colorado, Aurora.
On Twitter @naseemsmiller
DENVER – Vitiligo has been known for thousands of years, but only in the past six decades have researchers begun to better understand it and uncover genes associated with the disorder.
Dr. Richard A. Spritz, one of the leaders in vitiligo research, says that scientists are very close to understanding the condition’s pathogenesis. He is embarking on another analysis of data from a large genetic study, which could double the number of known vitiligo genes, putting the disorder on par with other autoimmune diseases such as type 1 diabetes and rheumatoid arthritis.
At the Society of Pediatric Dermatology’s annual meeting, held immediately before the annual meeting of the American Academy of Dermatology, Dr. Spritz spoke about what is known so far about vitiligo and what the future holds. Dr. Spritz is professor and director of the Human Medical Genetics and Genomics Program at the University of Colorado, Aurora.
On Twitter @naseemsmiller
AT A MEETING OF THE SOCIETY OF PEDIATRIC DERMATOLOGY
AAD 2014 sessions offer something for everyone
The American Academy’s 2014 annual meeting in Denver will feature new CME sessions and updates on the latest dermatology research.
This year’s program features expert commentary on key issues in medical dermatology, including "Melanoma Multidisciplinary Care 2014: What You Need to Know" on Sunday, March 23, from 1 p.m. to 3 p.m. in Room 705/707 and "Dermatologic Manifestations of New Oncology Drugs," also on Sunday, March 23, from 1 p.m. to 3 p.m. in the Mile High Ballroom 3B. Looking for the latest in aesthetic dermatology? Check out the "Advanced Botulinum Toxin" live demonstration session on Saturday, March 22, from 2 p.m. to 5 p.m. in the Bellco Theater.
There will be expert sessions on pregnancy dermatoses, cutaneous T-cell lymphoma, pediatric dermatology, skin of color, and the latest on treatments for hair and nail conditions. The full scientific session list is available online.
A series of practice management lectures includes topics such as "How to Have an Unforgettably Positive Office Visit" on Saturday, March 22, from 10:00 a.m. to 12:00 p.m. in Room 709/7111 and "Hot Buttons: Recognizing What Sets You Off and Managing Your Triggers" on Sunday, March 23, from 1:00 p.m. to 3:00 p.m. in Room 702.
There is also a mobile device app that meeting attendees can download that contains session schedules, exhibitor and attendee lists, and more.
Can’t attend the meeting? Visit www.eDermatologyNews.com for live conference coverage.
On Twitter @Sknews
The American Academy’s 2014 annual meeting in Denver will feature new CME sessions and updates on the latest dermatology research.
This year’s program features expert commentary on key issues in medical dermatology, including "Melanoma Multidisciplinary Care 2014: What You Need to Know" on Sunday, March 23, from 1 p.m. to 3 p.m. in Room 705/707 and "Dermatologic Manifestations of New Oncology Drugs," also on Sunday, March 23, from 1 p.m. to 3 p.m. in the Mile High Ballroom 3B. Looking for the latest in aesthetic dermatology? Check out the "Advanced Botulinum Toxin" live demonstration session on Saturday, March 22, from 2 p.m. to 5 p.m. in the Bellco Theater.
There will be expert sessions on pregnancy dermatoses, cutaneous T-cell lymphoma, pediatric dermatology, skin of color, and the latest on treatments for hair and nail conditions. The full scientific session list is available online.
A series of practice management lectures includes topics such as "How to Have an Unforgettably Positive Office Visit" on Saturday, March 22, from 10:00 a.m. to 12:00 p.m. in Room 709/7111 and "Hot Buttons: Recognizing What Sets You Off and Managing Your Triggers" on Sunday, March 23, from 1:00 p.m. to 3:00 p.m. in Room 702.
There is also a mobile device app that meeting attendees can download that contains session schedules, exhibitor and attendee lists, and more.
Can’t attend the meeting? Visit www.eDermatologyNews.com for live conference coverage.
On Twitter @Sknews
The American Academy’s 2014 annual meeting in Denver will feature new CME sessions and updates on the latest dermatology research.
This year’s program features expert commentary on key issues in medical dermatology, including "Melanoma Multidisciplinary Care 2014: What You Need to Know" on Sunday, March 23, from 1 p.m. to 3 p.m. in Room 705/707 and "Dermatologic Manifestations of New Oncology Drugs," also on Sunday, March 23, from 1 p.m. to 3 p.m. in the Mile High Ballroom 3B. Looking for the latest in aesthetic dermatology? Check out the "Advanced Botulinum Toxin" live demonstration session on Saturday, March 22, from 2 p.m. to 5 p.m. in the Bellco Theater.
There will be expert sessions on pregnancy dermatoses, cutaneous T-cell lymphoma, pediatric dermatology, skin of color, and the latest on treatments for hair and nail conditions. The full scientific session list is available online.
A series of practice management lectures includes topics such as "How to Have an Unforgettably Positive Office Visit" on Saturday, March 22, from 10:00 a.m. to 12:00 p.m. in Room 709/7111 and "Hot Buttons: Recognizing What Sets You Off and Managing Your Triggers" on Sunday, March 23, from 1:00 p.m. to 3:00 p.m. in Room 702.
There is also a mobile device app that meeting attendees can download that contains session schedules, exhibitor and attendee lists, and more.
Can’t attend the meeting? Visit www.eDermatologyNews.com for live conference coverage.
On Twitter @Sknews