Investigational Biologic Rocks Psoriasis World

COPENHAGEN – An investigational biologic agent that selectively inhibits the p19 subunit of interleukin-23 was the talk of the 2015 EADV congress based upon its striking outperformance of ustekinumab in a head-to-head phase II study in psoriasis patients.

Not only did the investigational agent, known for now as BI 655066, achieve substantially higher rates of PASI 90 – clear or almost clear skin – and PASI 100, but it did so much faster and maintained those stellar results far longer off treatment than with ustekinumab (Stelara), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.

“These data make an irrefutable case for IL-23 as instrumental in the expression of psoriasis,” declared Dr. Papp, president of Probity Medical Research in Waterloo, Ont.

“What these data show is that selective blockade of IL-23 p19 clearly provides a remarkable response, whether we measure it as PASI 75, PASI 90, or PASI 100, compared with ustekinumab, which provides a very robust response itself. And when we look at the safety profile – admittedly in a small number of patients and for a short period of time – we see there are no real differences in safety signals. Obviously, we’re very encouraged to move forward with long-term phase III investigations,” Dr. Papp added.

The multicenter, double-blind phase II study included 166 patients with moderate to severe plaque psoriasis who were randomized to one of four treatment arms: BI 655066 at 90 or 180 mg given subcutaneously at weeks 0, 4, and 16; weight-based ustekinumab at 45 or 90 mg given on the same schedule; or a single 18-mg dose of BI 655066. Dr. Papp presented the results at 36 weeks, fully 20 weeks after the final dose was given.

Significantly more patients taking the investigational agent achieved PASI targets than did those taking ustekinumab, a highly effective medication. Here are the eye-popping 36-week results:

• PASI 90: 81% with BI 655066 at 180 mg, 69% with the lower dose, 30% with ustekinumab, and 7% with a single 18-mg dose of BI 655066.

• PASI 100: 54% and 43% with high- and low-dose BI 655066, respectively, 15% with ustekinumab, and 0% with single-dose BI 655066.

• PASI 75: 93% and 88% with high- and low-dose BI 655066; 55% with ustekinumab; and 19% after single-dose BI 655066.

One of the most intriguing study findings, according to Dr. Papp, is that the slope of the PASI 100 response curve in BI 655066–treated patients was still rising at week 20, a month after the final dose.

“It suggests that if you were to continue treating these patients, you might anticipate an even higher response,” the dermatologist said.

Another notable finding was the accelerated speed of response to the investigational agent: 57 days after the first dose of BI 655066, 50% of patients had a PASI 90 response.

“That means from the time you initiate therapy, you can expect half of your patients to get to PASI 90 in less than 2 months time,” Dr. Papp observed.

In contrast, it took 117 days – basically twice as long – for half of the ustekinumab group to achieve PASI 90.

Turning to the durability of response, Dr. Papp noted that it took 169 days for half of patients in the ustekinumab group to lose their PASI 90 response after treatment stopped, compared with 225 days in the BI 655066 90-mg group. That endpoint was never reached in the BI 655066 180-mg group before the study’s end.

Audience reaction to the study results was “wow.”

“Obviously, the data are terrific. Your mother couldn’t have invented better data,” declared Dr. Alice B. Gottlieb, professor of dermatology and dermatologist in chief at Tufts Medical Center, Boston.

She posed a question: Why are the BI 655066 response rates so much higher and longer lasting than with other biologics, including ustekinumab, which inhibits both IL-23 and IL-12?

“I think one key factor in the durability of the response is the pathway,” Dr. Papp replied. “Exactly why blockade of IL-23 p19 leads to this durable clinical response is unclear, but we can posit that we’re depopulating the Th-17 cells. IL-23 is necessary for Th-17 cell survival. So if you block the water, you ain’t going to grow the grass. I’m speculating here, but I think we’re removing that clone of cells, and it’s only once we start to allow them to repopulate that we then see recurrence of the disease.”

BI 655066 is being developed by Boehringer Ingelheim. Dr. Papp serves as an investigator for and consultant to Boehringer Ingelheim and numerous other pharmaceutical companies.

COPENHAGEN – An investigational biologic agent that selectively inhibits the p19 subunit of interleukin-23 was the talk of the 2015 EADV congress based upon its striking outperformance of ustekinumab in a head-to-head phase II study in psoriasis patients.

Not only did the investigational agent, known for now as BI 655066, achieve substantially higher rates of PASI 90 – clear or almost clear skin – and PASI 100, but it did so much faster and maintained those stellar results far longer off treatment than with ustekinumab (Stelara), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.

“These data make an irrefutable case for IL-23 as instrumental in the expression of psoriasis,” declared Dr. Papp, president of Probity Medical Research in Waterloo, Ont.

“What these data show is that selective blockade of IL-23 p19 clearly provides a remarkable response, whether we measure it as PASI 75, PASI 90, or PASI 100, compared with ustekinumab, which provides a very robust response itself. And when we look at the safety profile – admittedly in a small number of patients and for a short period of time – we see there are no real differences in safety signals. Obviously, we’re very encouraged to move forward with long-term phase III investigations,” Dr. Papp added.

The multicenter, double-blind phase II study included 166 patients with moderate to severe plaque psoriasis who were randomized to one of four treatment arms: BI 655066 at 90 or 180 mg given subcutaneously at weeks 0, 4, and 16; weight-based ustekinumab at 45 or 90 mg given on the same schedule; or a single 18-mg dose of BI 655066. Dr. Papp presented the results at 36 weeks, fully 20 weeks after the final dose was given.

Significantly more patients taking the investigational agent achieved PASI targets than did those taking ustekinumab, a highly effective medication. Here are the eye-popping 36-week results:

• PASI 90: 81% with BI 655066 at 180 mg, 69% with the lower dose, 30% with ustekinumab, and 7% with a single 18-mg dose of BI 655066.

• PASI 100: 54% and 43% with high- and low-dose BI 655066, respectively, 15% with ustekinumab, and 0% with single-dose BI 655066.

• PASI 75: 93% and 88% with high- and low-dose BI 655066; 55% with ustekinumab; and 19% after single-dose BI 655066.

One of the most intriguing study findings, according to Dr. Papp, is that the slope of the PASI 100 response curve in BI 655066–treated patients was still rising at week 20, a month after the final dose.

“It suggests that if you were to continue treating these patients, you might anticipate an even higher response,” the dermatologist said.

Another notable finding was the accelerated speed of response to the investigational agent: 57 days after the first dose of BI 655066, 50% of patients had a PASI 90 response.

“That means from the time you initiate therapy, you can expect half of your patients to get to PASI 90 in less than 2 months time,” Dr. Papp observed.

In contrast, it took 117 days – basically twice as long – for half of the ustekinumab group to achieve PASI 90.

Turning to the durability of response, Dr. Papp noted that it took 169 days for half of patients in the ustekinumab group to lose their PASI 90 response after treatment stopped, compared with 225 days in the BI 655066 90-mg group. That endpoint was never reached in the BI 655066 180-mg group before the study’s end.

Audience reaction to the study results was “wow.”

“Obviously, the data are terrific. Your mother couldn’t have invented better data,” declared Dr. Alice B. Gottlieb, professor of dermatology and dermatologist in chief at Tufts Medical Center, Boston.

She posed a question: Why are the BI 655066 response rates so much higher and longer lasting than with other biologics, including ustekinumab, which inhibits both IL-23 and IL-12?

“I think one key factor in the durability of the response is the pathway,” Dr. Papp replied. “Exactly why blockade of IL-23 p19 leads to this durable clinical response is unclear, but we can posit that we’re depopulating the Th-17 cells. IL-23 is necessary for Th-17 cell survival. So if you block the water, you ain’t going to grow the grass. I’m speculating here, but I think we’re removing that clone of cells, and it’s only once we start to allow them to repopulate that we then see recurrence of the disease.”

BI 655066 is being developed by Boehringer Ingelheim. Dr. Papp serves as an investigator for and consultant to Boehringer Ingelheim and numerous other pharmaceutical companies.

COPENHAGEN – An investigational biologic agent that selectively inhibits the p19 subunit of interleukin-23 was the talk of the 2015 EADV congress based upon its striking outperformance of ustekinumab in a head-to-head phase II study in psoriasis patients.

Not only did the investigational agent, known for now as BI 655066, achieve substantially higher rates of PASI 90 – clear or almost clear skin – and PASI 100, but it did so much faster and maintained those stellar results far longer off treatment than with ustekinumab (Stelara), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.

“These data make an irrefutable case for IL-23 as instrumental in the expression of psoriasis,” declared Dr. Papp, president of Probity Medical Research in Waterloo, Ont.

“What these data show is that selective blockade of IL-23 p19 clearly provides a remarkable response, whether we measure it as PASI 75, PASI 90, or PASI 100, compared with ustekinumab, which provides a very robust response itself. And when we look at the safety profile – admittedly in a small number of patients and for a short period of time – we see there are no real differences in safety signals. Obviously, we’re very encouraged to move forward with long-term phase III investigations,” Dr. Papp added.

The multicenter, double-blind phase II study included 166 patients with moderate to severe plaque psoriasis who were randomized to one of four treatment arms: BI 655066 at 90 or 180 mg given subcutaneously at weeks 0, 4, and 16; weight-based ustekinumab at 45 or 90 mg given on the same schedule; or a single 18-mg dose of BI 655066. Dr. Papp presented the results at 36 weeks, fully 20 weeks after the final dose was given.

Significantly more patients taking the investigational agent achieved PASI targets than did those taking ustekinumab, a highly effective medication. Here are the eye-popping 36-week results:

• PASI 90: 81% with BI 655066 at 180 mg, 69% with the lower dose, 30% with ustekinumab, and 7% with a single 18-mg dose of BI 655066.

• PASI 100: 54% and 43% with high- and low-dose BI 655066, respectively, 15% with ustekinumab, and 0% with single-dose BI 655066.

• PASI 75: 93% and 88% with high- and low-dose BI 655066; 55% with ustekinumab; and 19% after single-dose BI 655066.

One of the most intriguing study findings, according to Dr. Papp, is that the slope of the PASI 100 response curve in BI 655066–treated patients was still rising at week 20, a month after the final dose.

“It suggests that if you were to continue treating these patients, you might anticipate an even higher response,” the dermatologist said.

Another notable finding was the accelerated speed of response to the investigational agent: 57 days after the first dose of BI 655066, 50% of patients had a PASI 90 response.

“That means from the time you initiate therapy, you can expect half of your patients to get to PASI 90 in less than 2 months time,” Dr. Papp observed.

In contrast, it took 117 days – basically twice as long – for half of the ustekinumab group to achieve PASI 90.

Turning to the durability of response, Dr. Papp noted that it took 169 days for half of patients in the ustekinumab group to lose their PASI 90 response after treatment stopped, compared with 225 days in the BI 655066 90-mg group. That endpoint was never reached in the BI 655066 180-mg group before the study’s end.

Audience reaction to the study results was “wow.”

“Obviously, the data are terrific. Your mother couldn’t have invented better data,” declared Dr. Alice B. Gottlieb, professor of dermatology and dermatologist in chief at Tufts Medical Center, Boston.

She posed a question: Why are the BI 655066 response rates so much higher and longer lasting than with other biologics, including ustekinumab, which inhibits both IL-23 and IL-12?

“I think one key factor in the durability of the response is the pathway,” Dr. Papp replied. “Exactly why blockade of IL-23 p19 leads to this durable clinical response is unclear, but we can posit that we’re depopulating the Th-17 cells. IL-23 is necessary for Th-17 cell survival. So if you block the water, you ain’t going to grow the grass. I’m speculating here, but I think we’re removing that clone of cells, and it’s only once we start to allow them to repopulate that we then see recurrence of the disease.”

BI 655066 is being developed by Boehringer Ingelheim. Dr. Papp serves as an investigator for and consultant to Boehringer Ingelheim and numerous other pharmaceutical companies.