Psoriasis pipeline is full of biologics

CHICAGO – Most psoriasis therapies in the pipeline are biologics, including several interleukin (IL)-23 inhibitors and a promising dual inhibitor of IL-17A and IL-17F, so dermatologists are likely to gain a few more options for treating psoriasis patients who have not responded well to or tolerated existing therapies.

“The IL-23 blockers are ideal for patients who want a few injections,” Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and chair of the department of dermatology of the Mount Sinai Health System, said after the American Academy of Dermatology summer meeting. He discussed clinical trial results for risankizumab, mirikizumab, certolizumab pegol (which was recently approved for psoriasis), bimekizumab, as well as tildrakizumab, which has been approved by the Food and Drug Administration, but has not yet been released.

 

Tildrakizumab: The FDA approved tildrakizumab (Ilumya), a selective IL-23p19 inhibitor, for treatment of moderate to severe plaque psoriasis in March 2018 based on data from the reSURFACE 1 and reSURFACE 2 trials. After initial doses at weeks 0 and 4, patients received a 100-mg subcutaneous injection dose every 12 weeks. Results of reSURFACE 1 showed that 14% of trial participants achieved a Psoriasis Area and Severity Index (PASI) score of 100 with tildrakizumab at week 12, compared with 1% of those receiving a placebo. Similarly, 35% achieved a PASI 90 and 64% achieved a PASI 75 with the drug, compared with 3% and 6%, respectively, in the placebo group. Findings for reSURFACE 2 were similar; in a pooled analysis, a quarter of the 371 patients reached PASI 100 by week 28, 36% reached PASI 90-PASI 99, 24% reached PASI 75-PASI 89, and 10% reached PASI 50-PASI 74. Efficacy remained high 2 years after treatment, although body weight affected the efficacy. “The authors concluded that PASI and PGA [Physician Global Assessment] responses were numerically greater in patients with lower versus higher body weight,” Dr. Lebwohl said at the meeting.

Tildrakizumab also has an “overall clean safety profile,” he said. Among all patients treated in the trials, the rate of severe infections, malignancies and major adverse cardiac events did not significantly differ from placebo.*

Risankizumab: Also an IL-23 inhibitor, risankizumab, under FDA review for treatment of moderate to severe plaque psoriasis, outperformed both ustekinumab and adalimumab in pivotal phase 3 trials reported in October 2017. In the two ultlMMa trials, 75% of 598 total patients achieved a PASI 90 score after 16 weeks of treatment, compared with 2%-5% of placebo participants and 42%-48% of those on ustekinumab. In ultlMMa-1, just over a third of patients treated with achieved PASI 100, and just over half did in ultlMMa-2, compared with 12% and 24% of those on ustekinumab, respectively.

At 1 year, the proportion of those with PASI 90 rose to 82% in ultlMMa-1 and 81% in ultlMMa-2, with over half the participants achieving PASI 100 in both studies. The risankizumab trial findings were “among highest efficacy results reported to date, with impressive durability of response on and off drug,” Dr. Lebwohl said. “Preliminary safety is encouraging,” but “long-term data are required.”

Mirikizumab: Although not as far along in clinical trials, mirikizumab is another IL-23 inhibitor with “interesting and impressive preliminary results,” Dr. Lebwohl said. In a phase 2 trial of 205 participants whose baseline demographics indicated more severe psoriasis, 67% achieved PASI 90 at week 16 with a 300-mg dose (administered every 8 weeks). Doses of 100 mg and 30 mg resulted in 59% and 29% of participants achieving PASI 90 at week 16.

“The most common treatment emergent adverse events included upper respiratory tract infection [including viral], injection site pain, hypertension and diarrhea,” Dr. Lebwohl said. Patients are now being recruited for two phase 3 studies of mirikizumab (OASIS-1 and OASIS-2).

Certolizumab pegol: Certolizumab pegol is a tumor necrosis factor blocker approved in 2013 for treatment of psoriatic arthritis, and for moderate to severe plaque psoriasis in May 2018. In a pooled data analysis of three phase 3 trials (CIMPASI-1, CIMPASI-2, and CIMPACT), 52.3% of participants taking 400 mg subcutaneously every 2 weeks and 44.5% of those taking 200 mg every 2 weeks achieved PASI 90 at week 16, compared with 1.6% of those on placebo. In addition, a trial evaluating maternal transfer of certolizumab to the fetus via placenta found minimal drug concentration levels in the umbilical cord and infant’s plasma. “Certolizumab is ideal for women of childbearing potential,” Dr. Lebwohl said after the meeting.

Bimekizumab: This is a dual inhibitor of IL-17A and IL-17F being studied for treatment of mild psoriasis but “is very promising for psoriatic arthritis, as well as psoriasis,” Dr. Lebwohl said. In the phase 2b BE ABLE 1 trial, up to 79% of patients receiving bimekizumab achieved PASI 90 at week 12, and up to 46% of psoriatic arthritis patients had at least a 50% improvement in joint symptoms, compared with 7% of those on placebo.

Dr. Lebwohl is a consultant for Allergan, Boehringer-Ingelheim, Leo and Promius Pharma, and is an employee of Mount Sinai, which receives research funds from Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, Medimmune/AstraZeneca, Novartis, Pfizer, and ViDac Pharma.

*Correction, 8/6/18: An earlier version of this article misstated the adverse event data for tildrakizumab.

CHICAGO – Most psoriasis therapies in the pipeline are biologics, including several interleukin (IL)-23 inhibitors and a promising dual inhibitor of IL-17A and IL-17F, so dermatologists are likely to gain a few more options for treating psoriasis patients who have not responded well to or tolerated existing therapies.

“The IL-23 blockers are ideal for patients who want a few injections,” Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and chair of the department of dermatology of the Mount Sinai Health System, said after the American Academy of Dermatology summer meeting. He discussed clinical trial results for risankizumab, mirikizumab, certolizumab pegol (which was recently approved for psoriasis), bimekizumab, as well as tildrakizumab, which has been approved by the Food and Drug Administration, but has not yet been released.

 

Tildrakizumab: The FDA approved tildrakizumab (Ilumya), a selective IL-23p19 inhibitor, for treatment of moderate to severe plaque psoriasis in March 2018 based on data from the reSURFACE 1 and reSURFACE 2 trials. After initial doses at weeks 0 and 4, patients received a 100-mg subcutaneous injection dose every 12 weeks. Results of reSURFACE 1 showed that 14% of trial participants achieved a Psoriasis Area and Severity Index (PASI) score of 100 with tildrakizumab at week 12, compared with 1% of those receiving a placebo. Similarly, 35% achieved a PASI 90 and 64% achieved a PASI 75 with the drug, compared with 3% and 6%, respectively, in the placebo group. Findings for reSURFACE 2 were similar; in a pooled analysis, a quarter of the 371 patients reached PASI 100 by week 28, 36% reached PASI 90-PASI 99, 24% reached PASI 75-PASI 89, and 10% reached PASI 50-PASI 74. Efficacy remained high 2 years after treatment, although body weight affected the efficacy. “The authors concluded that PASI and PGA [Physician Global Assessment] responses were numerically greater in patients with lower versus higher body weight,” Dr. Lebwohl said at the meeting.

Tildrakizumab also has an “overall clean safety profile,” he said. Among all patients treated in the trials, the rate of severe infections, malignancies and major adverse cardiac events did not significantly differ from placebo.*

Risankizumab: Also an IL-23 inhibitor, risankizumab, under FDA review for treatment of moderate to severe plaque psoriasis, outperformed both ustekinumab and adalimumab in pivotal phase 3 trials reported in October 2017. In the two ultlMMa trials, 75% of 598 total patients achieved a PASI 90 score after 16 weeks of treatment, compared with 2%-5% of placebo participants and 42%-48% of those on ustekinumab. In ultlMMa-1, just over a third of patients treated with achieved PASI 100, and just over half did in ultlMMa-2, compared with 12% and 24% of those on ustekinumab, respectively.

At 1 year, the proportion of those with PASI 90 rose to 82% in ultlMMa-1 and 81% in ultlMMa-2, with over half the participants achieving PASI 100 in both studies. The risankizumab trial findings were “among highest efficacy results reported to date, with impressive durability of response on and off drug,” Dr. Lebwohl said. “Preliminary safety is encouraging,” but “long-term data are required.”

Mirikizumab: Although not as far along in clinical trials, mirikizumab is another IL-23 inhibitor with “interesting and impressive preliminary results,” Dr. Lebwohl said. In a phase 2 trial of 205 participants whose baseline demographics indicated more severe psoriasis, 67% achieved PASI 90 at week 16 with a 300-mg dose (administered every 8 weeks). Doses of 100 mg and 30 mg resulted in 59% and 29% of participants achieving PASI 90 at week 16.

“The most common treatment emergent adverse events included upper respiratory tract infection [including viral], injection site pain, hypertension and diarrhea,” Dr. Lebwohl said. Patients are now being recruited for two phase 3 studies of mirikizumab (OASIS-1 and OASIS-2).

Certolizumab pegol: Certolizumab pegol is a tumor necrosis factor blocker approved in 2013 for treatment of psoriatic arthritis, and for moderate to severe plaque psoriasis in May 2018. In a pooled data analysis of three phase 3 trials (CIMPASI-1, CIMPASI-2, and CIMPACT), 52.3% of participants taking 400 mg subcutaneously every 2 weeks and 44.5% of those taking 200 mg every 2 weeks achieved PASI 90 at week 16, compared with 1.6% of those on placebo. In addition, a trial evaluating maternal transfer of certolizumab to the fetus via placenta found minimal drug concentration levels in the umbilical cord and infant’s plasma. “Certolizumab is ideal for women of childbearing potential,” Dr. Lebwohl said after the meeting.

Bimekizumab: This is a dual inhibitor of IL-17A and IL-17F being studied for treatment of mild psoriasis but “is very promising for psoriatic arthritis, as well as psoriasis,” Dr. Lebwohl said. In the phase 2b BE ABLE 1 trial, up to 79% of patients receiving bimekizumab achieved PASI 90 at week 12, and up to 46% of psoriatic arthritis patients had at least a 50% improvement in joint symptoms, compared with 7% of those on placebo.

Dr. Lebwohl is a consultant for Allergan, Boehringer-Ingelheim, Leo and Promius Pharma, and is an employee of Mount Sinai, which receives research funds from Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, Medimmune/AstraZeneca, Novartis, Pfizer, and ViDac Pharma.

*Correction, 8/6/18: An earlier version of this article misstated the adverse event data for tildrakizumab.

CHICAGO – Most psoriasis therapies in the pipeline are biologics, including several interleukin (IL)-23 inhibitors and a promising dual inhibitor of IL-17A and IL-17F, so dermatologists are likely to gain a few more options for treating psoriasis patients who have not responded well to or tolerated existing therapies.

“The IL-23 blockers are ideal for patients who want a few injections,” Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and chair of the department of dermatology of the Mount Sinai Health System, said after the American Academy of Dermatology summer meeting. He discussed clinical trial results for risankizumab, mirikizumab, certolizumab pegol (which was recently approved for psoriasis), bimekizumab, as well as tildrakizumab, which has been approved by the Food and Drug Administration, but has not yet been released.

 

Tildrakizumab: The FDA approved tildrakizumab (Ilumya), a selective IL-23p19 inhibitor, for treatment of moderate to severe plaque psoriasis in March 2018 based on data from the reSURFACE 1 and reSURFACE 2 trials. After initial doses at weeks 0 and 4, patients received a 100-mg subcutaneous injection dose every 12 weeks. Results of reSURFACE 1 showed that 14% of trial participants achieved a Psoriasis Area and Severity Index (PASI) score of 100 with tildrakizumab at week 12, compared with 1% of those receiving a placebo. Similarly, 35% achieved a PASI 90 and 64% achieved a PASI 75 with the drug, compared with 3% and 6%, respectively, in the placebo group. Findings for reSURFACE 2 were similar; in a pooled analysis, a quarter of the 371 patients reached PASI 100 by week 28, 36% reached PASI 90-PASI 99, 24% reached PASI 75-PASI 89, and 10% reached PASI 50-PASI 74. Efficacy remained high 2 years after treatment, although body weight affected the efficacy. “The authors concluded that PASI and PGA [Physician Global Assessment] responses were numerically greater in patients with lower versus higher body weight,” Dr. Lebwohl said at the meeting.

Tildrakizumab also has an “overall clean safety profile,” he said. Among all patients treated in the trials, the rate of severe infections, malignancies and major adverse cardiac events did not significantly differ from placebo.*

Risankizumab: Also an IL-23 inhibitor, risankizumab, under FDA review for treatment of moderate to severe plaque psoriasis, outperformed both ustekinumab and adalimumab in pivotal phase 3 trials reported in October 2017. In the two ultlMMa trials, 75% of 598 total patients achieved a PASI 90 score after 16 weeks of treatment, compared with 2%-5% of placebo participants and 42%-48% of those on ustekinumab. In ultlMMa-1, just over a third of patients treated with achieved PASI 100, and just over half did in ultlMMa-2, compared with 12% and 24% of those on ustekinumab, respectively.

At 1 year, the proportion of those with PASI 90 rose to 82% in ultlMMa-1 and 81% in ultlMMa-2, with over half the participants achieving PASI 100 in both studies. The risankizumab trial findings were “among highest efficacy results reported to date, with impressive durability of response on and off drug,” Dr. Lebwohl said. “Preliminary safety is encouraging,” but “long-term data are required.”

Mirikizumab: Although not as far along in clinical trials, mirikizumab is another IL-23 inhibitor with “interesting and impressive preliminary results,” Dr. Lebwohl said. In a phase 2 trial of 205 participants whose baseline demographics indicated more severe psoriasis, 67% achieved PASI 90 at week 16 with a 300-mg dose (administered every 8 weeks). Doses of 100 mg and 30 mg resulted in 59% and 29% of participants achieving PASI 90 at week 16.

“The most common treatment emergent adverse events included upper respiratory tract infection [including viral], injection site pain, hypertension and diarrhea,” Dr. Lebwohl said. Patients are now being recruited for two phase 3 studies of mirikizumab (OASIS-1 and OASIS-2).

Certolizumab pegol: Certolizumab pegol is a tumor necrosis factor blocker approved in 2013 for treatment of psoriatic arthritis, and for moderate to severe plaque psoriasis in May 2018. In a pooled data analysis of three phase 3 trials (CIMPASI-1, CIMPASI-2, and CIMPACT), 52.3% of participants taking 400 mg subcutaneously every 2 weeks and 44.5% of those taking 200 mg every 2 weeks achieved PASI 90 at week 16, compared with 1.6% of those on placebo. In addition, a trial evaluating maternal transfer of certolizumab to the fetus via placenta found minimal drug concentration levels in the umbilical cord and infant’s plasma. “Certolizumab is ideal for women of childbearing potential,” Dr. Lebwohl said after the meeting.

Bimekizumab: This is a dual inhibitor of IL-17A and IL-17F being studied for treatment of mild psoriasis but “is very promising for psoriatic arthritis, as well as psoriasis,” Dr. Lebwohl said. In the phase 2b BE ABLE 1 trial, up to 79% of patients receiving bimekizumab achieved PASI 90 at week 12, and up to 46% of psoriatic arthritis patients had at least a 50% improvement in joint symptoms, compared with 7% of those on placebo.

Dr. Lebwohl is a consultant for Allergan, Boehringer-Ingelheim, Leo and Promius Pharma, and is an employee of Mount Sinai, which receives research funds from Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, Medimmune/AstraZeneca, Novartis, Pfizer, and ViDac Pharma.

*Correction, 8/6/18: An earlier version of this article misstated the adverse event data for tildrakizumab.