Brodalumab met primary endpoints, deaths called ‘unrelated’

The investigational interleukin-17 inhibitor brodalumab met both primary endpoints in a phase III, double-blind, placebo-controlled trial of 661 patients with moderate to severe plaque psoriasis, investigators reported in the British Journal of Dermatology.

By week 12, 83% of patients on 210 mg brodalumab achieved Psoriasis Area and Severity Index (PASI) 75, as did 60% of patients on 140 mg and 3% of placebo patients, said Dr. Kim Papp of Probity Medical Research in Waterloo, Ont., and associates. The coprimary endpoint, a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear skin), was achieved by 76%, 54%, and 1% of patients, respectively. “Skin clearance continues to improve beyond 12 weeks, and is sustained through 1 year of therapy,” and the safety profile “was considered to be acceptable,” the researchers said.

Courtesy Centers for Disease Control and Prevention

The AMAGINE-1 trial included a 12-week induction period followed by a withdrawal-retreatment period lasting up to 52 weeks. At the end of induction, brodalumab patients who achieved sPGA 0/1 were rerandomized to placebo or to induction dose. Four weeks later, those with sPGA scores of at least 3 received another induction dose. After 12 weeks of retreatment, patients scoring sPGA 2/3 were rescued with brodalumab 210 mg every 2 weeks (Br J Dermatol. 2016 Feb 23. doi: 10.1111/bjd.14493).

The psoriasis community has closely watched brodalumab, which handily beat ustekinumab in the AMAGINE-2 psoriasis trial before Amgen abruptly pulled out of development in the wake of two suicides by trial participants. AstraZeneca and Valeant Pharmaceuticals then partnered on the agent, and the Food and Drug Administration accepted a Biologics License Application in January 2016.

Dr. Papp and associates published details of the suicides, noting that one involved a 59-year-old man who died 2 months after his last 210-mg dose. He had no history of psychiatric disorders and normal baseline Hospital Anxiety and Depression Scale scores, which worsened on placebo but normalized by week 52. “The investigator reported that there was no reasonable possibility that the event of suicide was related to investigational product,” the researchers said. The second suicide involved a 56-year-old man who also received 210 mg brodalumab. He had a history of severe depression, but his Hospital Anxiety and Depression Scale (HADS) scores were normal when last assessed, his psoriasis was well controlled, and his death was considered unrelated to treatment. Indeed, moderate or severe baseline HADS scores were more likely to improve when patients received brodalumab instead of placebo, the researchers said. The other two deaths on study involved patients with substantial cardiovascular and hepatic comorbidities and also were considered unrelated to treatment.

Amgen and AstraZeneca/MedImmune funded the study, and Amgen analyzed the data. Dr. Papp reported having served as a consultant, investigator, and speaker for Amgen and numerous other pharmaceutical companies. Ten coinvestigators also reported relationships with Amgen and other pharmaceutical companies, and six coinvestigators reported current or former employment with Amgen.

The investigational interleukin-17 inhibitor brodalumab met both primary endpoints in a phase III, double-blind, placebo-controlled trial of 661 patients with moderate to severe plaque psoriasis, investigators reported in the British Journal of Dermatology.

By week 12, 83% of patients on 210 mg brodalumab achieved Psoriasis Area and Severity Index (PASI) 75, as did 60% of patients on 140 mg and 3% of placebo patients, said Dr. Kim Papp of Probity Medical Research in Waterloo, Ont., and associates. The coprimary endpoint, a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear skin), was achieved by 76%, 54%, and 1% of patients, respectively. “Skin clearance continues to improve beyond 12 weeks, and is sustained through 1 year of therapy,” and the safety profile “was considered to be acceptable,” the researchers said.

Courtesy Centers for Disease Control and Prevention

The AMAGINE-1 trial included a 12-week induction period followed by a withdrawal-retreatment period lasting up to 52 weeks. At the end of induction, brodalumab patients who achieved sPGA 0/1 were rerandomized to placebo or to induction dose. Four weeks later, those with sPGA scores of at least 3 received another induction dose. After 12 weeks of retreatment, patients scoring sPGA 2/3 were rescued with brodalumab 210 mg every 2 weeks (Br J Dermatol. 2016 Feb 23. doi: 10.1111/bjd.14493).

The psoriasis community has closely watched brodalumab, which handily beat ustekinumab in the AMAGINE-2 psoriasis trial before Amgen abruptly pulled out of development in the wake of two suicides by trial participants. AstraZeneca and Valeant Pharmaceuticals then partnered on the agent, and the Food and Drug Administration accepted a Biologics License Application in January 2016.

Dr. Papp and associates published details of the suicides, noting that one involved a 59-year-old man who died 2 months after his last 210-mg dose. He had no history of psychiatric disorders and normal baseline Hospital Anxiety and Depression Scale scores, which worsened on placebo but normalized by week 52. “The investigator reported that there was no reasonable possibility that the event of suicide was related to investigational product,” the researchers said. The second suicide involved a 56-year-old man who also received 210 mg brodalumab. He had a history of severe depression, but his Hospital Anxiety and Depression Scale (HADS) scores were normal when last assessed, his psoriasis was well controlled, and his death was considered unrelated to treatment. Indeed, moderate or severe baseline HADS scores were more likely to improve when patients received brodalumab instead of placebo, the researchers said. The other two deaths on study involved patients with substantial cardiovascular and hepatic comorbidities and also were considered unrelated to treatment.

Amgen and AstraZeneca/MedImmune funded the study, and Amgen analyzed the data. Dr. Papp reported having served as a consultant, investigator, and speaker for Amgen and numerous other pharmaceutical companies. Ten coinvestigators also reported relationships with Amgen and other pharmaceutical companies, and six coinvestigators reported current or former employment with Amgen.

The investigational interleukin-17 inhibitor brodalumab met both primary endpoints in a phase III, double-blind, placebo-controlled trial of 661 patients with moderate to severe plaque psoriasis, investigators reported in the British Journal of Dermatology.

By week 12, 83% of patients on 210 mg brodalumab achieved Psoriasis Area and Severity Index (PASI) 75, as did 60% of patients on 140 mg and 3% of placebo patients, said Dr. Kim Papp of Probity Medical Research in Waterloo, Ont., and associates. The coprimary endpoint, a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear skin), was achieved by 76%, 54%, and 1% of patients, respectively. “Skin clearance continues to improve beyond 12 weeks, and is sustained through 1 year of therapy,” and the safety profile “was considered to be acceptable,” the researchers said.

Courtesy Centers for Disease Control and Prevention

The AMAGINE-1 trial included a 12-week induction period followed by a withdrawal-retreatment period lasting up to 52 weeks. At the end of induction, brodalumab patients who achieved sPGA 0/1 were rerandomized to placebo or to induction dose. Four weeks later, those with sPGA scores of at least 3 received another induction dose. After 12 weeks of retreatment, patients scoring sPGA 2/3 were rescued with brodalumab 210 mg every 2 weeks (Br J Dermatol. 2016 Feb 23. doi: 10.1111/bjd.14493).

The psoriasis community has closely watched brodalumab, which handily beat ustekinumab in the AMAGINE-2 psoriasis trial before Amgen abruptly pulled out of development in the wake of two suicides by trial participants. AstraZeneca and Valeant Pharmaceuticals then partnered on the agent, and the Food and Drug Administration accepted a Biologics License Application in January 2016.

Dr. Papp and associates published details of the suicides, noting that one involved a 59-year-old man who died 2 months after his last 210-mg dose. He had no history of psychiatric disorders and normal baseline Hospital Anxiety and Depression Scale scores, which worsened on placebo but normalized by week 52. “The investigator reported that there was no reasonable possibility that the event of suicide was related to investigational product,” the researchers said. The second suicide involved a 56-year-old man who also received 210 mg brodalumab. He had a history of severe depression, but his Hospital Anxiety and Depression Scale (HADS) scores were normal when last assessed, his psoriasis was well controlled, and his death was considered unrelated to treatment. Indeed, moderate or severe baseline HADS scores were more likely to improve when patients received brodalumab instead of placebo, the researchers said. The other two deaths on study involved patients with substantial cardiovascular and hepatic comorbidities and also were considered unrelated to treatment.

Amgen and AstraZeneca/MedImmune funded the study, and Amgen analyzed the data. Dr. Papp reported having served as a consultant, investigator, and speaker for Amgen and numerous other pharmaceutical companies. Ten coinvestigators also reported relationships with Amgen and other pharmaceutical companies, and six coinvestigators reported current or former employment with Amgen.