Novel Biologic for Plaque Psoriasis Continues to Demonstrate Efficacy and Safety in Phase III Trial

Ixekizumab, a drug being evaluated for the treatment of moderate-to-severe chronic plaque psoriasis, continues to demonstrate efficacy and safety in Phase III trials.

In the current study, patients were grouped into three different study arms. All patients were randomized to receive either placebo or ixekizumab every two or four weeks for 12 weeks for the control portion of the study. In UNCOVER 1, patients responding to treatment continued to take either placebo or ixekizumab for up to 60 weeks. In the latter two groups, UNCOVER 2 and UNCOVER 3, patients could also receive etanercept (Enbrel), another biologic agent, twice weekly.

Patients receiving ixekizumab had significantly greater clearance of psoriatic plaques. More than three quarters of patients (78%-90%) receiving the investigational drug experienced at least a 75% reduction in Psoriasis Area and Severity Index scores (PASI 75) at 12 weeks. Additionally, 31% to 41% of these patients achieved PASI 100, or clear skin, at Week 12. As a point of comparison, it is noted that 5% to 7% of patients treated with etanercept in UNCOVER 2 and 3 achieved PASI 100.

Adverse events for patients receiving ixekizumab were comparable in the 12-week, randomized control portion across the three treatment arms. The most frequently reported events (those accounting for more than five percent of events across all three studies) were nasopharyngitis and injection site reactions. Most injection site reactions were mild and most patients who experienced this type of adverse event continued treatment with ixekizumab. The overall rate and severity of adverse events to ixekizumab in the two active comparator trials were comparable to those for etanercept.

This particular biologic is among a new class of agents for psoriasis that target the immune system molecule IL-17. Specifically, ixekizumab is a monoclonal antibody with high affinity and specificity that binds to, and neutralizes, the pro-inflammatory cytokine IL-17A. IL-17 is a cytokine involved in inflammation that is impaired in patients with psoriasis. According to the National Psoriasis Foundation, ixekizumab is one of several new drugs for chronic plaque psoriasis targeting IL-17 that are showing “unprecedented success.”

Etanercept, the other biologic agent used in the UNCOVER Phase III trial, is a tumor necrosis factor inhibitor.

Eli Lilly also recently announced some of its plans for ixekizumab in the coming year. The company noted that, in 2015, it will submit data from the UNCOVER studies for disclosure at scientific meetings and within clinical journals. According to a press release from the company, it will submit ixekizumab to regulatory authorities in the first half of 2015.

"Ixekizumab was discovered and engineered to achieve high affinity and specificity to the IL-17A cytokine by Lilly Research Laboratories scientists and is the most advanced asset in Lilly's pipeline of biotechnology-based medicines for the treatment of autoimmune diseases," said Tom Bumol, PhD, senior vice president of biotech discovery research, Lilly Research Laboratories, and president, Applied Molecular Evolution. "These data appear to confirm our hypothesis — that IL-17A is a major driver of excess keratinocyte (skin cell) proliferation and activation in psoriasis. We're encouraged that this discovery by Lilly scientists could provide a new treatment option for patients with moderate-to-severe plaque psoriasis."

Ixekizumab is also being investigated for the treatment of psoriatic arthritis.

In the coming weeks, look for coverage from HCPLive of two more drugs in development for psoriasis: ponesimod and itolizumab.