Psoriasis Drug Ixekizumab Superior to Etanercept in Phase III Studies
Regulatory submission expected in early 2015
The investigational medication ixekizumab (Eli Lilly) has been shown to be statistically superior to etanercept and placebo on all skin-clearance measures in patients with moderate-to-severe plaque psoriasis.
Patients were assigned to receive either ixekizumab (80 mg every 2 or 4 weeks) or placebo for 12 weeks, following a 160-mg starting dose, in three phase III trials (UNCOVER-1, -2, and -3). In the two active-comparator studies (UNCOVER-2 and -3), patients could be assigned to receive etanercept 50 mg twice weekly for 12 weeks. In the UNCOVER-1 trial, responders to treatment were assigned to continue treatment with either ixekizumab (80 mg every 4 or 12 weeks) or placebo for up to 60 weeks.
Patients treated with both dosing regimens of ixekizumab had significantly greater levels of skin clearance compared with those given etanercept or placebo at the 12-week endpoint. Skin clearance was measured by standard primary criteria for psoriasis studies: the Psoriasis Area and Severity Index (PASI) and the Static Physician Global Assessment (sPGA).
At week 12, at least a 75% reduction in the PASI score (PASI 75) was achieved by 78% to 90% of the patients treated with ixekizumab every 2 weeks or every 4 weeks. In addition, 31% to 41% of those patients achieved PASI 100 (clear skin) at week 12. In comparison, 5% to 7% of patients treated with etanercept in the UNCOVER-2 and -3 studies achieved PASI 100.
Statistically significant improvements in skin-clearance measures were observed in patients treated with ixekizumab as early as the first week compared with etanercept or placebo and continued through week 12. In the UNCOVER-1 study, high levels of response were maintained through 60 weeks of treatment.
Adverse events were comparable for patients receiving ixekizumab in the 12-week, randomized, controlled portion of all three studies. The overall rates and severities of adverse events observed were comparable with those for etanercept in the two active-comparator trials. The most frequently reported events (more than 5% across all three studies) were nasopharyngitis and injection-site reactions. Most injection-site reactions were mild, and most patients who experienced an injection-site reaction continued treatment with ixekizumab.
The medication is expected to be submitted for FDA review in the first half of 2015.
Ixekizumab is a monoclonal antibody with high affinity and specificity that binds to and neutralizes the pro-inflammatory cytokine interleukin-17A (IL-17A). In psoriasis, IL-17A plays a key role in driving excess keratinocyte proliferation and activation. Ixekizumab does not bind to cytokines IL-17B, IL-17C, IL-17D, IL-17E, or IL-17F. The treatment is administered via subcutaneous injection. It is also in clinical development for the treatment of psoriatic arthritis.
Psoriasis is a chronic, noncontagious autoinflammatory disease that occurs when the immune system sends faulty signals that speed up the growth cycle of skin cells. It is the most common inflammatory disease in the U.S., affecting as many as 7.5 million Americans. Psoriasis can occur on any part of the body and is associated with other serious health conditions, such as diabetes and heart disease.
The most common form of psoriasis — plaque psoriasis — appears as raised, red patches covered with a silvery white buildup of dead skin cells. Approximately 17% of psoriasis patients have moderate-to-severe plaque psoriasis.
Source: Eli Lilly; August 21, 2014.