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Biotech Med Ixekizumab (Taltz) Wins FDA Nod for Treatment of Plaque Psoriasis
The FDA has approved ixekizumab (Taltz, Eli Lilly) injection 80 mg/mL for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. Ixekizumab is designed to specifically target interleukin-17A, a protein that plays a role in driving underlying inflammation in psoriasis.
Psoriasis is a chronic immune disease that affects approximately 7.5 million Americans, approximately 20% of whom have moderate-to-severe plaque psoriasis. The exact cause of psoriasis is unknown, although genetics and environmental factors are known to be involved in the development of the disease.
The FDA’s approval of ixekizumab was based on findings from a phase 3 trial program involving more than 3,800 patients with moderate-to-severe plaque psoriasis in 21 countries. This number includes patients who began the trial on ixekizumab, placebo, or an active comparator (U.S.-approved etanercept [Enbrel, Amgen]).This clinical program included three double-blind, multicenter studies—UNCOVER-1, UNCOVER-2, and UNCOVER-3. All three studies evaluated the safety and efficacy of ixekizumab (80 mg every two weeks after a 160-mg starting dose) compared with placebo after 12 weeks of treatment. UNCOVER-2 and UNCOVER-3 included an additional comparator arm in which patients received etanercept (50 mg twice a week) for 12 weeks. UNCOVER-1 and UNCOVER-2 also evaluated response rates with ixekizumab during the maintenance period through 60 weeks.
In these studies, the coprimary efficacy endpoints at 12 weeks were a 75% improvement in the composite Psoriasis Area Severity Index score (PASI-75) and a static Physician’s Global Assessment (sPGA) score of 0 or 1, with at least a two-point improvement from baseline. PASI measures the extent and severity of psoriasis by assessing the average redness, thickness, and scaliness of skin lesions (each graded on a scale of 0 to 4), weighted by the body surface area of involved skin, whereas the sPGA is the physician’s assessment of severity of a patient’s psoriasis lesions overall at a specific point in time. The sPGA is a required measure the FDA uses to evaluate the effectiveness of treatment.
In all three studies, 87% to 90% of patients treated with ixekizumab demonstrated a significant improvement in their psoriasis plaques (PASI-75) at 12 weeks. In addition, 81% to 83% of patients treated with ixekizumab achieved an sPGA score of 0 or 1. Most of the patients treated with ixekizumab (68% to 71%) achieved virtually clear skin (PASI-90), and 35% to 42% of the patients experienced complete resolution of their psoriasis plaques (PASI-100 and an sPGA score of 0). Among the patients treated with placebo, 7% or fewer achieved PASI-75; 7% or fewer achieved an sPGA score of 0 or 1; 3% or fewer achieved PASI-90; and 1% or fewer achieved PASI-100 and an sPGA score of 0.
In the UNCOVER-1 and UNCOVER-2 trials, of the patients who responded to ixekizumab (an sPGA score of 0 or 1 and at least a two-point improvement from baseline) at 12 weeks, 75% maintained that response at the 60-week endpoint.
Ixekizumab was also statistically superior to etanercept at all skin-clearance levels, including PASI-75 and an sPGA score of 0 or 1 at 12 weeks. In an integrated analysis of the U.S. sites in the two active-comparator studies (UNCOVER-2 and UNCOVER-3), the respective response rates for ixekizumab and etanercept were 87% versus 41% for PASI-75, and 73% versus 27% for an sPGA score of 0 or 1.
Ixekizumab may increase the risk of infection. Patients treated with ixekizumab had a higher rate of infections compared with those treated with placebo (27% vs. 23%, respectively). Upper respiratory tract infections, oral candidiasis, conjunctivitis, and tinea infections occurred more often in patients treated with ixekizumab than in those given placebo.
In the UNCOVER-2 and UNCOVER-3 trials, the rates of serious adverse events during the controlled induction period (weeks 0 to 12) were 2.0% for ixekizumab and 0.7% for etanercept, and the rates of discontinuation because of adverse events were also 2.0% and 0.7%, respectively. The rates of infections were 26% for ixekizumab and 18% for etanercept, and the rate of serious infections was 0.3% for both treatment groups.
Ixekizumab will be available in the U.S. beginning in the second quarter of 2016.
Source: Eli Lilly; March 22, 2016.