Phase II data, published in the New England Journal of Medicine ( NEJM ), have showen that Ixekizumab, an anti-IL-17 monoclonal antibody, met its primary endpoint in patients with moderate-to-severe plaque psoriasis, with significantly more patients achieving at least a 75% improvement in Psoriasis Area and Severity Index ( PASI ) scores from baseline ( PASI 75 ) compared with placebo at week 12.
PASI score represents a combined assessment of overall skin lesions ranging from 0 for no psoriasis to 72 for the worst possible psoriasis in a patient and is a standard measure of skin disease severity in clinical trials in psoriasis.
A PASI 75 response in a patient represents a 75% reduction of PASI scores from baseline.
In the 142-subject study, significantly more patients achieved a PASI 75 response in the 150 mg ( 82% ), 75 mg ( 83% ) and 25 mg ( 77% ) Ixekizumab groups compared with placebo ( 8%, p less than 0.001 ) at week 12. The 10 mg dose ( 29% ) did not separate from placebo at week 12.
Secondary endpoints included an evaluation of the percentage of patients achieving at least 90% and 100% improvement in PASI ( PASI 90 or PASI 100 ) at week 12.
In patients treated with Ixekizumab, the percentages of patients achieving a PASI 90 response were 71% ( 150 mg ), 59% ( 75 mg ) and 50% ( 25 mg ), which were significantly higher than with placebo ( 0% ).
PASI 100 responses were significantly better at the 150 mg dose ( 39% ) and 75 mg dose ( 38% ) when compared with placebo ( 0% ). PASI 100 responses at the 25 mg ( 17% ) and 10 mg doses ( 0% ) were not significantly greater than placebo, nor was the PASI 90 response at the 10 mg dose ( 18% ).
PASI 75 response was significantly better than placebo as early as week 2 at the highest dose, and significant differences from placebo in PASI scores were seen as early as week 1 at the two highest doses and by week 4 for the remaining two doses. Differences from placebo were sustained to week 20 in both PASI 75 responses and PASI scores.
Skin disease severity also was evaluated by static Physician Global Assessments ( sPGA ), with patients having a score of 3-5 ( moderate to severe disease ) at baseline. Significantly more patients treated with Ixekizumab achieved an sPGA score of 0 ( clear of disease ) or 1 ( minimal disease ), when compared with placebo at week 12.
The percentage of patients achieving an sPGA 0 or 1 score were 71% ( 150 mg ), 72% ( 75 mg ), 70% ( 25 mg ) and 25% ( 10 mg ) compared with 8% ( placebo ), with the highest three doses being significantly higher than placebo.
The percentage of patients achieving an sPGA score of 0 at week 12 were 46% ( 150 mg ), 38% ( 75 mg ), 20% ( 25 mg ), 7% ( 10 mg ) and 0% ( placebo ), again with the highest three Ixekizumab doses being significantly higher than placebo.
Approximately 40% of patients in the two highest dose groups had complete clearance of psoriasis plaques on the skin, as reflected by a reduction in the PASI score by 100% or an sPGA score of 0 at 12 weeks.
In addition, significant reductions in mean Nail Psoriasis Severity Index ( NAPSI ) and Psoriasis Scalp Severity Index ( PSSI ), which evaluate disease in the difficult-to-treat areas of nails and scalp, respectively, were seen at the two highest Ixekizumab doses compared with placebo at week 12 ( NAPSI: 150 mg [ -49.3% ], 75 mg [ -57.1% ], placebo [ +6.8% ]; PSSI: 150 mg [ -84.8% ], 75 mg [ -94.8% ], placebo [ -30.5% ] ).
The frequency of adverse events in both the combined Ixekizumab groups and in the placebo group was 63%, with the most common adverse events observed being nasopharyngitis ( inflammation of the nasal passages and of the upper part of the pharynx ), upper respiratory infection, injection site reactions and headache.
There were no serious adverse events reported. Infections occurred in 33% ( n=38 ) of subjects receiving Ixekizumab and 26% ( n=7 ) receiving placebo.
No dose-related trends in infections or other adverse events were observed.
Four patients ( one in the placebo group, two in the 10 mg group and one in 25 mg group ) discontinued the study due to adverse events.
According to Craig Leonardi, at the Saint Louis University School of Medicine, these data suggest Ixekizumab may be an effective treatment for patients with chronic moderate-to-severe plaque psoriasis and could represent a new treatment approach for patients with this condition.
Psoriasis is the most prevalent chronic, autoimmune disease of the skin in the United States, affecting about 7.5 million people. It occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells. Approximately 17% of psoriasis patients have moderate-to-severe plaque psoriasis.
Ixekizumab is a humanized monoclonal antibody that binds to and neutralizes actions of the pro-inflammatory cytokine, interleukin-17A ( IL-17A, also called IL-17 ), and is administered via subcutaneous injection. ( Xagena )
Source: Lilly, 2012