乌鸦传媒

SAN DIEGO -- Patients suffering from moderate-to-severe plaque psoriasis treated with an investigational drug called bimekizumab achieved "rapid and substantial" clinical improvements in their condition, according to research presented here.

A team led by Kim Papp, MD, PhD, of Probity Medical Research in Waterloo, Ontario, found that at 12 weeks of treatment and at the highest bimekizumab dosing level, up to 86% of patients achieved a "clear" or "almost clear" response, and 60% achieved a Psoriasis Area and Severity Index (PASI) 100 response.

Papp presented the findings at the .

Bimekizumab is a humanized monoclonal lgG1 antibody that selectively neutralizes both IL-17A and L-17F -- the two key cytokines that drive the inflammation processes associated with plaque psoriasis, he explained.

"We know that IL-17A and its close sibling, IL-17F, engage the 17 receptor and in doing so drive inflammation. We've known for some time that by blocking 17A we're able to reduce that engagement and reduce the level of inflammation. Now we are investigating the opportunity of blocking both 17A and F with comparable degrees of suppression, and in doing so, further reducing the signal to the receptor and -- in principle -- further reducing [inflammation]."

With that in mind, Papp and his colleagues designed and carried out a phase II double-blinded, placebo-controlled, dose-ranging study (called BE ABLE 1) in order to evaluate the safety and efficacy of bimekizumab in moderate-to-severe plaque psoriasis.

A total of 250 patients were randomized in roughly equal numbers to receive bimekizumab at 64 mg, 160 mg, 160 mg with a 320 mg loading dose, 320 mg, 480 mg, or placebo every 4 weeks, for 12 weeks.

The primary endpoint was ≥90% reduction in PASI 90 at week 12. Secondary endpoints (PASI90 [week 8], PASI75 and PASI100 [week 12], and IGA [weeks 8 and 12]) and safety were also assessed.

Treatment with bimekizumab provided "significant" improvement in psoriasis severity, as measured by an Investigator's Global Assessment (IGA) 0/1 ("clear" or "almost clear") response at weeks 8 and 12, the researchers reported. The highest dosing groups had between 75% and 86% of patients achieving IGA 0 or 1.

The results were similar when measuring PASI 90 responses to bimekizumab, with 72-79% of patients in the highest dosing groups achieving PASI 90 at 12 weeks.

PASI 100 (complete resolution of the disease) at week 12 was achieved by 27.9%, 28.2%, 49.8%, 55.8%, and 60% of the patients in the five dosing groups (from lowest to highest). "And if we look at the slope of the curves extending to week 12, they suggest we haven't achieved the maximum response," Papp said.

When looking at absolute PASI over time "we see a significant reduction in median scores at week four," he added, noting that further improvements were seen at weeks 8 and 12.

As for dose-related safety risks at 12 weeks, the most frequently reported treatment-emergent adverse events were nasopharyngitis and upper respiratory tract infections.

Five patients receiving bimekizumab had grade 2 non-serious neutropenia reported, all of which resolved without having to interrupt treatment.

Fungal infections were reported by 4.3% of patients receiving bimekizumab, compared with none of the placebo patients. "Most of [the fungal infections] were superficial, and nothing we haven't seen before," Papp said.

"With dual neutralization of IL-17A and IL-17F we clearly saw there was a rapid onset of action. And in the highest dose groups we saw high levels of response, with 75% to 86% of patients achieving a result of clear/almost clear."

He also noted that the study resulted in 60% of patients in the highest dosing group achieving PASI 100: "We've seen 60% before, but this was 60% of patients achieving PASI 100 at 12 weeks."