What is the BE ABLE Studies?
Global biopharmaceutical company recently presented results from their Phase 2b BE ABLE extension study of bimekizumab in patients with moderate-to-severe chronic plaque psoriasis, which shows nearly all BE ABLE 1 responders completing 60 weeks of bimekizumab treatment maintained complete or almost complete skin clearance. Bimekizumab potentially and selectively neutralizes IL-17F in addition to IL-17A, two key cytokines driving inflammatory processes. The findings were presented at a late breaker session at the American Academy of Dermatology Annual Meeting (AAD) in Washington, DC reports UCB in PR News Wire.
Summary of Findings
Despite recent advances in psoriasis therapies, patients still have profound unmet needs according to industry sponsor UCB’s press release.
Andrew Blauvelt, MD, MBA and investigator in the trial and President of Oregon Medical Research Center in Portland, Oregon noted “the long-term results observed in the BE ABLE 2 Phase 2b study suggest the meaningful difference that IL-17F inhibition, along with IL-17A inhibition can make psoriasis patients who need significant, long-term skin clearance.” He continued “the results add to a growing body of evidence supporting the molecule’s unique dual neutralization of both IL-17A and IL-17F cytokines across multiple inflammatory diseases, suggesting exciting potential.”
In the BE ABLE 1 trial, up to 79% of patients achieved at least 90% skin clearance (PAS190) as soon as week 12, based on dose range of 64mg, 160mg, 160mg with a 320mg loading dose, 320mg, or 480mg, administered every four weeks. Among these BE ABLE 1 responder, defined as achievement of PAS190 at week 12, 80-100% maintained the rigorous PAS190 measure for up to an additional 48 weeks based on a dose range of 160mg or 320mg, administered every 4 weeks, in the BE ABLE 2 extension study. Further, 70-83% and 78-100% of BE ABLE 1 responders maintained PASI100a and the Investigator’s Global Assessment of response, respectively. The safety profile was consistent with previous studies, with no new safety findings observed. The most frequent treatment-emergent adverse events were oral candidiasis and nasopharyngitis. No cases of suicidal ideation/behavior, major adverse cardiac events, or inflammatory bowel disease were reported.
What is Psoriasis?
Psoriasis is a chronic, immune-mediated inflammatory disease associated with prominent skin manifestations that affects approximately 1–3% of the population, or about 125 million people worldwide, although rates appear to vary by ethnicity, and estimates are sensitive to determination method. Psoriatic arthritis occurs in up to 41% of patients with psoriasis, and is typically characterized by inflammation, pain and swollen joints.
Unmet needs remain in the treatment of psoriasis. A population-based survey identified that approximately 30% of psoriasis patients reported that their primary goals of therapy, including keeping symptoms at bay, reducing itching, and decreasing flaking were not met with their current treatment. Failure to achieve or retain complete and lasting disease resolution across the multiple manifestations of psoriatic disease, including joints and other musculoskeletal symptoms, negatively impacts risk of comorbidities, disease progression and quality of life, which is likely multifactorial.
What is Bimekizumab?
Bimekizumab is an investigational novel humanized monoclonal IgG1 antibody that potently and selectively neutralizes both IL-17A and IL-17F, two key cytokines driving inflammatory processes. IL-17A and IL-17F have similar pro-inflammatory functions and independently cooperate with other inflammatory mediators to drive chronic inflammation and damage across multiple tissues.
Previous early phase clinical studies in psoriasis and psoriatic arthritis have suggested that bimekizumab’s unique dual neutralization of both IL-17A and IL-17F may provide a new targeted approach for the treatment of immune-mediated inflammatory diseases. Preclinical results in disease-relevant cells have shown that neutralizing IL-17F in addition to IL-17A reduces skin and joint inflammation, as well as pathological bone formation to an extent greater than inhibition of IL-17A alone.
BE ABLE Studies
BE ABLE 1 is a multi-center, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of bimekizumab compared with placebo in adult patients with moderate-to-severe chronic plaque psoriasis. In the 12-week BE ABLE 1 study, bimekizumab provided rapid, substantial clinical improvements in patients. After the initial 12-week treatment period, eligible patients enrolled in the Phase 2b extension study (BE ABLE 2), which assessed safety and efficacy of subcutaneous bimekizumab administered every four weeks for an additional 48 weeks. For those not enrolling in the extension study, a safety follow-up visit was conducted 20 weeks after the last dose of study medication.
BE ABLE 1 included 250 patients with chronic plaque psoriasis with an affected body surface area of at least 10% and PASI of at least 12. Patients were randomized into six dosing regimens to receive either placebo or bimekizumab every four weeks subcutaneously. Randomization was balanced across treatment groups.
BE ABLE 2 included 217 responders and non-responders from BE ABLE 1. Responders receiving placebo or bimekizumab 64mg, 160mg, 160mg (320mg loading dose [LD]) remained on the same dose. Non-responders, defined as <PASI90 at week 12, were reassigned from placebo/bimekizumab 64mg to 160mg, or 160mg/160mg (LD) to 320mg. Patients previously receiving bimekizumab 320mg/480mg received 320mg.
PASI is a score used by health care professionals to express the severity of psoriasis as measured by body surface area affected by the disease and severity of lesions. It is widely used to assess the skin improvement of people receiving treatment for psoriasis, particularly in clinical trials. In BE ABLE, efficacy was measured by the proportion of people who achieved a 90% improvement (PASI90, the primary efficacy variable) at week 12. By comparison, most previous trials in psoriasis have used the proportion of people who achieve a 75% improvement in the skin affected (PASI75), as the primary threshold for evaluating psoriatic skin clearance.
The secondary efficacy variables assessed in BE ABLE were Investigator’s Global Assessment of response (IGA) defined as clear or almost clear skin with at least 2 category improvement from baseline at week 8 and at week 12, PASI90 response at week 8, PASI75 response at week 12, and PASI100 response at week 12.