BIMZELX (bimekizumab), a monoclonal IgG1 antibody, selectively inhibits interleukin (IL)-17F in addition to IL17A. The European Medicines Agency (EMA) approved Bimekizumab in June 2023 for the treatment of adults with active psoriatic arthritis and adults with active axial spondyloarthritis (axSpA), including non-radiographic axSpA (nr-axSpA) and ankylosing spondylitis. Later, in December 2023, it received approval in Japan for the treatment of psoriatic arthritis, nr-axSpA, and ankylosing spondylitis. In the US, it is only approved for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. 

Vimpat (2022) and CIMZIA (2024), the patent cliffs for the highest-selling drugs, are something that UCB has been diligently planning for by investing in both R&D and M&A.  As of right now, CIMZIA is the biggest medication in the UCB portfolio, exhibiting steady growth and steady performance.  BIMZELX has the potential to be UCB's next best-selling medication in highly competitive markets like psoriasis and psoriatic arthritis, as well as unexplored ones like Hidradenitis Supprativa.  BIMZELX could become the commercial successor of CIMZIA. UCB Biopharma submitted many abstracts for bimekizumab in various indications at EULAR 2024. 

Axial Spondyloarthritis: 

UCB submitted many abstracts at EULAR 2024 highlighting evidence on bimekizumab in axial spondyloarthritis (POS0058, POS0805, POS0806, LBA0003, and POS0215). Data shows that axial spondyloarthritis patients with non-radiographic and radiographic axSpA were able to sustainably suppress inflammation over a 2-year period. These patients also reported sustained improvements in symptoms that significantly impact their daily lives. One of the long-term therapeutic goals is to stop the structural changes of axSpA. According to late-breaking data, most patients treated with bimekizumab for radiographic axial spondyloarthritis did not show any improvement in their spine radiography over a 2-year period.

#POS0215: Five-year efficacy and safety results of bimekizumab in BE AGILE and its open-label extension (OLE)

BE AGILE (NCT02963506) was a Phase IIb clinical trial that lasted 12 weeks and was double-blind and placebo-controlled. After that, participants received bimekizumab 160 or 320 mg every 4 weeks (Q4W) during a dose-blind phase that ended at week 48. After week 48, patients who met the eligibility requirements for participation in the Open Label Extension study (OLE; NCT03355573; BE AGILE 2), were all given bimekizumab 160 mg Q4W until week 256. Approximately 97.7% (296/303) of the randomized BE AGILE patients started the dose-blind phase, and 87.5% (265/303) completed up to week 48. Seventy-nine percent (202/255) of the 84.2% (255/303) of patients who started the OLE at week 48 and had ≥1 bimekizumab dosage completed by week 256. 

Clinical efficacy was sustained, with 51.7% achieving Assessment of SpondyloArthritis international Society 40% response (ASAS40), 49.3% achieving AS Disease Activity Score (ASDAS) <2.1 at OLE entry, and 49.7% and 41.6% maintaining these responses at Week 256, respectively. 

The OLE full analysis set (FAS) showed similar results, with 59.8% achieving ASAS40 and 57.3% achieving ASDAS <2.1 at Week 48 and 59.0% and 66.0% maintaining these responses at Week 256, respectively. Improvements in disease activity, physical function, and quality of life observed by Week 48 were sustained or further improved by Week 256. Mean reductions in ASDAS and BASDAI from baseline to Week 48 were maintained or decreased further by Week 256. Additionally, improvements in BASFI and ASQoL from baseline to Week 48 were sustained through Week 256. According to the company, this is the first report presenting NRI ASAS40 data for up to five years in patients with ankylosing spondylitis treated with novel therapies.

#LBA0003: Minimal spinal radiographic progression in axSpA patients after 2 Years of bimekizumab treatment in Phase III OLE Study (NCT04436640; BE MOVING) Results 

Minimal spinal radiographic progression and a high proportion of non-progressors, including those with baseline spinal damage, were demonstrated at two years of treatment with bimekizumab in patients with r-axSpA. At Week 104, 71.2% of patients with r-axSpA had an available modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). In these patients, the mean mSASSS score at baseline was 7.3, and the change from baseline (CfB) at Week 104 was 0.3. Most patients showed no spinal radiographic progression at Week 104 with bimekizumab treatment. The proportion of non-progressors at Week 104, defined as mSASSS CfB ≤0.5, was 85.3%. When defined as mSASSS CfB <2, the proportion of non-progressors was 92.1%, including 83.1% of patients with existing structural damage (mSASSS ≥2) at baseline. None of the assessed potential predictive factors were significantly associated with an increased likelihood of spinal radiographic progression.

The company presented three abstracts, POS0058, POS0805, and POS0806, featuring data from various endpoints of two Phase III BE MOBILE 1 (NCT03928704) and BE MOBILE 2 (NCT03928743) studies.

#POS0058: Bimekizumab's Transformative Impact on Sacroiliac Joint Lesions: 52-Week Findings from BE MOBILE Phase III Studies

From two parallel Phase III studies, the company demonstrated the impact of bimekizumab on sacroiliac joint (SIJ) inflammation and structural lesions across the full spectrum of axSpA up to Week 52. Dual inhibition of IL-17A and IL-17F with bimekizumab over 52 weeks significantly improved MRI-detected inflammation, reduced erosions, and increased backfill and fat in the SIJ of patients with nr-axSpA and r-axSpA, suggesting potential tissue repair.

#POS0805: Long-Term Symptom Relief with Bimekizumab in Axial Spondyloarthritis: 2-Year Phase III Study Results

Treatment with bimekizumab resulted in consistent and sustained improvements in spinal pain, morning stiffness, and fatigue among patients with r-axSpA and nr-axSpA. The data showed that more than 50% of patients achieved total and nocturnal spinal pain scores below 4, with over 25% and 35% reaching scores below 2, respectively, from week 52 through week 104. Additionally, a significant percentage of patients, exceeding 50%, were considered responders for FACIT-Fatigue, indicating improved fatigue levels throughout the study period. These findings highlight the enduring benefit of bimekizumab on key clinical symptoms that are highly impactful on patients' daily lives. The consistency of these results across both nr-axSpA and r-axSpA patient groups underscores the broad effectiveness of bimekizumab in addressing the diverse manifestations of axSpA.

#POS0806: Sustained Long-Term Efficacy and Safety of Bimekizumab in Axial Spondyloarthritis: 2-Year Phase III Study Results

Over two years, bimekizumab consistently maintained ASAS40 response rates and achieved low disease activity in a significant proportion of patients, highlighting its sustained therapeutic benefit. The suppression of inflammation, as evidenced by hs-CRP levels, further underscores bimekizumab's effectiveness in managing axSpA. Regarding safety, while most patients experienced treatment-emergent adverse events, the incidence of serious events was notably low, with no major safety signals observed. Hepatic events and fungal infections were manageable, with minimal impact on treatment continuity. These findings reinforce bimekizumab's favorable risk-benefit profile and support its continued use as a valuable therapeutic option for axSpA across the disease spectrum.

Conclusion: The long-term safety profile of bimekizumab in patients with axSpA remained consistent with earlier findings, with no new safety concerns identified. Clinical efficacy, demonstrated by improvements in signs and symptoms, disease activity, physical function, and health-related quality of life, was sustained for up to five years of bimekizumab therapy. 

KOL Insight

“So, generally, when we are looking at 5-year, longitudinal studies on a new compound, what is more, interesting for clinicians is the safety, to see whether the drug is really safe for the long term, because 12 weeks and 48 weeks may or may not tell you much about the safety. The safety up to week 256 for exposure to bimekizumab in patients with active ankylosing spondylitis showed that there were no new safety signals. We are aware that the IL-17 cytokine is important in our daily life for the prevention of fungal infections, especially candida infections.”

• MD, professor of medicine in the Division of Arthritis and Rheumatic Diseases at Oregon Health and Science University

 

Psoriatic Arthritis

UCB presented two abstracts, POS0969 and POS0961, of bimekizumab showcasing efficacy data for psoriatic arthritis. These abstracts included data from BE OPTIMAL (NCT03895203) BE COMPLETE  (NCT03896581), and  BE VITAL (open-label extension; NCT04009499) studies. 

 

When treating psoriatic arthritis, remission and minimal disease activity (MDA) are important goals. About 50% of patients treated with bimekizumab during a two-year period sustained MDA and remission, according to the first two-year bimekizumab results in psoriatic arthritis from the Phase II trials, BE OPTIMAL and BE COMPLETE (#POS0969). Moreover, many patients who achieved ACR50 and PASI90 at Week 16 continued to respond at Week 52, with a significant number maintaining response for the duration of the research (#POS0961).

POS0969: Long-Term Minimal Disease Activity and Remission in Psoriatic Arthritis with Bimekizumab: 2-Year Phase III Study Results

When treating psoriatic arthritis, remission and minimal disease activity (MDA) are important goals. The data from BE OPTIMAL (NCT03895203) and BE COMPLETE  (NCT03896581) trials show that bimekizumab-treated patients with psoriatic arthritis sustained meaningful improvements in achieving MDA and Disease Activity in Psoriatic Arthritis (DAPSA) remission or low disease activity (REM+LDA) responses over two years. This was consistent across patients previously treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and those naïve to bDMARDs. Achieving MDA by week 52 (bDMARD-naïve 54.8%; TNFi-IR [inadequate response/intolerance to tumor necrosis factor inhibitors] 46.4%) in bimekizumab-randomized individuals was sustained to week 104/88 in both study populations (bDMARD-naïve 52.4%; TNFi-IR 46.1%). 

Notably, bimekizumab led to substantial and sustained improvements in various MDA components, including joint and skin outcomes, as well as patient-reported measures like pain and physical function. These findings underscore bimekizumab's efficacy in addressing both clinical and patient-reported aspects of PsA, highlighting its potential as a valuable treatment option for patients across different disease backgrounds and symptom profiles. 

POS0961: Bimekizumab Maintains Efficacy through 52 Weeks in Active Psoriatic Arthritis: Phase III Study Results 

The data from patients randomized to bimekizumab in both bDMARD-naïve and TNFi-IR groups demonstrate durable efficacy responses over time. High proportions of patients achieving ACR50 and PASI90 at Week 16 maintained these responses at Week 52, with many not losing response throughout the study period. 

At week 16, 43.9% of bDMARD-naïve patients and 43.4% of TNFi-IR patients attained ACR50; at week 52, 86.8% of bDMARD-naïve patients and 80.2% of TNFi-IR patients maintained responses. Similar results were seen in patients with BL psoriasis affecting ≥3% of body surface area. At week 16, 61.3% of bDMARD-naïve and 68.8% of TNFi-IR patients attained PASI90. At week 52, 82.7% of bDMARD-naïve and 88.4% of TNFi-IR patients continued to respond. The majority of patients did not lose response at any visit to week 52. Specifically, 58.2% of bDMARD naïve and 63.8% of TNFi-IR patients did not lose ACR50 response, while 72.9% of bDMARD naïve and 79.3% of TNFi-IR patients did not lose PASI90 response at any visit to week 52.

Similarly, ACR70 and PASI100 responders showed sustained efficacy, with a significant percentage maintaining these responses and not losing them up to Week 52. At week 16, 26.6% of TNFi-IR and 24.4% of bDMARD naïve patients attained ACR70; of those, 82.9% of TNFi-IR and 83.1% of bDMARD naïve patients maintained ACR70 response at week 52, and 8.6% of bDMARD naïve and 57.7% of TNFi-IR patients never lost response to week 52. 47.5% of bDMARD-naïve and 58.5% of TNFi-IR points achieved PASI100 at week 16; of those, 79.6% of bDMARD-naïve and 84.5% of TNFi-IR points kept the response at week 52, while 61.2% of bDMARD-naïve and 73.8% of TNFiIR points never lost response to week 52. Similar patterns were observed for ACR50 responders from Week 16 who never lost their ACR50 or ACR20 response by Week 52. 

 

These findings highlight bimekizumab's ability to maintain robust efficacy across joint and skin outcomes, regardless of prior bDMARD use. The consistency of response maintenance underscores the durable improvement provided by bimekizumab in treating psoriatic arthritis, offering promising outcomes for patients seeking long-term disease control.

Conclusion: Bimekizumab treatment consistently maintained robust efficacy in PsA patients, demonstrating durable improvement in joint and skin outcomes over two years, irrespective of prior bDMARD use. These findings highlight bimekizumab's effectiveness in sustaining disease control and improving patient-reported outcomes, emphasizing its value as a long-term treatment option for PsA.

KOL Insight:

“Bimekizumab-treated patients achieved sustained MDA responses and DAPSA improvements from baseline up to 2 years, regardless of prior DMARD use. Improvements were observed across all patient-reported and most clinical components of MDA. Robust improvements were observed in joint and skin outcomes. Bimekizumab was well tolerated, with no new safety signals observed.”

 

• Rheumatologist, UK