麻豆传媒

Researchers have now reported full 52-week results from the two parallel phase III trials of the interleukin-17 (IL-17) blocker bimekizumab in axial spondyloarthritis (axSpA), following interim data published early this year, with strong efficacy demonstrated.

But when or whether the product will reach the U.S. market remains anyone's guess.

With improvement of at least 40% in Assessment of SpondyloArthritis International Society ratings (ASAS40) serving as the primary efficacy endpoint, more than 60% of patients were classified as responders after 1 year of continuous treatment with bimekizumab, according to Xenofon Baraliakos, MD, PhD, of Ruhr University Bochum in Herne, Germany, and colleagues.

And patients initially randomized to placebo but switched to the active drug after week 16 achieved nearly identical responses by week 52, the researchers .

In a January publication, the same group reported a similar pattern of results at week 24. For some subgroups, response rates continued to climb during the subsequent 28 weeks; no declines in response rates were seen.

Bimekizumab is unique in targeting the two IL-17 subspecies designated A and F. As Baraliakos and colleagues explained, "[a]lthough IL-17A is considered to be more biologically active, IL-17F is enriched in the skin and synovial tissue of patients with spondyloarthritis," making it an attractive secondary target for drug therapy. Bimekizumab therefore differs from biologics such as secukinumab (Cosentyx) that inhibit IL-17A only, and is hoped to be more effective as a result.

The drug's developer, UCB Pharma, initially focused on plaque psoriasis for marketing authorization, winning approvals in numerous countries around the world, but the FDA balked last year after inspectors identified problems at UCB's manufacturing plant in Belgium. UCB had hoped to have the issue resolved by now, but that the timeline was still uncertain, despite an apparently successful re-inspection in April.

UCB has also gained approvals for bimekizumab in psoriatic arthritis and, in June, the European Union granted authorization in non-radiographic axSpA and also for ankylosing spondylitis, both as second-line treatment.

Study Details

The two axSpA registration trials, dubbed and , enrolled a total of about 600 patients with clinical axSpA (i.e., lacking clear imaging evidence of the disease) and radiographic axSpA, respectively. Participants were randomized 1:1 in BE MOBILE 1 and 2:1 in BE MOBILE 2 to the active drug or placebo, without other background medications. Bimekizumab was administered by injection every 4 weeks. Treatment lasted 16 weeks, at which point patients were evaluated for the primary and secondary endpoints. An open-label extension then followed, during which the bimekizumab groups continued as before and the placebo groups were switched to the active drug.

Mean patient age was about 40, with a predominance of men. Roughly 15% had previously used tumor necrosis factor (TNF) inhibitors. Disease activity ratings at baseline averaged 3.7 on the Ankylosing Spondylitis Disease Activity Score (ASDAS) and approximately 6.6 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

Scores on these secondary measures also paralleled those for ASAS40. The proportion of patients achieving "major improvement" in ASDAS, for example, rose from 35% at week 16 to 47% at week 52 for those remaining continuously on bimekizumab. Some 37% of the original placebo group, after starting bimekizumab after week 16, saw major improvement by week 52. The same pattern was reported for achievement of 50% improvement in BASDAI scores.

Perhaps more important than these efficacy data, however, was the safety profiling for the extra months of treatment. For sure, more adverse events developed after the 16-week randomized and blinded phase was over. During that initial period, only five severe treatment-emergent adverse events (TEAEs) were recorded. Over the following 36 weeks, however, investigators counted 18 more.

Discontinuations due to TEAEs remained uncommon, though: 3% of patients with nonradiographic disease and 5% of those with radiographic axSpA quit the study. Most such events were relatively minor, such as nasopharyngitis and headache.

Infections, however, were a concern. Over the full yearlong studies, 2% of participants had serious infections of any kind, 8% experienced oral candidiasis, and more than 15% had fungal infections of any kind. Some 11% had "hepatic events." However, neutropenia was rare, afflicting only about 1% of patients, and there were few or no major cardiovascular events or malignancies.

Overall, Baraliakos and colleagues concluded, the safety data were "consistent with previous evidence" from bimekizumab's other clinical trials, including those in psoriasis as well axSpA.

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