BERLIN – In separate trials conducted in patients with hidradenitis suppurativa (HS), two biologics that inhibit the activity of interleukin-17A (IL-17A) and IL-17F were associated with highly encouraging rates of control.
One of the trials evaluated a nanobody inhibitor, sonelokimab, a molecule with a substantially smaller size than traditional monoclonal antibodies (40 kilodaltons vs. 150 kilodaltons). After 24 weeks of treatment, the most effective of the two study doses almost doubled the proportion of patients with complete resolution of draining tunnels (41.1% vs. 23.8%; P < .05) relative to placebo.
"I think the size of sonelokimab is important," Brian Kirby, MD, a consultant dermatologist at St. Vincent's Hospital, Dublin, said at the annual congress of the European Academy of Dermatology and Venereology. "We think the smaller size results in better penetration of inflamed tissue," he added, noting that penetration of abscesses, fistulae, and tunnels has been recognized in the past as a potential weakness of the larger monoclonal antibodies.
The other set of anti-17-A/F set of data were generated by a pooled 48-week maintenance from the BE HEARD I and II trials with bimekizumab. The 16-week data from these two trials were presented at the annual meeting of the American Academy of Dermatology earlier this year.
IL-17A/F trials
Both the 16-week phase 2 data with sonelokimab and the 48-week pooled phase 3 maintenance data with bimekizumab were presented as late-breakers at the EADV Congress.
In the sonelokimab trial, called MIRA, 234 adults with HS were randomized in a 2:2:2:1 ratio to one of the two experimental arms, placebo, or a reference arm with the tumor necrosis factor (TNF) inhibitor adalimumab. Nearly 64% had Hurley stage II HS.
The primary endpoint was a 75% or greater reduction in total abscesses and nodules with no increase in draining tunnel count (HiSCR75) from baseline. Dr. Kirby said that this is more rigorous than the HiSCR50 endpoint more commonly used in HS clinical trials. Treatments were administered every 2 weeks for the first 8 weeks of a planned follow-up of 24 weeks and then every 4 weeks thereafter.
At 16 weeks, according to the data Dr. Kirby presented, both doses of sonelokimab were more active than placebo, but Dr. Kirby reported that the lower dose performed better for most objective endpoints.
For example, the HiSCR75 was reached by 43.3% of those randomized to the 120-mg dose (P < .001 vs. placebo), 34.8% of those randomized to the 240-mg dose (P < .01), and 14.7% of those randomized to placebo.
For HiSCR50, response rates were 65.7%, 53.0%, and 27.9%, for the 120-mg, 240-mg, and placebo arms, respectively. Again, both the lower dose (P < .001) and the higher dose (P < .01) were significantly superior to placebo.
On the International Hidradenitis Suppurativa Severity Score System (IHS4), which counts nodules and abscesses, score reductions were 19.3, 14.5, and 7.9 for the lower dose, higher dose, and placebo, respectively, with a greater statistical advantage for the lower relative to the higher dose over placebo (P < .001 vs. P < .01).
However, patient-focused outcomes were not necessarily greater for the lower dose. For the patient-completed measure, the Numerical Rating Scale 50% reduction in skin pain (NRS50), the proportion of patients responding at 12 weeks was numerically greater for the 240-mg dose (41.3%) than with the 120-mg dose (32.0%), although both reached the same statistical advantage (P < .001) over the 4.3% who reached this level of response on placebo.
For the Dermatology Life Quality Index (DLQI) and the Patient Global Impression of Severity (PGI-S), improvements from baseline were similar for the lower and higher dose, although there was a modest numerical and statistical advantage for the higher dose over placebo (P < .001 vs. P < .01).
The HiSCR50 (57.6%) and HiSCR75 (36.4%) responses were both lower for those randomized to the TNF inhibitor adalimumab relative to sonelokimab, but the smaller number of patients in this arm prohibited a statistical comparison.
Although oral candidiasis was more common among patients receiving either dose of sonelokimab than placebo, these were of mild to moderate severity. Dr. Kirby said that there were no unexpected safety issues, and sonelokimab was generally well tolerated.
The results are encouraging, but Dr. Kirby acknowledged that data are now needed to confirm that resolution of tunnels and fistulae is greater with a nanobody inhibitor of IL-17A/F than other targeted therapies. Even if this is validated, he said studies are needed to prove that the small relative molecule size is the reason behind the benefits.
Forty-eight–week bimekizumab data
From the pooled BE HEARD I and BE HEARD II maintenance data, the major message is that the robust responses observed at 16 weeks versus placebo were maintained at 48 weeks. More than 75% of patients retained a HiSCR50 response and more than 55% achieved a HiSCR75 response at the 48-week follow-up. The durable response was also reflected in other measures, according to Christos C. Zouboulis, MD, PhD, director of the department of dermatology, Brandenburg Medical School, Neuruppin, Germany.
"Improvements in disease severity were seen over time," Dr. Zouboulis reported. "The majority of patients with severe HS at baseline shifted to mild to moderate disease according to the IHS4 classification."
To the degree that both sonelokimab and bimekizumab target IL-17A/F, these data are mutually reinforcing. Dr. Kirby said that there is a sizable body of data implicating IL-17A/F in driving HS, and the activity of inhibitors in support the clinical value of IL-17A/F suppression.
On Oct. 18, shortly after the EADV meeting concluded, the Food and Drug Administration approved bimekizumab for treating moderate to severe plaque psoriasis, the first approved indication in the United States. In the European Union, it was approved for psoriasis in 2021, and for psoriatic arthritis and ankylosing spondylitis in June 2023.
Dr. Kirby has financial relationships with more than 10 pharmaceutical companies, including MoonLake, which is developing sonelokimab and sponsored the MIRA trial. Dr. Christos, president of the European HS Foundation, has financial relationships with multiple pharmaceutical companies, including UCB, which makes bimekizumab and provided funding for the BE HEARD I and II trials.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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