NEW ORLEANS — In two phase 3 trials, bimekizumab (Bimzelx), a monoclonal antibody targeting two types of interleukin-17 — IL-17A and IL-17F — reduced the abscess and inflammatory nodule count better than placebo in the chronic inflammatory skin condition hidradenitis suppurativa (HS), according to results presented together during a late-breaker session at the annual meeting of the American Academy of Dermatology.
“We are very excited to add this data to what we already have around IL-17 inhibition. This clearly validates this target for the control of HS,” reported lead investigator Alexa B. Kimball, MD, MPH, professor of dermatology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Dr Alexa Kimball
The trials, called BE HEARD I and BE HEARD II, enrolled 505 and 509 patients with HS, respectively. About 50% of patients in BE HEARD I and 60% of patients in BE HEARD II had Hurley stage 3 disease, which is the most severe of the three stratifications. The remainder were in Hurley stage 2. The mean duration of HS was 8.3 and 7.1 years, respectively.
Patients in both studies were randomized to one of four groups — either to a dosing regimen of 320 mg of bimekizumab administered by subcutaneous injection or to a placebo group. Both trials comprised double-blind 16-week initial and 32-week maintenance treatment periods.
In one experimental group, bimekizumab was given once every 2 weeks for the full course of the 48-week study (Q2W/Q2W). In another, patients started on the every-two-week schedule for 16 weeks and then were switched to every-4-week dosing (Q2W/Q4W). In the third group, patients started and remained on the every-4-week schedule (Q4W/Q4W). Patients in a fourth group started on placebo and switched at 16 weeks to the every-2-week bimekizumab schedule (placebo/Q2W).
The primary endpoint was HiSCR50, signifying a 50% reduction from baseline in abscess and inflammatory nodule count on the Hidradenitis Suppurativa Clinical Response (HiSCR) assessment tool. At 16 weeks, the initial Q2W dose in two of the groups outperformed the placebo in both BE HEARD I (47.8% vs. 28.7%) and BE HEARD II (52.0% vs. 32.2%). The response rates in the Q4W arm in BE HEARD I (45.3%) and BE HEARD II (53.8%) were also higher than the placebo, but the difference was only significant in BE HEARD II.
At 48 weeks, the proportion of patients with an HiSCR50 response climbed in all groups in both trials. The patterns were generally the same with slightly higher numerical responses among the groups that received the every-2-week dosing schedule relative to the every-4-week schedule.
In BE HEARD I at 48 weeks, the HiSCR50 response rate was about 60% for those who started and remained on every-2-week bimekizumab (Q2W/Q2W) or were switched at 16 weeks to every-four-week bimekizumab (Q2W/Q4W). For those who started and remained on every-4-week bimekizumab and the group started on placebo and switched to every-2-week bimekizumab, the response rates were 52.7% and 45.3%, respectively.
In BE HEARD II, the HiSCR50 response rates were higher in all groups, including the placebo, and the patterns of response were similar at 48 weeks. Most patients reached the HiSCR50 response — 79.8% (Q2W/Q2W), 78.4% (Q2W/Q4W), 76.7% (Q4W/Q4W), and 65.9 % (placebo/Q2W) of patients.
It is notable that, although there was rapid increase in the proportion of placebo patients reaching HiSCR50 after the switch at 16 weeks, there appeared to be an advantage at 48 weeks for starting on full dose bimekizumab over starting on placebo.
In this trial, patients were listed as nonresponders if they received antibiotics at any time and for any reason after randomization. This might have concealed an even greater benefit of bimekizumab, Kimball said, but the study design element was considered necessary to isolate the activity of the study drug.
“In future HS trials, it will be helpful to address the difficulty of handling the impact of antibiotics and pain medications [in assessing results],” Kimball said.
For HS patients, the secondary endpoint of HiSCR75 endpoint might be considered the most meaningful, according to Kimball. She said that this higher bar not only documents a higher level of efficacy but correlates with meaningful improvement in quality of life. In the two trials combined, more than 55% of patients on continuous bimekizumab achieved HiSCR75 at week 48 in the observed case analysis, according to a news release from biopharmaceutical company UCB.
In BE HEARD I, the HiSCR75 rates were 33.4% and 24.7% for the every-2 week and every 4-week bimekizumab doses, respectively. The 33.4% response was statistically superior to placebo (18.4%). In BE HEARD II, both the every-2-week dose (35.7%) and the every 4-week dose (33.7%) were superior to the 15.6% response in placebo patients.
The improvements in quality of life as measured with the Dermatology Life Quality Index (DLQI), reflected the changes in disease activity. Relative to about a 3-point reduction from baseline in the placebo groups of the two trials, the 5-point reduction for either the 2-week or 4-week bimekizumab groups in each clinical trial were highly significant, Kimball said.
Bimekizumab was relatively well tolerated, although it shares the increased risk for candidiasis observed with this agent when used in psoriasis and with other IL-17 inhibitors, such as secukinumab (Cosentyx), in general. The risk of candidiasis appeared to be dose related, but cases were generally mild and easily managed, according to Kimball. She noted that only three patients discontinued treatment for this reason. Discontinuations for a treatment-related adverse event overall was <4% at 16 weeks.
This is only the third phase 3 trial ever completed in patients with HS. In fact, Kimball has led all of the phase 3 trials so far, including clinical studies of adalimumab (Humira), published in 2016, and of secukinumab, published earlier this year. All were positive studies.
“This is amazing news for our patients,” Kimball said. HS remains a challenging disease even with a growing number of options showing benefit in large studies, she said, and the high rates of response, particularly at the level of HiSCR75, “is a huge milestone for what we can achieve.”
Her assessment was echoed by other experts, including Christopher J. Sayed, MD, an associate professor of dermatology at the University of North Carolina, Chapel Hill, who publishes frequently about this disease.
“It is incredibly exciting to see the strong phase 3 data on bimekizumab, particularly the deep responses at the HiSCR75 in a major of patients after the first year,” he said.
Importantly, he does not see the growing array of treatment options as necessarily competitive for a disease with heterogeneous manifestations and variable responses to any one agent.
“While this may be a major step forward, it will still be critical to see more drugs come along for those who do not respond fully enough or have comorbidities that prevent the use of IL-17 and TNF antagonists,” he said.
Kimball reports financial relationships with AbbVie, Janssen, Kymera, Lilly, Novartis, Pfizer, and UCB. Sayed reports financial relationships with AbbVie, InflaRx, and UCB.
American Academy of Dermatology (AAD) 2023 Annual Meeting:
Late-breaking Research Session S042. Presented March 18, 2023.
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