AAD 2023 – UCB and Acelyrin take aim at hidradenitis suppurativa

Many groups view the skin disease hidradenitis suppurativa (HS) as a new opportunity to expand the reach of their autoimmune blockbusters, particularly since only one novel therapy is approved here. 

But that therapy is the now-off-patent Humira, so rivals will have to impress to persuade payers to switch away from Abbvie’s workhorse and its biosimilar versions. And phase 3 data presented at the weekend on both UCB’s Bimzelx and Acelyrin’s izokibep might not quite clear the bar.

UCB’s Be Heard I and Be Heard II trials, each in just over 500 patients with moderate to severe HS, pitted Bimzelx, an anti-IL-17A and IL-17F antibody, dosed every two and every four weeks, against placebo. The primary endpoint was achievement of hidradenitis suppurativa clinical response 50 (HiSCR50), defined as a reduction of at least 50% in the total abscess and inflammatory nodule count, with no increase in abscess or draining tunnel count, after four months’ treatment.

UCB said data from the two studies, presented on Saturday in a late-breaker at the American Academy of Dermatology’s annual meeting, showed statistically significant and clinically meaningful improvements over placebo, though in fact the monthly dose in Be Heard I did not achieve significance.

Improvements were also seen on the tougher measure HiSCR75, a secondary endpoint, at week 16, though again the less frequent dose in Be Heard I missed significance. 

The graph below compares these data to the pivotal HS data on Humira and Novartis’s Cosentyx. Novartis expects approval decisions on Cosentyx in HS in the US and EU this year. 

Notes: Humira data at 12wk, all others 16wk. Bimzelx efficacy data were presented using two analyses: one that imputes any new antibiotic usage as non-responders, and another that only imputes patients who take systemic antibiotics as rescue medication for HS as non-responders. Bimzelx’s primary endpoint analysis used the former, but the graph above uses the latter calculation since that is what Humira’s and Cosentyx’s pivotal studies used, so it makes for a fairer comparison.

On a cross-trial basis Bimzelx yielded better responses than Cosentyx – but the UCB project is still some way behind Humira's showing in the Pioneer II trial. UCB’s argument here will hinge on safety: the most common treatment emergent adverse events with Bimzelx were hidradenitis, oral candidiasis, headache and diarrhoea, whereas Humira’s label carries a boxed warning for serious infections and malignancy. 

UCB plans to file Bimzelx in moderate to severe HS this autumn.
 
Total clearance

Data on Acelyrin’s bispecific nanobody izokibep, presented at the same session, were also encouraging. The update came from the open-label part A portion of a phase 2b/3 HS study, which had already been toplined positive. 

After three months’ treatment, HiSCR50, HiSCR75, HiSCR90 and HiSCR100 – the last being total clearance of disease – were achieved by 71%, 57%, 38% and 33% of patients in part A. Without a placebo group, however, it is hard to compare these data against the other late-stage projects. Moreover, part A included just 30 patients. 

Izokibep was well tolerated, Acelyrin said, with no Candida infections. But injection site reactions were seen in 40% of patients, and led to two discontinuations. 

Based on these data, Acelyrin plans to begin a second phase 3 trial in HS. Meanwhile, the double-blind, placebo-controlled part B of the current trial is ongoing; the company has not disclosed when data might come, but judging by the study’s record on clinicaltrials.gov part B might read out this year. 

By then Cosentyx could be approved and Bimzelx filed. It will be some time before HS is as crowded a market as, say, psoriasis, but with a dozen or so candidates in phase 2 plenty of companies are looking for a piece of the action.