Several new potential therapies for hidradenitis suppurativa are coming down the pike.

Several new potential therapies for hidradenitis suppurativa (HS) are coming down the pike, according to research presented at the 2023 American Academy of Dermatology (AAD) Annual Meeting in New Orleans. 

Acelyrin, Inc.'s Izokibep led to HiSCR response at 12 weeks, including HiSCR100 responses in 33 percent of patients with moderate-to-severe HS, according to data from an open-label Part A of Phase 2b/3 clinical trial. 

The double-blind, placebo-controlled Part B of this Phase 2b/3 trial is ongoing, and based on the Part A results, ACELYRIN plans to accelerate the initiation of the second Phase 3 trial in HS.

Izokibep is a unique, antibody mimetic, interleukin-17A (IL-17A) inhibitor designed to overcome the limitations of monoclonal antibodies. High potency and small molecular size – about 1/10 the size of a monoclonal antibody –enable izokibep to reach high drug exposure levels, improved tissue penetration, and extended plasma half-life, the company states.

In the trial conducted at multiple sites in the United States, participants with Hurley Stage II and III disease received 160 mg of izokibep dosed subcutaneously every week. Results as observed at week 12 showed 71 percent of participants achieved HiSCR50, 57 percent achieved HiSCR75, 38 percent achieved HiSCR90 and 33 percent achieved HiSCR100.

Izokibep was generally well-tolerated with localized mild-to-moderate injection site reactions being the most common adverse event. There were no candida events reported through week 12.

“HS has always been with us,” says Kim Papp, MD, PhD, FRCPC, a dermatologist in Waterloo, Ontario, Canada, in an interview with DermWire. He presented the Izokibep study results at the AAD meeting. “It is a horrible disease that can afflict young and middle-aged adults and can be that much more impactful during these prime years.”For many years, dermatologists would just use whatever seemed to work to treat HS, and nothing worked well, he said.

But that was then.

The TNF blocker adalimumab's (Humira) approval by the US Food and Drug Administration for HS in 2015 opened the floodgates. "It said there is hope and we have at least a little bit of insight into what is at play on the inflammatory side of things," Dr. Papp says.  

 “Now that we have defined a pathway whether TNF or IL-17 antagonism, so let’s see if we can get a compound that works on those pathways,” Dr. Papp said.

In two Phase 3 studies (BE HEARD I and BE HEARD II) evaluating the efficacy and safety of UCB’s bimekizumab in the treatment of adults with moderate to severe hidradenitis suppurativa (HS), patients treated with the investigational interleukin (IL)-17A and IL-17F inhibitor achieved statistically significant and clinically meaningful improvements over placebo in signs and symptoms of hidradenitis suppurativa (HS) at week 16, as measured by Hidradenitis Suppurativa Clinical Response 50 (HiSCR50)

Moreover, bimekizumab demonstrated deep levels of clinical response over placebo at week 16, as measured by HiSCR75, a key secondary endpoint. Clinical responses were maintained with continuous bimekizumab treatment – more than 75% of patients achieved HiSCR50, and more than 55% achieved HiSCR75, at week 48.

The safety profile of bimekizumab across BE HEARD I and BE HEARD II was consistent with previous studies with no new safety signals observed. The most common treatment-emergent adverse events on bimekizumab over 16 weeks were hidradenitis, oral candidiasis, headache, and diarrhea. 

UCB expects to submit global regulatory applications for bimekizumab in moderate to severe HS starting in Q3 2023.  

Novartis’ Cosentyx (secukinumab) is also showing promise in HS. Research has shown that treatment response rates continue to improve beyond the primary Week 16 to more than 55% at Week 52, as evaluated by HiSCR. Safety findings were consistent with what has been seen with Cosentyx in its approved indications

In addition, a Phase 2 study of upadacitinib (UPA) showed that the JAK inhibitor may decrease the inflammatory burden and improve outcomes in patients with HS. 

In a phase 2 study, adults with moderate-to-severe HS were randomized 2:1 to UPA 30 mg (UPA30) once daily or placebo. After 12 weeks, patients on placebo switched to blinded UPA 15 mg through week 48. 

At week 12, higher proportions of patients treated with UPA30 achieved ≥50.0 percent reduction in abscess and inflammatory nodule (AN) count. without an increase in abscess or draining fistula count, and a ≥30 percent reduction and ≥1 unit reduction in Patient’s Global Assessment of Skin Pain compared with historical placebo rates based on adalimumab studies in HS. 

These results support further investigation of UPA for the treatment of moderate-to-severe HS.