DENVER – Two therapeutic candidates for severe hidradenitis suppurativa (HS) achieved major responses that proved durable in the randomized trials reported here.
The IL-17A/F inhibitor sonelocimab achieved at least 75% skin clearance (HiSCR 75) at 40 weeks in 62% of patients enrolled in similar phase III clinical trials. Two different doses of the oral JAK1 inhibitor povorcitinib produced at least 50% clearance (HiSCR 50) in 57–71% of patients after 54 weeks of follow-up in two separate trials.
Both agents were well tolerated and were associated with low rates of serious and grade ≥3 treatment-emergent adverse events (TEAEs), as reported at the American Academy of Dermatology meeting.
“(Sonelocimab) had a very rapid onset of clinical improvement that continued through week 40, with a really meaningful increase in improvement in both clinical metrics and quality of life measures,” said Alexa Kimball, MD, MPH, of Beth Israel Deaconess Medical Center in Boston. “Having mild or no effect of HS on most of these patients at 40 weeks, I think is really quite significant, especially given that this is an evaluation designed specifically for HS patients…. Dosing every 1 month is, of course, convenient for patients.”
Follow-up will continue until week 52.
In the STOP-HS1 and HS2 trials, povorcitinib produced deep responses in a large proportion of patients, which were associated with significant improvements in quality of life.
“Povorcitinib demonstrated substantial clinical efficacy through week 54, as 29% of patients achieved a high score (HiSCR) of 100,” said Martina Porter, MD, of Beth Israel Deaconess Medical Center. “We saw really good responses to inflammatory nodules, abscesses, and drainage tunnels (ANDT), and it really led to meaningful improvements in skin pain, fatigue, and quality of life. In terms of complete inflammation clearance, we also saw an ANDT count of 0 – no abscesses, inflammatory nodules, or drainage tunnels at 54 weeks – and up to 20% of patients achieved the endpoint.”
“Both doses of povorcitinib were generally very well tolerated over the course of 54 weeks of treatment,” he said. “This really supports the potential of povorcitinib to treat moderate to severe HS in the future.”
Vela trial of sonelocimab
Sonelocimab is a member of a novel biologic class known as a nano body. In contrast to a conventional monoclonal antibody, a nanobody is a smaller antigen-binding fragment, with increased binding sensitivity, lower toxicity, and better overall safety.
“This allows us to do some interesting things, like combining two different parts together (IL-17A and F), combined with an anti-albumin component, allowing higher persistence in the bloodstream and other locations,” Kimball said. “We think that smaller features may have some advantages in terms of pharmacodynamics and drug penetration.”
Sonelocimab treatment shows positive results in Phase 2 trials psoriatic arthritis And rash psoriasis, Also H.S.. Kimball reported findings after 40 weeks of follow-up in phase III Vela-1 And Vela-2. The trials included a total of 838 adult patients with moderate/severe HS who were randomized 2:1 to sonelocimab or placebo. The primary endpoint was HiSCR 75 response rate at 16 weeks. A previous report showed that one-third of patients treated with IL-17 inhibitors met the primary endpoint, compared to 18-25% of placebo-treated patients.
Updated analysis after 40 weeks showed that 62% of patients in both trials achieved HiSCR 75 responses, and 74–79% of patients achieved HiSCR 50 responses. Additionally, 36–40% of patients treated with sonelocimab had HiSCR 90 responses, and approximately 30% had complete clearance (HiSCR 100) in both trials combined. The novel therapy produced substantial improvements in the most common types of HS lesions, including a 71–75% reduction in inflammatory nodules, 72–79% for abscesses, and 60–69% for drainage tunnels.
Clinical improvement was associated with substantial improvement in quality of life, as more than 60% of patients treated with sonelocimab reported “mild/none” for their severity rating at week 40.
Analysis of 52-week safety data is ongoing, but 16-week data showed that serious TEAEs occurred in 2.5% of patients treated with the IL-17 inhibitor. The most common TEAEs associated with sonelocimab were nasopharyngitis (8.6%) and oral candidiasis (7.3%).
In addition to continued follow-up in the VELA trials, ongoing studies are evaluating the IL-17 nanobody in a long-term extension of the VELA program, and a separate trial is evaluating the novel agent in adolescents, Kimball said.
Stop-HS1&2
In his introduction to the povorcitinib data, Porter reiterated a common answer to the question of how JAK inhibitors interfere with HS: “I don’t think we really know that answer, but looking at this data, you can see that[the disease]has a deep response to JAK inhibition.”
The STOP-HS1 and HS2 trials involved more than 1,200 adults with moderate/severe HS who were randomly assigned to receive one of two doses of povorcitinib or placebo. The primary endpoint was HiSCR 50 response rate at 12 weeks. As reported last yearThe primary analysis showed hiSCR50 responses in 40–42% of patients treated with any dose of a JAK inhibitor in two trials.
The updated analysis after week 54 showed deeper responses, as the HiSCR50 rate increased by approximately 50% from weeks 12 to 54 with povorcitinib for both doses of the JAK inhibitor in both trials. Patients who received povorcitinib after 12 weeks had strong responses that deepened over time, including high-threshold responses of HiSCR 75, 90, and 100.
One to two-thirds of patients treated with povorcitinib had clinically meaningful improvements in multiple measures of quality of life, Porter said.
Severe TEAEs occurred in 4–6% of povorcitinib-treated patients and grade ≥3 TEAEs occurred in 5–8%. The most common TEAEs associated with JAK inhibitors were acne, nasopharyngitis, and upper respiratory tract infection. Of the AEs of special interest, only one major adverse cardiovascular event occurred, eight thromboembolic events occurred, and no fatalities occurred in approximately 1,200 patients treated with the drug, including those who crossed over to placebo. Serious and opportunistic infections occurred in 0-2% of patients treated with any dose in both trials.
