Povorcitinib Met Phase 3 Endpoints in Hidradenitis Suppurativa

Key Takeaways

• Across 1,227 adults with moderate-to-severe hidradenitis suppurativa in STOP-HS1 and STOP-HS2, both once-daily povorcitinib doses met the week-12 HiSCR50 primary endpoint.
• In STOP-HS1, HiSCR50 responses were 40% with povorcitinib 45 mg and 41% with povorcitinib 75 mg versus 30% with placebo.
• In STOP-HS2, HiSCR50 responses were 42% with both povorcitinib doses versus 29% with placebo.
• Serious treatment-emergent adverse events through week 12 occurred in 1% to 2% of patients receiving povorcitinib and 2% to 3% of those receiving placebo.
• Through week 54, serious adverse events occurred in 5% of patients receiving povorcitinib 45 mg and 6% of those receiving povorcitinib 75 mg.

Moderate-to-severe hidradenitis suppurativa continues to have limited systemic treatment options, keeping oral targeted therapy a clinically important question as late-stage data emerge. Povorcitinib, an oral Janus kinase 1 inhibitor, moved into paired phase 3 testing in adults with disease severe enough to warrant systemic treatment, setting up a direct comparison with placebo before planned crossover.

Martina L. Porter, MD, and colleagues reported the randomized, double-blind, placebo-controlled STOP-HS1 and STOP-HS2 phase 3 trial in Nature Medicine, published online July 23, in adults with moderate-to-severe hidradenitis suppurativa (HS). STOP-HS1 enrolled 608 patients and STOP-HS2 enrolled 619 patients; adults were assigned in a 2:2:1:1 ratio to once-daily povorcitinib 45 mg, povorcitinib 75 mg, placebo with crossover to povorcitinib 45 mg at week 12, or placebo with crossover to povorcitinib 75 mg at week 12, with treatment continuing through week 54. The primary endpoint was Hidradenitis Suppurativa Clinical Response 50 (HiSCR50), defined as at least a 50% decrease in total abscess and inflammatory nodule count with no increase from baseline in abscess or draining tunnel count.

Both povorcitinib doses met the primary endpoint in both studies. In STOP-HS1, week-12 HiSCR50 responses were 40% with povorcitinib 45 mg and 41% with povorcitinib 75 mg versus 30% with placebo, with reported odds ratios of 1.6 and 1.6. In STOP-HS2, the corresponding response rates were 42% and 42% versus 29%, with reported odds ratios of 1.8 and 1.9.

Serious treatment-emergent adverse events through week 12 occurred in 1% to 2% of patients across povorcitinib doses and in 2% to 3% across placebo. Through week 54, serious adverse events were reported in 5% of patients receiving povorcitinib 45 mg and 6% of those receiving povorcitinib 75 mg.

The investigators said these paired phase 3 findings support the potential of oral povorcitinib as a treatment option for adults with moderate-to-severe HS.

Clinician Questions

Which patients with hidradenitis suppurativa were represented in STOP-HS1 and STOP-HS2?

STOP-HS1 and STOP-HS2 enrolled adults with moderate-to-severe hidradenitis suppurativa, so the reported findings apply to adults with more burdensome disease and are not extended here to pediatric populations or to milder presentations.

How should the week 54 safety figures for povorcitinib in hidradenitis suppurativa be interpreted after placebo crossover?

Because placebo groups crossed over to active treatment at week 12 and treatment continued through week 54, the longer-term serious adverse-event findings reflect active-treatment experience rather than a continuing placebo-controlled comparison.