TYK2 inhibitor deucravacitinib ‘shows promise’ as novel lupus therapy
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PHILADELPHIA — Phase 2 findings for the tyrosine kinase 2 inhibitor deucravacitinib yielded encouraging results through 48 weeks in patients with systemic lupus erythematosus, according to data presented at ACR Convergence 2022.
“Deucravacitinib has been approved in multiple countries for severe plaque psoriasis,” Marilyn Pike, MD, PhD, of MedPharm Consulting, told attendees.
According to Pike, deucravacitinib (Sotyktu, Bristol Myers Squibb) is an oral, selective, allosteric TYK2 inhibitor. TYK2 mediates signaling of type I interferons (IFNs), interleukin-23 and IL-12, she added.
The 48-week, randomized, double-blind, placebo-controlled, phase 2 trial included 363 patients who met Systemic Lupus International Collaborating Clinics (SLICC) criteria, were seropositive for lupus antibodies and had a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of at least 6. Patients were also required to demonstrate at least one British Isles Lupus Assessment Group (BILAG) index A, or more than two BILAG B, manifestations from the musculoskeletal or mucocutaneous domain.
Eligible participants were being treated with standard background medications, according to Pike. Treatment regimens included deucravacitinib 3 mg twice daily (n = 91), 6 mg twice daily (n = 93) or 12 mg daily (n = 89). The placebo group included 90 patients. Participants additionally underwent mandatory oral corticosteroid tapering between weeks 8 and 20, as well as further tapering between weeks 32 and 40.
“Baseline patient characteristics were very similar to previous lupus trials,” Pike said.
The proportion of patients achieving SLE responder index, based on SRI-4, at week 32 served as the primary outcome measure.
Secondary endpoints at week 48 included SRI-4, BILAG-based Composite Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), decrease of 50% or more from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-50) and change from baseline in active joint count.
According to Pike, 34.4% of patients in the placebo group reached the primary endpoint, compared with 58.2% in the deucravacitinib 3 mg twice daily group (P = .0006), 49.5% in the 6-mg twice daily group (P = .021) and 44.9% in the 12 mg daily group (P = .078).
“I just want to point out that this was a positive trial,” Pike said.
“Importantly, time-to-onset of response was decreased to less than 3 months in the 3-mg BID group,” she added. Meanwhile, the time-to-response was “not much greater than that” in the 6-mg twice daily arm, according to Pike.
For secondary endpoints at 48 weeks, the response rates were 34.4% for placebo, 57.1% for the deucravacitinib 3 mg twice daily group, 47.3% for 6 mg twice daily and 47.2% for 12 mg twice daily.
BICLA results at that time point were 25.6% for placebo, 47.3% for 3 mg twice daily, 35.5% for 6 mg twice daily and 36.0% for 12-mg.
“These were very consistent results,” Pike said.
Further results demonstrated that the 3 mg twice daily deucravacitinib dose was statistically significantly superior to placebo in terms of LLDAS, CLASI-50 and active joint count. The other dosing regimens yielded “clinically meaningful differences” vs. placebo regarding these endpoints, Pike added.
Upper respiratory tract infection, nasopharyngitis, headache and urinary tract infection were the most commonly reported adverse events. There were no fatalities, major cardiac or thrombotic events, systemic opportunistic infections or cases of tuberculosis. Malignancy was “rare,” according to Pike.
“Safety showed that there was no increase in serious adverse events,” she said.
Laboratory data showed that liver and renal function were not affected, according to Pike.
“We feel that deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” Pike said.
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Pike M. Abstract 1117. Presented at: ACR Convergence 2022; Nov. 11-14, 2022; Philadelphia (hybrid meeting).
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