Secukinumab’s Serum Pharmacokinetics, Safety Results Highlighted in Patients with HS

Serum pharmacokinetic (PK) and drug concentration levels of secukinumab in individuals with hidradenitis suppurativa (HS) are impacted by HS severity, body weight, and baseline high-sensitivity C-reactive protein (hsCRP) levels, new findings suggest.1

These data resulted from a new exploratory analysis of the pooled phase 3 SUNSHINE and SUNRISE trial program findings.2 The investigators assessed serum PK as well as safety findings of secukinumab 300 mg given every 2 weeks (SECQ2W) or every 4 weeks (SECQ4W). Afsaneh Alavi, MD—from the Mayo Clinic’s Department of Dermatology in Rochester, Minnesota—led a group of investigators in the authoring of this study.

“Herein, we present pooled data from SUNSHINE and SUNRISE to evaluate secukinumab's PK, and the impact of baseline weight, disease severity, and inflammatory burden on PK levels, the resulting exposure–response relationships including efficacy, the effect of treatment on hsCRP levels as well as the safety profile of secukinumab in patients with moderate-to-severe HS over 52 weeks,” Alavi et al wrote.1

Study Design Details

Alavi and colleagues highlighted the SUNSHINE and SUNRISE trial designs, noting that these were parallel, multi-center, randomized, placebo-controlled, double-blind phase 3 studies which were conducted to assess both the short-term (through 16 weeks) and long-term (through 52 weeks) efficacy and safety of secukinumab among adult patients with moderate-to-severe HS.

Those deemed eligible by both studies' investigators as participants had been adults ≥18 years with a diagnosis of moderate-to-severe HS. The latter criteria had been defined as presenting at least 5 inflammatory lesions across a minimum of 2 distinct anatomical areas. Those taking part in SUNSHINE and SUNRISE were randomized in a 1:1:1 ratio to be treated subcutaneously in the SECQ2W group or the SECQ4W group.

Otherwise, subjects would be given a placebo from baseline through the 16-week mark. After this point, those who had originally been assigned to secukinumab continued on their respective dosing schedule. Meanwhile, participants who had been given a placebo were re-randomized to either SECQ2W (placebo-SECQ2W) or SECQ4W (placebo-SECQ4W) through the 52-week mark.

Alavi and coauthors' pooled exploratory analysis from of these phase 3 trials looked at the safety and PK of secukinumab at the 2 aforementioned dosing regimens. A population PK model was implemented by the investigative team to assess the impact of of body weight, severity of disease, and baseline hsCRP on subjects' serum drug levels.

Alavi et al's exposure–response analysis explored the link between predicted PK values and clinical outcomes, with results being determined via the Hidradenitis Suppurativa Clinical Response (HiSCR). No formal confirmatory statistical testing was conducted by the team.

Findings on PK and Safety of Secukinumab

By the 16, 24, and 52-week marks, the average trough serum concentration of secukinumab was shown to be approximately 2 times higher in the SECQ2W cohort compared to those in the SECQ4W cohort.1 By 16-week mark, the degree of exposure overlap between the 2 dosing arms was significant, with a numerical—but not statistically tested—improvement in HiSCR of roughly 3% greater with SECQ2W versus SECQ4W. By the 52-week mark, rates of HiSCR had reached a plateau.

Shifts in participants' hsCRP levels were also observed by Alavi and coauthors. From baseline to Week 16, hsCRP dipped from 18.6 ± 26.3 mg/L to 12.8 ± 18.0 mg/L with SECQ2W, and from 15.9 ± 27.6 mg/L to 11.5 ± 18.4 mg/L with SECQ4W, while the placebo arm demonstrated a lack of notable reductions (14.4 ± 22.5 mg/L to 14.7 ± 23.8 mg/L). The observed reductions were sustained through the 52-week mark.

Additionally, the investigative team concluded that increased body weight, greater HS severity, and elevated baseline hsCRP all show a link with lower circulating concentrations of secukinumab. The team added that the incidence of anti-drug antibodies was low (<1%), highlighting that no new safety concerns had emerged during the analysis. Importantly, there was no dose–response relationship, and Alavi and colleagues found that secukinumab's overall safety profile remained consistent with that observed in other approved indications.

Taken together, such findings would indicate that serum secukinumab exposure in HS varies according to these patient characteristics. It would also suggest that SECQ2W dosing may provide added benefit in certain types of patients.

“Treatment with secukinumab, whether administered Q2W or Q4W, led to a reduction in baseline hsCRP levels through Week 52,” they concluded.1 “Secukinumab treatment showed a low incidence of immunogenicity, with no new or dose-related safety signals identified in patients with HS.”

References

1. A Alavi, Z Reguiai, GBE Jemec, et al. “ Secukinumab in the Treatment of Moderate-to-Severe Hidradenitis Suppurativa: Pooled Pharmacokinetics and Safety Results From the SUNSHINE and SUNRISE Phase 3 Studies,” International Journal of Dermatology (2025): 1–10, https://doi.org/10.1111/ijd.70025.

2. AB Kimball, GB Jemec, A Alavi, et al. “Secukinumab in Moderate-To-Severe Hidradenitis Suppurativa (SUNSHINE and SUNRISE): Week 16 and Week 52 Results of Two Identical, Multicentre, Randomised, Placebo-Controlled, Double-Blind Phase 3 Trials,” Lancet 401 (2023): 747–761.