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

Kimball, Alexa B.; Jemec, Gregor B.E.; Alavi, Afsáneh; Réguiai, Z.; Gottlieb, Alice B.; Bechara, Falk G.; Paul, C.; Bourboulis, Evangelos J Giamarellos; Villani, Axel-Patrice; Schwinn, A.; Ruëff, Franziska; Ramaya, Larisha Pillay; Reich, Adam; Lobo, Inês; Sinclair, Rodney; Passeron, Thierry; Martorell, A.; Mendes‐Bastos, Pedro; Kokolakis, Georgios; Becherel, Pierre-André; Wozniak, Magdalena B.; Martinez, Angela Llobet; Wei, Xiaoling; Uhlmann, Lorenz; Passera, Anna; Keefe, Deborah L.; Martin, Ruvie; Field, Clarice; Chen, Li; Vandemeulebroecke, Marc; Ravichandran, Shoba; Muscianisi, Elisa

doi:10.1016/s0140-6736(23)00022-3

Cited by 130 publications

(126 citation statements)

References 37 publications

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“…Recent advances in biologic agents have proven to be highly effective in several immune-mediated diseases, although the benefits in hidradenitis suppurativa are relatively modest with a poor likelihood of complete resolution of symptoms. 7,20 To date, biologic agents appear to be the most effective medical treatment option; adalimumab (TNF inhibitor) has been approved for treating moderate to severe hidradenitis suppurativa, and secukinumab (IL-17A inhibitor) has recently received approval in Europe. 21,22 In phase 3 trials, TNF and IL-17…”

Section: Discussionmentioning

confidence: 99%

“…Although direct comparisons with other clinical studies may not be applicable, the HiSCR response rates for RGRN-305 are in the range with those reported for TNF and IL-17 inhibitors. However, the time to HISCR-50 was faster for biologic agents compared with RGRN-305 . Nevertheless, RGRN-305 offers advantages inherent to the nature of small-molecule therapeutics, such as oral administration, lower manufacturing cost, and no immunogenicity risk.…”

Section: Discussionmentioning

confidence: 99%

“…Abscesses, mean (SD) 1.1 (0.9) 0.4 (0.5) 0.9 (0. inhibition has been demonstrated to be viable treatment strategies, 6,20,23 whereas IL-23 or IL-36 inhibition had no significant effect in phase 2 trials. [24][25][26][27] Given the fluctuating disease activity in hidradenitis suppurativa, high placebo response rates may be observed using HiSCR-50, which emphasizes the importance of incremental benefit compared with placebo or the use of more-stringent end points, such as HiSCR-75 and HiSCR-90.…”

Section: Lesion Countsmentioning

confidence: 99%

“…However, the time to HISCR-50 was faster for biologic agents compared with RGRN-305. 6,7,20 Nevertheless, RGRN-305 offers advantages inherent to the nature of small-molecule therapeutics, such as oral administration, lower manufacturing cost, and no immunogenicity risk. Moreover, in this trial, RGRN-305 demonstrated good safety and tolerability without changes in blood biochemistry tests.…”

Section: Lesion Countsmentioning

confidence: 99%

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Efficacy and Safety of the Heat Shock Protein 90 Inhibitor RGRN-305 in Hidradenitis Suppurativa

Ben Abdallah,

Bregnhøj,

Emmanuel

et al. 2024

JAMA Dermatol

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ImportanceHidradenitis suppurativa is a painful immune-mediated disorder with limited treatment options; hence, a need exists for new treatments.ObjectiveTo evaluate the feasibility of heat shock protein 90 inhibition by RGRN-305 as a novel mechanism of action in treating moderate to severe hidradenitis suppurativa.Design, Setting, and ParticipantsThis was a parallel-design, double-blind, proof-of-concept, placebo-controlled randomized clinical trial conducted between September 22, 2021, and August 29, 2022, at the Department of Dermatology, Aarhus University Hospital in Denmark. The study included a 1- to 30-day screening period, a 16-week treatment period, and a 4-week follow-up period. Eligibility criteria included age 18 years or older and moderate to severe hidradenitis suppurativa with 6 or more inflammatory nodules or abscesses in at least 2 distinct anatomic regions. Of 19 patients screened, 15 patients were enrolled in the study. Intention-to-treat analysis was performed.InterventionsPatients were randomly assigned (2:1) to receive oral RGRN-305, 250-mg tablet, or matching placebo once daily for 16 weeks.Main Outcomes and MeasuresThe primary efficacy end point was the percentage of patients achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR-50) at week 16. Secondary efficacy end points included HiSCR-75 or HiSCR-90, Hidradenitis Suppurativa Physician’s Global Assessment, Dermatology Life Quality Index scores, and a pain numeric rating scale. Safety was assessed by adverse events, physical examinations, clinical laboratory measurements, and electrocardiograms.ResultsA total of 15 patients were enrolled, completed the study, and were included in all analyses (10 [67%] female; median age, 29 [IQR, 23-41] years). The primary end point HiSCR-50 at week 16 was achieved by a higher percentage in the RGRN-305 group (60% [6 of 10]) than in the placebo group (20% [1 of 5]). Improvements were also observed across all secondary end points at week 16, including higher rates of the harder-to-reach HiSCR levels; 50% (5 of 10) achieved HiSCR-75 and 30% (3 of 10) achieved HiSCR-90, whereas none of the placebo-treated patients achieved HiSCR-75 or HiSCR-90. RGRN-305 was well tolerated, with no deaths or serious adverse events, and treatment-emergent adverse events were similarly frequent between the RGRN-305 and placebo groups.Conclusions and RelevanceThe findings of this trial suggest that heat shock protein 90 inhibition by RGRN-305 offers a novel mechanism of action in treating hidradenitis suppurativa, warranting further evaluation in larger trials.Trial RegistrationClinicalTrials.gov Identifier: NCT05286567

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Lesion Countsmentioning

confidence: 99%

Section: Lesion Countsmentioning

confidence: 99%

See 2 more Smart Citations

Efficacy and Safety of the Heat Shock Protein 90 Inhibitor RGRN-305 in Hidradenitis Suppurativa

Ben Abdallah,

Bregnhøj,

Emmanuel

et al. 2024

JAMA Dermatol

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“…These findings offer valuable insights into the role of serine and onecarbon metabolism in NMSC and have the potential to identify promising targets for therapeutic intervention. 3 This study compared two phase III randomized trials, SUNSHINE and SUNRISE, which evaluated the efficacy of the monoclonal antibody secukinumab. Enrolled patients had moderate to severe hidradenitis suppurativa, and clinical response was measured as a 50% decrease in abscesses and inflammatory nodules without increase in abscesses or fistulas.…”

Section: Stephanie M Bollard Mbbch Mater Misericordiae University Hos...mentioning

confidence: 99%

Spotlight in Plastic Surgery: October 2023

Phillips,

Bollard,

Chang

et al. 2023

Plastic &Amp; Reconstructive Surgery

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Extracellular Vesicles Derived from Ligament Tissue Transport Interleukin‐17A to Mediate Ligament‐To‐Bone Crosstalk in Ankylosing Spondylitis

Wang,

Lu,

Song

et al. 2024

Advanced Science

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Pathological new bone formation is a critical feature of the progression of ankylosing spondylitis (AS), and spine ankylosis is a distinctive feature of this condition. Ligaments are the primary regions of pathological new bone formation in AS. Here, it is demonstrated that ligament tissue‐derived extracellular vesicles (EVs) and their interleukin‐17A (IL‐17A) cargo mediate the communication between the tissue and other cells. The investigation revealed that IL‐17A in EVs can activate the JAK‐STAT3 pathway, thereby stimulating the expression of MMP14 in AS ligament. Overexpression of MMP14 can lead to changes in the cytoskeleton and mechanical signaling of mesenchymal stem cells and other cells. These alterations in cellular cytoskeleton and mechanical signaling at ligament sites in patients with AS or in stem cells treated with EVs can result in pathological new bone formation. Finally, inhibiting IL‐17A activity and EV endocytosis effectively controlled inflammation and pathological new bone formation. Overall, these data suggest that ligament‐derived EVs and the enclosed IL‐17A have a potential role in driving pathological new bone formation in AS, and targeting EVs may therefore emerge as a novel approach to delaying ectopic ossification in AS.

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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

Cited by 130 publications

References 37 publications

Efficacy and Safety of the Heat Shock Protein 90 Inhibitor RGRN-305 in Hidradenitis Suppurativa

Efficacy and Safety of the Heat Shock Protein 90 Inhibitor RGRN-305 in Hidradenitis Suppurativa

Spotlight in Plastic Surgery: October 2023

Extracellular Vesicles Derived from Ligament Tissue Transport Interleukin‐17A to Mediate Ligament‐To‐Bone Crosstalk in Ankylosing Spondylitis

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