brepocitinib (PF-06700841) / Pfizer, Priovant Therap - LARVOL DELTA

Program-Specific Highlights and Updates (GlobeNewswire) - "Preparation for commercial launch of brepocitinib in DM is underway; NDA filing expected in early calendar year 2026 with potential commercial launch early in calendar year 2027; Phase 3 trial for brepocitinib in NIU is fully enrolled ahead of schedule with topline data expected in the second half of calendar year 2026, previously expected in the first half of calendar year 2027; Proof-of-concept trial for brepocitinib in CS is fully enrolled ahead of schedule with topline data expected in the first half of calendar year 2026, previously expected in the second half of calendar year 2026."

Clinical data • FDA filing • Launch US • Dermatomyositis • Sarcoidosis • Uveitis

P114 Efficacy and safety of oral Janus kinase, tyrosine kinase 2 and phosphodiesterase 4 inhibitors in the treatment of chronic plaque psoriasis: a network meta-analysis. (PubMed, Br J Dermatol) - "After 16-24 weeks of treatment, tofacitinib and deucravacitinib had the highest efficacy, followed by apremilast, orismilast, upadacitinib and brepocitinib. Zasocitinib, a new highly selective allosteric TYK2 inhibitor, has recently demonstrated promising efficacy in the treatment of psoriasis, with 33% of patients achieving PASI 100 (complete clearance of psoriasis lesions) after just 12 weeks of treatment. In conclusion, oral TYK2 inhibitors have shown efficacy in the treatment of chronic plaque psoriasis comparable with adalimumab, with newer agents demonstrating enhanced effectiveness and surpassing PDE-4 inhibitors in therapeutic outcomes. JAK inhibitors, particularly tofacitinib, exhibit comparable efficacy to some TYK2 and PDE-4 inhibitors."

Clinical • Journal • Retrospective data • Review • Dermatology • Immunology • Psoriasis • TYK2

Efficacy and Safety of Brepocitinib in Patients with Active Dermatomyositis: Results from a Randomized, Double-Blind, Multicenter, Placebo-Controlled, Phase III (VALOR) Trial (ISDS 2025) - P3 | "For participants receiving oral corticosteroids (OCS) at baseline, there was a mandatory taper between weeks 12 and 36 to prednisone ≤ 5 mg QD. VALOR is the first positive, randomized, double-blind, placebo-controlled study of a targeted oral therapeutic in DM, distinguished by its 52-week duration and largest enrolled clinical trial population to date. BREPO 30 mg QD achieved statistically significant and clinically meaningful efficacy, with rapid, consistent, and sustained benefits across skin, muscle, and QOL outcome measures. Safety was consistent with prior BREPO studies and supports a favorable benefit-risk profile."

Clinical • P3 data • Dermatology • Dermatomyositis • Immunology • Myositis • JAK1 • TYK2

Major Upcoming Milestones (GlobeNewswire) - "Priovant plans to file an NDA for brepocitinib in DM in the first half of calendar year 2026. Topline data from the ongoing Phase 3 trial of brepocitinib in NIU and proof-of-concept trial in CS are expected in the first half of calendar year 2027 and second half of calendar year 2026, respectively."

Clinical data • FDA filing • Dermatomyositis • Sarcoidosis • Uveitis

Brepocitinib Inhibits Key Pathogenic Cytokine Signaling in Dermatomyositis Patients (ACR Convergence 2025) - P3 | "Previous data has suggested that brepocitinib 30 mg may demonstrate superior inhibition of DM-relevant cytokine signaling in vitro compared to tofacitinib, a JAK1/JAK3 inhibitor.1 The purpose of this study was to evaluate the ability of brepocitinib to inhibit pathogenic cytokine signaling ex vivo in peripheral blood mononuclear cells (PBMCs) from patients with DM and healthy donors. PBMCs were isolated from whole blood from six participants with a diagnosis of DM according to the 2017 EULAR/ACR Classification Criteria for Idiopathic Inflammatory Myopathies and screened for baseline responsiveness to cytokine stimulation. Brepocitinib demonstrated potent inhibition of proinflammatory cytokine signaling in PBMCs at exposures achieved with brepocitinib 30 mg QD. This inhibition was more potent in samples from patients with DM than healthy donors, which may reflect pathologic overactivation of JAK-STAT signaling in DM. These results confirm findings from previous work..."

Clinical • Dermatology • Dermatomyositis • Immunology • Myositis • IFNA1 • IFNB1 • IL6 • JAK1 • JAK3 • STAT1 • TYK2

Efficacy and safety of oral JAK, TYK2 and PDE4 inhibitors in the treatment of chronic plaque psoriasis - a network meta-analysis (EADV 2025) - "After 12-16 weeks of treatment, solcitinib (PASI75 odds ratio [OR] 37.92) had the highest efficacy compared to placebo , followed by zasocitinib (34.59), tofacitinib (22.01), ropsacitinib (16.79), brepocitinib (14.88) and deucravacitinib (14.17). Oral TYK2 inhibitors have shown efficacy in the treatment of chronic plaque psoriasis comparable to adalimumab, with newer agents demonstrating enhanced effectiveness and far surpassing PDE4 inhibitors in therapeutic outcomes. JAK inhibitors, particularly solcitinib and tofacitinib, exhibit comparable efficacy to TYK2 inhibitors. EADV Congress 2025 PARIS"

Retrospective data • Dermatology • Immunology • Psoriasis • TYK2

Rapid Improvement of Cutaneous Dermatomyositis with Brepocitinib: A 12-Week Open-Label Trial (EADV 2025) - P2 | "In a population with recalcitrant, severe cutaneous DM, brepocitinib was associated with rapid, clinically meaningful improvement in CDASI-A in all participants during 12 weeks of treatment. Consistent benefits were observed in other clinician- and patient-reported measures of skin activity. The results of a global phase III, randomized, placebo-controlled, dose-ranging, 52-week trial of brepocitinib in adult DM patients with skin and muscle disease (VALOR, NCT0543726) are forthcoming and will further clarify the potential of brepocitinib for the treatment of DM."

Clinical • Dermatology • Dermatomyositis • Immunology • Infectious Disease • Myositis • IL12A • IL23A • IL6 • JAK1 • TYK2

Roivant and Priovant Announce Positive Phase 3 VALOR Study Results for Brepocitinib in 52-Week Placebo-Controlled Trial in Dermatomyositis (DM) (Roivant Sciences) - "On the primary endpoint, brepocitinib 30 mg achieved a week 52 mean Total Improvement Score (TIS) of 46.5 compared to 31.2 for placebo (p=0.0006​), even with nearly twice as many patients coming off background steroids on brepocitinib 30 mg compared to placebo....Safety profile was consistent with previous clinical trials of brepocitinib and NDA filing is planned for calendar 1H 2026."

FDA filing • P3 data • Dermatomyositis

Unravelling the transcriptomic landscape of primary lymphocytic scarring alopecias: systematic review and meta-analysis. (PubMed, Front Immunol) - "Drug repurposing analyses identified candidate compounds modulating inflammation and metabolism, some reversing inflammatory signatures in brepocitinib-treated samples. This integrated molecular analysis refines our understanding of PLSA subtypes and proposes candidate biomarkers and therapeutic targets, supporting a shift toward biomarker-driven classification and personalized treatment strategies. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024559969."

Clinical • Journal • Retrospective data • Review • Alopecia • Cardiovascular • Fibrosis • Immunology • Inflammation • Lichen Planus • Metabolic Disorders • IFNG

Recent Developments (GlobeNewswire) - "Phase 3 VALOR study for brepocitinib evaluating its use in patients with DM...last patient last visit completed in July."

Enrollment closed • Dermatomyositis

Major Upcoming Milestones (GlobeNewswire) - "Priovant plans to report topline data from the ongoing Phase 3 trial of brepocitinib in DM in the second half of calendar year 2025 and topline data from the ongoing Phase 3 trial of brepocitinib in NIU in the first half of calendar year 2027. Topline results for the Phase 2 trial in CS are expected in the second half of calendar year 2026."

P2 data • P3 data: top line • Dermatomyositis • Sarcoidosis • Uveitis

Roivant and Priovant to Host Investor Video Conference at 1:00 PM ET on Tuesday, June 17 on Brepocitinib and the Unmet Medical Need in Dermatomyositis (Roivant Sciences) - "Roivant...and Priovant Therapeutics today announced that they will host a live investor video conference at 1:00 PM ET on Tuesday, June 17 on brepocitinib, the unmet medical need for patients with dermatomyositis (DM) and the potential role brepocitinib could play in improving the lives of patients with DM."

Clinical • Dermatomyositis

Brepocitinib Phase 2 trial doses first cutaneous sarcoidosis patients (Sarcoidosis News) - "The first participants in a Phase 2 clinical trial testing brepocitinib, Roivant’s experimental oral treatment, in adults with cutaneous sarcoidosis have been dosed, and top-line results are expected in the second half of 2026...The company had this year announced plans to launch this proof-of-concept trial, called BEACON (NCT06978725), which is recruiting up to 28 adult patients across four locations across the U.S. The study is designed to evaluate the safety and efficacy of two doses of brepocitinib against a placebo."

P2 data • Trial status • Sarcoidosis

Major Upcoming Milestones (GlobeNewswire) - "Priovant plans to report topline data from the ongoing Phase 3 trial of brepocitinib in DM in the second half of...2025 and topline data from the ongoing Phase 3 trial of brepocitinib in NIU in the first half of...2027. Topline results for the Phase 2 trial in CS are expected in the second half of...2026. Roivant and Priovant will be hosting an upcoming investor event on brepocitinib at 1:00 p.m. ET on Tuesday, June 17, 2025; Immunovant expects to report batoclimab six-month remission data from the proof-of-concept study in GD in the summer of 2025 and Phase 3 thyroid eye disease (TED) data in the second half of calendar year 2025. Immunovant plans to initiate a potentially registrational trial evaluating IMVT-1402 in SjD and a second potentially registrational trial in GD in the summer of 2025; Pulmovant plans to report topline data from the ongoing Phase 2 trial of mosliciguat in pulmonary hypertension associated with interstitial lung disease in the second half of...2026"

Clinical data • New trial • Dermatomyositis • Grave’s Disease • Hypertension • Immunology • Sjogren's Syndrome • Thyroid Eye Disease • Uveitis

Brepocitinib improves inflammation and fibrosis in cicatricial alopecias through transcriptomic changes (SID 2025) - P2 | "Brepocitinib was well tolerated and consistent with safety reported in other clinical studies. Taken together, brepocitinib significantly reduced markers of inflammation and fibrosis in the lesional scalp of FFA/ LPP and CCCA patients, supporting its potential as a therapeutic option in CA patients."

IO biomarker • Late-breaking abstract • Alopecia • Fibrosis • Immunology • Inflammation • Lichen Planus • CCL2 • CCR2 • COL12A1 • COL5A3 • COL8A2 • CXCL9 • CXCR3 • IL10 • IL2RA • IL32 • IL6R • IL7R • IRF1 • MX1 • OASL • STAT1 • TYK2

Proteomic analysis of serum from brepocitinib-treated cicatricial alopecia patients reveals downregulation of key biomarkers of inflammation and fibrosis (SID 2025) - P2 | "Brepocitinib was well tolerated and consistent with safety reported in prior studies. Overall, the reduction of inflammatory and fibrotic serum biomarker expression paralleled clinical improvement in brepocitinib-treated CA patients, further supporting its role in targeting key drivers of CA disease pathogenesis."

Biomarker • Clinical • Late-breaking abstract • Omic analysis • Alopecia • Cardiovascular • Fibrosis • Immunology • Inflammation • Lichen Planus • CCL19 • CD8 • COL1A1 • CTSD • CXCL1 • CXCL10 • CXCL11 • CXCL8 • CXCL9 • IL2RA • SPP1 • TNFRSF9 • TYK2

Effects of JAK/STAT inhibitors in cutaneous T-cell lymphoma cells (SID 2025) - "Four JAK inhibitors were tested: Abrocitinib (JAK1), Tofacitinib (pan-JAK, potent JAK3 inhibition), Ritlecitinib (JAK3), and Brepocitinib (pan-JAK, potent TYK2/JAK1 inhibition). Notably, Tofacitinib combined with AS1517499 or TTI-101 showed synergistic apoptotic effects, as did the combination of the two STAT inhibitors. These findings underscore the efficacy of JAK/ STAT inhibitors in MJ and HuT 78 cells, highlight differential sensitivities between the cell lines, and support ongoing investigations into the underlying mechanisms."

Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • JAK1 • JAK3 • STAT3 • STAT6 • TYK2

A 12-Week Open-Label Study to Investigate the Efficacy and Safety of Brepocitinib in Adults With Skin-Predominant Dermatomyositis (clinicaltrials.gov) - P2 | N=5 | Completed | Sponsor: Priovant Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Dermatomyositis • Immunology • Myositis

SYMPTOM RESPONSE TRAJECTORY ANALYSIS IDENTIFIES DISTINCT SUBPOPULATIONS IN MODERATE-TO-SEVERE ULCERATIVE COLITIS LINKED TO MAINTENANCE OUTCOMES: A PATIENT LEVEL POST-HOC ANALYSIS OF 2,378 PARTICIPANTS ACROSS 6 RCT'S WITH 8 ADVANCED THERAPIES (DDW 2025) - "Posthoc analysis of the SELECTION trial (filgotinib) demonstrated that analysis of daily PRO2 scores (stool frequency/rectal bleeding) as time-series data reveals discrete subpopulations...Methods In a cross-industry/academia collaboration, data from 2,378 UC participants from RCTs of adalimumab, brepocitinib, etrasimod, etrolizumab, ozanimod, ritlecitinib, ustekinumab, and vedolizumab in UC were analyzed for PRO2-based treatment symptom response trajectories using group-based trajectory modeling (GBTM)...Symptom response trajectories may reflect underlying heterogeneity in individual disease biology in interaction with different MOA (i.e. endotypes). RNASeq analysis of transcriptome regulation in these patients aims to further explore this hypothesis."

Clinical • Metastases • Retrospective data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Phase 2 Study of the Safety and Efficacy of Brepocitinib in Adults With Cutaneous Sarcoidosis (BEACON) (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: Priovant Therapeutics, Inc.

New P2 trial • Immunology • Sarcoidosis

The Relative Efficacy and Safety of Monotherapies for Alopecia Areata: A Network Meta-Analysis Study. (PubMed, J Cosmet Dermatol) - "We produced high-quality evidence on the comparative effectiveness of monotherapies for AA with various regimens of 8 JAKIs, including the FDA-approved ones. Our findings can improve clinicians' decision-making and update guidelines for medical practice."

Clinical • Journal • Retrospective data • Review • Alopecia • Immunology

Clinical response trajectories identify distinct subpopulations of ulcerative colitis patients and are linked to disease outcome across different therapy classes. Patient level analysis of 2378 participants from 6 randomized controlled trials in moderate-severe UC representing 8 different mechanisms of action. (ECCO-IBD 2025) - "Post hoc analysis of the SELECTION trial (filgotinib) demonstrated that treating daily PRO2 scores (stool frequency, rectal bleeding) as time-series data reveals discrete subpopulations.Patients with in the faster response trajectory groups achieve wk52 endpoints at higher rates including disease control. Methods In a cross-industry/academic collaboration, data from 2,378 UC responders from RCTs of adalimumab, brepocitinib, etrasimod, etrolizumab, ozanimod, ritlecitinib, ustekinumab, and vedolizumab in UC were analyzed for PRO2-based treatment response trajectories using Group-based trajectory modeling (GBTM)...Response trajectories likely reflect underlying heterogeneity in disease biology in the interaction with the different MOA (i.e. endotypes). RNASeq analysis of transcriptome regulation in these patients aims to further explore this hypothesis."

Clinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Roivant Reports Financial Results for the Third Quarter Ended December 31, 2024, and Provides Business Update (GlobeNewswire) - "Priovant plans to report topline data from the ongoing Phase 3 trial of brepocitinib in DM in the second half of calendar year 2025 and topline data from the ongoing Phase 3 trial of brepocitinib in NIU in the first half of calendar year 2027. Priovant’s Phase 2 trial of brepocitinib in cutaneous sarcoidosis is expected to begin in the second quarter of calendar year 2025; topline results are expected in the second half of calendar year 2026. Pulmovant plans to report topline data from the ongoing Phase 2 trial of mosliciguat in pulmonary hypertension associated with interstitial lung disease in the second half of calendar year 2026. Genevant litigation against Moderna continues to progress with summary judgment phase scheduled for second and third quarter of calendar year 2025; Moderna jury trial scheduled for September 2025."

New P2 trial • New trial • P2 data • P3 data • Dermatomyositis • Hypertension • Rare Diseases • Sarcoidosis • Uveitis

Brepocitinib, a Selective TYK2/JAK1 Inhibitor Under Evaluation for the Treatment of Dermatomyositis, Reduces Inflammatory Cytokine Signaling and Interferon-induced Apoptosis in Primary Human Epidermal Keratinocytes (ACR Convergence 2024) - P3 | "Cutaneous disease activity in DM is marked by pro-inflammatory cytokine upregulation via the JAK-STAT pathway and aberrant keratinocyte apoptosis. Brepocitinib significantly reduced STAT1 and STAT3 phosphorylation in IFN-stimulated HEKa. In addition, brepocitinib led to concentration-dependent reductions in pro-inflammatory gene expression levels, including IL-6, and normalized apoptosis to basal levels in IFN-stimulated HEKa."

Dermatomyositis • Immunology • Myositis • ANXA5 • CCL2 • CXCL10 • ICAM1 • IFNB1 • IFNG • IL10 • IL12A • IL6 • TYK2

VALOR: A Study to Investigate the Efficacy and Safety of Brepocitinib in Adults with Dermatomyositis (clinicaltrials.gov) - P3 | N=241 | Active, not recruiting | Sponsor: Priovant Therapeutics, Inc. | Trial completion date: Dec 2024 ➔ Jul 2026 | Trial primary completion date: Dec 2024 ➔ Jul 2025

Trial completion date • Trial primary completion date • Dermatomyositis • Immunology • Myositis