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

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

A Systematic Review of Pharmacological Interventions for Hidradenitis Suppurativa: A Focus on Clinical Response, Quality of Life, and Safety (ISPOR-EU 2024) - "Adalimumab, anakinra, apremilast, avacopan, bimekizumab, doxycycline, guselkumab, IFX-1, MABp1, PF-06650833, PF-06700841, PF-06826647, povorcitinib, risankizumab, RIST4721, secukinumab, upadacitinib all reported notable clinical benefits, with Hidradenitis Suppurativa Clinical Response (HiSCR) ranged from 10% (anakinra at week 24) to 88% (povorcitinib-90 mg at week 8)...In contrast, no SAEs were detected in spesolimab or anakinra, while bimekizumab had similar safety profiles to adalimumab. The results of this review demonstrate the possibility of highly personalized treatment approaches for HS management, including adalimumab and povorcitinib. The optimization of HS care requires further research on long-term outcomes."

Clinical • HEOR • Review • Dermatology • Hidradenitis Suppurativa • Immunology • Pain

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 | Active, not recruiting | Sponsor: Priovant Therapeutics, Inc. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Dermatomyositis • Immunology • Myositis

NEPTUNE: A Study of Brepocitinib in Adults with Active Non-Infectious Non-Anterior Uveitis (clinicaltrials.gov) - P2 | N=26 | Completed | Sponsor: Priovant Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Ocular Inflammation • Ophthalmology • Uveitis

Efficacy and Safety Profile of Small Molecules for Induction and Maintenance of Remission in Ulcerative Colitis: A Systematic Review of Randomised Control Trials (ACG 2024) - "Among 6845 pooled patients from 9 RCTs, small molecules (including tofacitinib, ritlecitinib,brepocitinib,upadacitinib,filgotinib,etrasimod) were superior to placebo in the management of UC for induction as well as maintenance of remission. These agents are effective resulting in early clinical remission, as determined by the assessment of total Mayo score and endoscopic normalization and they also help achieve corticosteroid-free remission. Further assessment showed significantly improved HRQoL and IBDQ (Inflammatory Bowel Disease Questionnaire) outcomes."

Clinical • Review • Anemia • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Bowel Disease • Pain • Ulcerative Colitis • Varicella Zoster

A phase 2a trial of brepocitinib for cicatricial alopecia. (PubMed, J Am Acad Dermatol) - "Brepocitinib significantly reduces CCL5 expression and was well tolerated at week 24, meeting co-primary endpoints. Brepocitinib reduces inflammatory biomarker expression and improves clinical severity, while maintaining favorable safety profile."

Journal • P2a data • Alopecia • Dermatopathology • Fibrosis • Immunology • Lichen Planus • CCL5 • IFNG • TYK2

CLARITY: A Study of Brepocitinib in Adults With Active, Non-Infectious, Non-Anterior Uveitis (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Priovant Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | N=220 ➔ 300 | Trial completion date: Aug 2027 ➔ Feb 2028

Enrollment change • Enrollment open • Trial completion date • Ocular Inflammation • Ophthalmology • Uveitis

Safety and Efficacy of Brepocitinib, a TYK2/JAK1 Inhibitor, in Active Noninfectious Uveitis: A 52-Week Phase 2 Study (NEPTUNE) (AAO 2024) - "Adverse event rate was similar in both arms. Conclusion Brepocitinib demonstrated dose-dependent, clinically meaningful efficacy and was well tolerated, with a safety profile consistent with prior brepocitinib studies and pharmacologic class."

Clinical • P2 data • Macular Edema • Ocular Inflammation • Ophthalmology • Uveitis • TYK2

Priovant Therapeutics Announces Receipt of Fast Track Designation from FDA for Brepocitinib in Non-Anterior Non-Infectious Uveitis (NIU) & Start of Enrollment of Brepocitinib Phase 3 NIU Program (PRNewswire) - "Priovant Therapeutics today announced that the first patients have been enrolled in CLARITY, a Phase 3 study evaluating brepocitinib in non-anterior non-infectious uveitis. Brepocitinib has also been granted Fast Track Designation for NIU by FDA. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need....Patient-level macular edema results at week 24 from the NEPTUNE Study will be presented at the American Academy of Ophthalmology (AAO) annual meeting October 18-21 in Chicago. Top-line 52-week Phase 2 data from NEPTUNE will also be available by the end of the year. In addition to NIU, brepocitinib is being evaluated in a fully enrolled Phase 3 study in dermatomyositis (VALOR). Top-line data from the VALOR Study is expected in the second half of 2025, with an NDA submission to follow if successful."

Fast track • P2 data • P3 data: top line • Trial status • Dermatomyositis • Immunology • Ophthalmology • Uveitis

The role of JAK/STAT signaling in neutrophilic airway inflammation (ERS 2024) - "Isolated neutrophils were pretreated with Brepocitinib, a TYK2-JAK1-JAK2 inhibitor, and further stimulated with IL-17 and IL-23 for migration... Our preliminary data indicates the involvement of the IL-23/IL-17 axis in neutrophilic airway inflammation and related corticosteroid resistance, highlighting the potential of JAK inhibitors as an additional therapeutic approach."

Chronic Obstructive Pulmonary Disease • Inflammation • Respiratory Diseases • IL17A • IL23A • TYK2

A DOSE-RANGING STUDY TO EVALUATE EFFICACY AND SAFETY OF PF-06700841 IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) (clinicaltrials.gov) - P2 | N=350 | Completed | Sponsor: Pfizer | Phase classification: P2b ➔ P2

Phase classification • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Validation of the Peak Pruritus-Numerical Rating Scale in patients with chronic plaque psoriasis: results from a phase 2 study. (PubMed, Int J Dermatol) - P2b | "PP-NRS is a reliable, practical test for assessing pruritus in mild-to-moderate PsO clinical trials."

Journal • P2 data • Dermatology • Immunology • Inflammation • Pruritus • Psoriasis

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. | Recruiting ➔ Active, not recruiting

Enrollment closed • Dermatomyositis • Immunology • Myositis

Priovant Therapeutics Announces Completion of Enrollment in Global Phase 3 Study Evaluating Brepocitinib in Dermatomyositis (VALOR) (PRNewswire) - "Priovant Therapeutics today announced completion of enrollment of the Phase 3 VALOR study evaluating brepocitinib in dermatomyositis. The study enrolled 241 subjects across 90 sites in four continents, making it the largest interventional dermatomyositis trial ever conducted....Data are anticipated in the second half of calendar year 2025, with a potential NDA submission to follow....Priovant expects to share 52-week top-line results from the NEPTUNE study and initiate an NDA-enabling Phase 3 program by the end of 2024."

Enrollment closed • New P3 trial • P2 data • P3 data • Amyotrophic Lateral Sclerosis • Dermatomyositis • Immunology • Uveitis

Brepocitinib, a potent and selective TYK2/JAK1 inhibitor: scientific and clinical rationale for dermatomyositis. (PubMed, Clin Exp Rheumatol) - "Therefore, there is a strong scientific and clinical rationale for the utility and potential effectiveness of brepocitinib in the treatment of DM patients. Currently, the safety, tolerability, and efficacy of brepocitinib is being evaluated in the largest (n=225) double-blind placebo-controlled phase 3 trial in DM patients to date (VALOR - NCT0543726)."

Journal • Review • Crohn's disease • Dermatology • Dermatomyositis • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hidradenitis Suppurativa • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Myositis • Orthopedics • Pain • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Ulcerative Colitis • IFNA1 • IFNG • IL12A • IL23A • TYK2

Therapeutic Potential of Targeting the JAK/STAT Pathway in Psoriasis: Focus on TYK2 Inhibition. (PubMed, J Clin Med) - "New molecules are currently under investigation for the treatment of psoriasis, such as deucravacitinib, an oral selective inhibitor that binds to the regulatory domain of TYK2, brepocitinib (PF-06700841) and PF-06826647 that bind to the active site in the catalytic domain. Due to the selective TYK2 blockade allowing the inhibition of key cytokine-mediated signals, such as those induced by IL-12 and IL-23, anti-TYK2 agents appear to be very promising as the safety profile seems to be superior compared with pan-JAK inhibitors. The aim of our review is to thoroughly explore the rationale behind the usage of JAK inhibitors in PsO, their efficacy and safety profiles, with a special focus on oral TYK2 inhibitors, as well as to provide a forward-looking update on novel therapeutic strategies targeting the TYK2 pathway in psoriasis."

Journal • Review • Cardiovascular • Dermatology • Immunology • Infectious Disease • Oncology • Psoriasis • Venous Thromboembolism • IL12A • IL23A • TYK2

UNRAVELING JAK/STAT3 ACTIVATION PATTERNS IN DERMATOMYOSITIS: IMPLICATIONS FOR UNDERSTANDING THE IFN-I SIGNALING PATHWAYS (EULAR 2024) - "Separated peripheral blood mononuclear cells (PMBC) were evaluated for phosphorylated STAT3 levels by fluorescence-activated cell sorting (FACS) analysis, both in CD4 pos and CD14 pos cells, before and after incubation in separated cultures with half-maximal inhibitory concentration (IC50) of abrocitinib, gandotinib, peficitinib, or deucravacitinib (Biovision Inc. The JAK/STAT3 pathway is significantly activated in patients affected by DM. Specifically, DM patients presented a high activation of pSTAT3 that was modified mainly by direct inhibition of JAK-1 and especially TYK-2 in both lymphocytes and monocytes, thus modulating IFN-I effects. Our findings, to be confirmed in larger studies also evaluating phosphorylation of other STATs, pave the way for the clinical use of JAK-inhibitors in DM patients [3], in particular acting on JAK-1/TYK-2 such as the new brepocitinib."

Dermatomyositis • Immunology • Myositis • CD14 • JAK1 • JAK2 • JAK3 • STAT3 • TYK2

Exploring Janus kinase inhibitors for alopecia areata: a comprehensive review. (PubMed, Ital J Dermatol Venerol) - "Collectively, the reviewed studies affirm JAK inhibitors, particularly Baricitinib, as promising treatments for moderate to severe alopecia areata. These inhibitors exhibit superior efficacy, as indicated by notable reductions in SALT scores, and are well-tolerated, with predominantly mild and manageable adverse events."

Journal • Review • Alopecia • Immunology