ropsacitinib (PF-06826647) / Pfizer, Priovant Therap - LARVOL DELTA

The Efficacy and Safety of Oral Biologics and Small Molecule Inhibitors for Moderate to Severe Plaque Psoriasis: A Systematic Review and Network Meta-Analysis (EADV 2026) - "Introduction Systemic options for moderate-to-severe plaque psoriasis have expanded with the development of oral small molecule inhibitors, including PDE4 inhibitors (apremilast, orismilast, roflumilast), TYK2 inhibitors (deucravacitinib, zasocitinib, envudeucitinib, ropsacitinib), and the first-in-class oral IL-23 receptor inhibitor icotrokinra. Among interventions with a more robust evidence base, icotrokinra 200 mg/day and deucravacitinib 6 mg/day demonstrated substantially greater efficacy than apremilast with comparable safety. Larger head-to-head trials and longer follow-up are needed to confirm the standing of the newer oral treatments."

Retrospective data • Review • Dermatology • Immunology • Plaque Psoriasis • Psoriasis • IL23A • TYK2

Deep learning–based prediction of TYK2 inhibitor potency: correlating Boltz-2 outputs with experimental IC50 data | Poster Board #1398 (ACS-Fall 2026) - "This study evaluates Boltz-2 by comparing its predictions against experimental TYK2 IC50 values for the clinical candidate PF-06826647 and its analogs... These findings position Boltz-2 as a robust and computationally efficient tool for TYK2 lead optimization, broader SAR analysis, and the identification of novel chemical entities in drug discovery"

IL12A • IL23A • TYK2

Deep learning–based prediction of TYK2 inhibitor potency: correlating Boltz-2 outputs with experimental IC50 data | Poster Board #1740 (ACS-Fall 2026) - "This study evaluates Boltz-2 by comparing its predictions against experimental TYK2 IC50 values for the clinical candidate PF-06826647 and its analogs... These findings position Boltz-2 as a robust and computationally efficient tool for TYK2 lead optimization, broader SAR analysis, and the identification of novel chemical entities in drug discovery"

IL12A • IL23A • TYK2

Emerging synthetic drugs for the management of Hidradenitis Suppurativa: a comprehensive update. (PubMed, Expert Opin Pharmacother) - "Currently, only three biologic agents - adalimumab, secukinumab, and bimekizumab - hold regulatory approval for moderate-to-severe HS...Mechanistic classes discussed include Janus kinase (JAK) inhibitors (povorcitinib, upadacitinib, ruxolitinib), TYK2 inhibitors (brepocitinib, ropsacitinib, deucravacitinib), PDE-4 inhibitors (apremilast, orismilast, roflumilast), BTK/SYK inhibitors (remibrutinib, fostamatinib), IRAK-4 inhibitors (zimlovisertib), and HSP-90 inhibitors (RGRN-305)...The emergence of topical JAK inhibitors (ruxolitinib cream) for milder HS and the progression of BTK inhibitors (remibrutinib) to Phase 3 trials signal a broadening treatment landscape. Personalized selection of synthetic drugs versus biologics - informed by patient comorbidities, disease phenotype, and biomarkers - will be involved in next-generation HS management."

Journal • Review • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation • IRAK4 • JAK1 • SYK • TYK2

Identification of senescence-related genes in Parkinson's disease reveals candidate therapeutic targets and pathological processes. (PubMed, Animal Model Exp Med) - "Overall, this study demonstrates that D-gal-induced aging-like stress accelerates PD-related pathological progression by activating multiple signaling pathways, including JAK-STAT, AGE-RAGE, and NF-κB, thereby promoting inflammation, oxidative stress, and neuronal dysfunction. Key genes including IRF7 may serve as candidate biomarkers, providing preliminary evidence for the role of senescence-like stress in PD pathogenesis."

Journal • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • BCL6 • IFNG • IL17A • IRF7 • SYK • TYK2

Large-scale meta-analysis of infection risk with JAK-STAT inhibitors in 29,000 patients. (PubMed, J Eur Acad Dermatol Venereol) - "This meta-analysis provides a comprehensive assessment of the risk of infection associated with JAK-STAT inhibitors in IMIDs of the skin. Although overall safety is acceptable, clinicians should be aware of the higher infection risk of influenza and herpes zoster and should consider vaccination and preventive strategies for high-risk patients with atopic dermatitis. The main limitation is that the included studies involved highly selected populations with few comorbidities and short follow-up."

Journal • Retrospective data • Review • Alopecia • Atopic Dermatitis • Dermatitis • Dermatology • Herpes Zoster • Immunology • Infectious Disease • Inflammation • Influenza • Pulmonary Disease • Respiratory Diseases • Varicella Zoster • Vitiligo

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

Efficacy and Safety of Medical Interventions for Moderate to Severe Hidradenitis Suppurativa: A Living Systematic Review and Network Meta-Analysis. (PubMed, JAMA Dermatol) - "Compared with placebo, the following treatments were associated with significantly higher HiSCR-50 response rates: sonelokimab, 120 mg, every 4 weeks; lutikizumab, 300 mg, every 2 weeks; adalimumab, 40 mg, once per week; sonelokimab, 240 mg, every 2 weeks; bimekizumab, 320 mg, every 2 weeks; povorcitinib, 15 mg, once per day; bimekizumab, 320 mg, every 4 weeks; secukinumab, 300 mg, every 4 weeks; and secukinumab, 300 mg, every 2 weeks. The percentage of patients discontinuing treatment due to adverse events ranged from 0% to 10% in the placebo groups, 0% to 4% in the adalimumab (40 mg, once per week) groups, and 0% to 15% (ropsacitinib) in the other active treatment groups. This network meta-analysis provides evidence for the comparative efficacy and safety of currently approved and pipeline medications for moderate to severe HS in the absence of head-to-head trials."

Clinical • Journal • Retrospective data • Dermatology • Hidradenitis Suppurativa • Immunology

Pharmacological Management of Psoriasis: Current Landscape and Future Perspectives. (PubMed, Recent Adv Inflamm Allergy Drug Discov) - "Numerous novel synthetic agents, such as JAK/STAT inhibitors [ruxolitinib, peficitinib], TYK2 inhibitors [zasocitinib, ropsacitinib], RORꝩT inhibitors [cedirogant], A3AR agonists [piclodenoson], and CXCR2 antagonists [vimnerixin] are undergoing extensive clinical trials and have demonstrated beneficial outcomes in multiple phases of these trials. Deucravacitinib, an orally administered TYK2 inhibitor, has recently received FDA approval for the treatment of moderate to severe plaque psoriasis...Moreover, these pathways can be exploited to personalize anti-psoriatic therapy, minimize side effects, and maximize therapeutic outcomes. Altogether, the integration of biological agents and synthetic agents can overcome the challenges associated with the management of the repertoire of psoriatic pathophysiology and symptoms."

Journal • Dermatology • Immunology • Inflammation • Psoriasis • CXCR2 • IL23A • TYK2

A systematic review of the efficacy of TYK2 inhibitors in patients with dermatological disease. (PubMed, Australas J Dermatol) - "Results indicate that Deucravacitinib is superior to placebo, Apremilast and Adalimumab in treating adult patients with moderate-to-severe plaque psoriasis and superior to placebo in the treatment of adults with systemic lupus erythematosus. Ropsacitinib demonstrated superiority over placebo in the management of plaque psoriasis. Brepocitinib and Ropsacitinib had more side effects than Deucravacitinib."

Journal • Review • Alopecia • Atopic Dermatitis • Dermatitis • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammatory Arthritis • Lupus • Psoriasis • Systemic Lupus Erythematosus • TYK2

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

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

TYK2: an emerging therapeutic target in rheumatic disease. (PubMed, Nat Rev Rheumatol) - "Various inhibitors of TYK2 have now been studied in human disease, and one of these inhibitors, deucravacitinib, has now been approved for the treatment of psoriasis. Two other inhibitors of TYK2, brepocitinib and ropsacitinib, are also in earlier stages of clinical trials. Overall, TYK2 inhibitors hold promise for the treatment of a distinct spectrum of autoimmune diseases and could potentially have a safety profile that differs from other JAK inhibitors."

Journal • Review • Dermatology • Dermatomyositis • Immunology • Inflammatory Arthritis • Lupus • Myositis • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Systemic Lupus Erythematosus • IL10 • IL12A • IL23A • JAK1 • JAK2 • JAK3 • TYK2

Brepocitinib, Zimlovisertib, and Ropsacitinib in Hidradenitis Suppurativa. (PubMed, NEJM Evid) - "At 16 weeks, only brepocitinib, a JAK1/TYK2 inhibitor, achieved a higher clinical response than placebo (52% vs. 33%). The other two agents were no better than placebo."

Journal • Dermatology • Hidradenitis Suppurativa • Immunology • JAK1 • TYK2

Oral small-molecule tyrosine kinase 2 and phosphodiesterase 4 inhibitors in plaque psoriasis: a network meta-analysis. (PubMed, Front Immunol) - "The study found that deucravacitinib at any dose (except for 3 mg QOD), ropsacitinib (200 and 400 mg QD), and apremilast (20 and 30 mg BID) had higher PASI and PGA response rates than placebo. More large-scale, long-term studies focusing on novel TYK2 inhibitors are needed. PROSPERO (ID: CRD42022384859), available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022384859, identifier CRD42022384859."

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

Development and Therapeutic Implications of Tyrosine Kinase 2 Inhibitors. (PubMed, J Med Chem) - "Substantial efforts have been made to develop selective TYK2 inhibitors: Deucravacitinib (BMS-986165) is a representative allosteric inhibitor that has been approved by the FDA, and ropsacitinib (PF-06826647) is an active site-directed inhibitor currently being evaluated in clinical trials. Herein, we outline the key roles of TYK2 in diseases, review the advances of selective TYK2 inhibitors, and finally discuss future perspectives and challenges in the development of TYK2 inhibitors."

Journal • Review • Immunology • TYK2

Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors. (PubMed, Dermatol Ther (Heidelb)) - "Two other tyrosine kinase 2 inhibitors in later stage clinical development, brepocitinib (PF-06700841) and ropsacitinib (PF-06826647), are orthosteric inhibitors that target the highly conserved catalytic domain. Two phase 3 psoriasis trials demonstrated deucravacitinib was efficacious and not associated with safety concerns characteristic of Janus kinase inhibitors, hence the new class designation (TYK2 inhibitor) by health authorities in the USA and Japan. Allosteric tyrosine kinase 2 inhibitors represent a promising new class of molecules for the treatment of psoriasis and psoriatic arthritis, and longer-term trials will establish their place in therapy."

Journal • Review • Dermatology • Immunology • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Pustular Psoriasis • Rheumatology • Seronegative Spondyloarthropathies • IL17A • TYK2

Clinical Implications of Targeting the JAK-STAT Pathway in Psoriatic Disease: Emphasis on the TYK2 Pathway. (PubMed, J Cutan Med Surg) - "Phase III efficacy and safety data for the selective allosteric TYK2-inhibitor, deucravacitinib, in adult patients with moderate-to-severe plaque psoriasis is promising. Furthermore, phase II clinical trials for ropsacitinib (PF-06826647), a selective TYK2 inhibitor, and brepocitinib (PF-06700841), a JAK1/TYK2 inhibitor, have also demonstrated efficacy and an acceptable safety profile in adult patients with moderate-to-severe plaque psoriasis. Other novel TYK2 allosteric inhibitors, NDI-034858 and ESK-001, are currently being investigated in adult patients with plaque psoriasis. This article reviews the details of the JAK-STAT pathway in psoriasis pathophysiology, the rationale for selective targeting of JAKs in the treatment of psoriasis, and provides clinical perspective on clinical trial data for JAK and TYK2 inhibitors."

Journal • Dermatology • Immunology • Inflammation • Psoriasis • IL12A • IL17A • IL23A • JAK1 • TYK2

Tyrosine Kinase 2 and Janus Kinase‒Signal Transducer and Activator of Transcription Signaling and Inhibition in Plaque Psoriasis. (PubMed, J Am Acad Dermatol) - "Deucravacitinib, an oral, selective inhibitor that binds to the regulatory domain of TYK2, and brepocitinib (PF-06700841) and PF-06826647, topical and oral TYK2 inhibitors, respectively, that bind to the active (adenosine triphosphate-binding) site in the catalytic domain, are in development for psoriasis. Selective, allosteric inhibition of TYK2 signaling may reduce the potential for toxicities associated with pan-JAK inhibitors. This article reviews JAK-STAT and TYK2 signaling, and the efficacy and safety of JAK inhibitors in psoriasis to date, focusing specifically on TYK2 inhibitors."

Journal • Review • Dermatology • Gastrointestinal Disorder • Immunology • Inflammation • Psoriasis • IFNAR2 • JAK1 • TYK2

Efficacy and Safety of Oral Tyrosine Kinase 2 Inhibitor PF-06826647 in Managing Moderate to Severe Plaque Psoriasis (PracticeUpdate) - "In the quest to have a more perfect drug to treat our psoriasis patients, a new mechanism of action-the inhibition of the tyrosine kinase pathway-is being explored...Our patients will need to let us know how they feel about switching to an oral agent with comparable efficacy to some of our biologics, but one that requires daily administration and carries some possible side-effect risks. Psoriasis patients will at the very least appreciate the additional option."

Online posting

From Pfizer and Roivant was born Priovant Therapeutics, specialized in anti-inflammatory drugs [Google translation] (Daily Health Industry) - "Pfizer and Roivant Sciences formed Priovant Therapeutics, an anti-inflammatory drug development company. The new biotech will initially promote two Pfizer treatments for autoimmune diseases: big pharma USA will own 25% of Priovant. The first drug from Pfizer is brepocitinib...The second drug under the agreement, ropsacitinib, is an anti-inflammatory that targets the TYK2 protein."

M&A • Immunology • Inflammatory Bowel Disease

Real Promise for JAK-inhibitors That Target TYK2 (MedPageToday) - "Andrew Blauvelt, MD, MBA...Blauvelt recently discussed the review and its findings with the Reading Room. The exchange has been edited for length and clarity....Blauvelt: Deucravacitinib (an oral once-daily pill) is the TYK2 blocker that is farthest along in clinical development and will likely be approved by the FDA within the next year. More TYK2 blockers are in the pipeline, including topical TYK2."

Media quote

Oral tyrosine kinase 2 inhibitor PF-06826647 demonstrates efficacy and an acceptable safety profile in participants with moderate-to-severe plaque psoriasis in a phase 2b, randomized, double-blind, placebo-controlled study. (PubMed, J Am Acad Dermatol) - P2 | "PF-06826647 200 and 400 mg QD showed significant efficacy versus placebo at week 16 and was well tolerated over 40 weeks."

Clinical • Journal • P2b data • Dermatology • Immunology • Psoriasis • TYK2

A Study to Evaluate the Safety and Efficacy of PF-06650833, PF-06700841, and PF 06826647 in Adults With Hidradenitis Suppurativa (clinicaltrials.gov) - P2a | N=197 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion • Acne Vulgaris • Dermatology • Hidradenitis Suppurativa

[VIRTUAL] A Phase 2b, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of the oral TYK2 inhibitor PF-06826647 in participants with plaque psoriasis (EADV 2021) - No abstract available

Clinical • P2b data • Dermatology • Immunology • Psoriasis • TYK2