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

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

Comparative efficacy and safety of JAK inhibitors in the treatment of moderate-to-severe alopecia areata: a systematic review and network meta-analysis. (PubMed, Front Pharmacol) - "Two low-dose groups of oral formulations (ritlecitinib 10mg and ivarmacitinib 2mg) and two topical formulations (delgocitinib ointment and ruxolitinib cream) appeared to be relatively ineffective against moderate-to-severe AA...Regarding the SALT50 response, brepocitinib 30mg ranked highest (sucra = 0.9567), followed by ritlecitinib 50mg (sucra = 0.8689) and deuruxolitinib 12mg (sucra = 0.7690)...To enhance the applicability and accuracy of our research, further head-to-head trials with longer follow-up periods are needed. Systematic Review Registration: identifier [CRD42022368012]."

Retrospective data • Review • Alopecia • Immunology

Pharmacokinetic Profile of Brepocitinib with Topical Administration in Atopic Dermatitis and Psoriasis Populations: Strategy to Inform Clinical Trial Design in Adult and Pediatric Populations. (PubMed, Pharm Res) - "The relationship between the amount of active drug applied and brepocitinib systemic CTrough, described by LMER, may inform the development strategy for dose optimization in the brepocitinib topical program."

Journal • PK/PD data • Atopic Dermatitis • Dermatitis • Dermatology • Hematological Disorders • Immunology • Pediatrics • Psoriasis • TYK2

Risk-Benefit Appraisal of Systemic JAK Inhibitors for Alopecia Areata: A Comprehensive Meta-Analysis Assessing Safety and Adverse Effects (ISDS 2023) - "Studies incorporated systemic JAK inhibitors in adults: Tofacitinib (JAK 1/3), Ruxolitinib (JAK 1/2), Baricitinib (JAK 1/2), Ritlecitinib (JAK 3), Brepocitinib (JAK 1/TYK2), and Deuruxolitinib (JAK 1/2)...Headache was reported with Deucravacitinib users being the most affected (20.95%)... While JAK inhibitors have side effects like headaches and acne, their therapeutic potential is considerable. The OR for common side effects, notably URI, showed an above 6-fold increase compared to placebos. Nevertheless, the data underscores a restrained risk for severe adverse events."

Adverse events • Retrospective data • Acne Vulgaris • Alopecia • Cardiovascular • Dyslipidemia • Herpes Zoster • Hypertriglyceridemia • Immunology • Infectious Disease • Metabolic Disorders • Myocardial Infarction • Nephrology • Pain • Respiratory Diseases • Varicella Zoster • JAK1 • JAK2 • JAK3 • TYK2

Adverse events in patients treated with Jak-inhibitors for alopecia areata: a systematic review (WCD 2023) - " Of 407 studies retrieved, 28 articles met the requirements and were used in our review, overall 1719 patients were included and the safety of 6 JAK-I was assessed (baricitinib, brepocitinib, deuruxolitinib, ritlecitinib, ruxolitinib, tofacitinib)... The AEs in AA patients receiving JAK-I are mostly mild and self-limited and predominantly consist of an increased risk of infections and laboratory abnormalities. No fatal outcomes or thromboembolism events have been reported"

Adverse events • Clinical • Review • Alopecia • Cardiovascular • Dermatology • Gastroenterology • Hematological Disorders • Infectious Disease • Myocardial Infarction • Neutropenia • Urology

Can brepocitinib be formulated into an effective topical therapy to treat mild-to-moderate chronic plaque psoriasis? (PubMed, Br J Dermatol) - No abstract available

Journal • Dermatology • Immunology • Psoriasis

Adverse events in patients treated with Jak-inhibitors for alopecia areata: a systematic review. (PubMed, J Eur Acad Dermatol Venereol) - "Of 407 studies retrieved, 28 papers met the requirements and were used in our review, including 5 RCTs and 23 case series, overall 1719 patients were included and the safety of 6 JAK-I was assessed (baricitinib, brepocitinib, deuruxolitinib, ritlecitinib, ruxolitinib, tofacitinib)...AEs reported with topical formulation included scalp irritation and folliculitis. The main limit of this review is the lack of data related to post-marketing surveillance, which should be maintained on a long-term basis."

Adverse events • Journal • Review • Alopecia • Cardiovascular • Dermatology • Gastroenterology • Hematological Disorders • Infectious Disease • Myocardial Infarction • Neutropenia • Urology

Efficacy and safety of topical brepocitinib cream for mild-to-moderate chronic plaque psoriasis: a phase IIb, randomised, double-blind, vehicle-controlled, parallel-group study. (PubMed, Br J Dermatol) - P2b | "Topical brepocitinib was well-tolerated but did not result in statistically significant changes vs. vehicle when administered at the doses evaluated to treat signs and symptoms of mild-to-moderate PsO."

Journal • P2b data • Dermatology • Herpes Zoster • Immunology • Inflammation • Pruritus • Psoriasis • Varicella Zoster • TYK2

How will brepocitinib cream compare with established treatments for mild-to-moderate eczema? (PubMed, Br J Dermatol) - No abstract available

Journal • Atopic Dermatitis • Dermatology • Immunology

The efficacy and safety of JAK inhibitors for alopecia areata: A systematic review and meta-analysis of prospective studies. (PubMed, Front Pharmacol) - "Subgroup analyses indicate that baricitinib, ritlecitinib and brepocitinib seem to have equal efficacy for AA in RCTs; ruxolitinib (vs. tofacitinib) and AA (vs. AT/AU) are associated with better efficacy outcomes in non-RCT. Due to the high recurrence rate after withdrawal of JAK inhibitors, continuous treatment should be considered to maintain efficacy. Systematic Review Registration: PROSPERO: CRD 42022303007."

Retrospective data • Review • Alopecia

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 topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: a phase IIb, randomised, double-blind, vehicle-controlled, dose-ranging, and parallel-group study. (PubMed, Br J Dermatol) - P2b | "Topical brepocitinib is effective and well tolerated in participants with mild-to-moderate AD. This trial is registered with clinicaltrials.gov and with EudraCT (2018-003050-24)."

Journal • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Gastrointestinal Disorder • Immunology • TYK2

A Scoping Review on Use of Drugs Targeting the JAK/STAT Pathway in Psoriasis. (PubMed, Front Med (Lausanne)) - "Nine different drugs administered through various routes were identified (systemic: peficitinib, baricitinib, solcitinib, itacitinib, abrocitinib, deucravacitinib, and brepocitinib; topical: ruxolitinib; and both: tofacitinib)...Only tofacitinib and deucravacitinib have undergone phase III clinical trials, being the only ones tested with active comparators etanercept and apremilast, respectively...Psoriasis treatment is currently symptomatic and could potentially present a significant risk of toxicity. Therefore, the design of principal efficacy outcome measures considering the impact of the outcome on quality of life and a drug assessment methodology aimed at improving safety would probably strengthen the evidence and decision-making process."

Clinical • Review • Dermatology • Immunology • Infectious Disease • Psoriasis • Respiratory Diseases

New Topical Therapies for Psoriasis. (PubMed, Am J Clin Dermatol) - "Tapinarof, an aryl hydrocarbon receptor inhibitor, has completed a phase III study and demonstrated good efficacy results, even in long treatment courses, with a favourable safety profile...Roflumilast, a phosphodiesterase type 4 inhibitor, also underwent a phase III study with significant lesion improvement and notable pruritus management, and with no reported side effects...The Janus kinase-signal transducer and activator of transcription pathway has been targeted in recent clinical investigations with promising options, currently with brepocitinib pending phase IIb results. Ongoing preclinical studies involving interleukin-2 inhibition, RNA modulators and amygdalin analogues may lead to forthcoming clinical trials. New topical drugs are successfully emerging and future research comparing them to classical options will dictate their clinical role in the treatment of psoriasis."

Journal • Dermatology • Immunology • Pruritus • Psoriasis • IL2

Dose Ranging Study To Assess Efficacy, Safety and Tolerability Of PF-06700841 Topical Cream In Psoriasis (clinicaltrials.gov) - P2b; N=344; Completed; Sponsor: Pfizer; Recruiting ➔ Completed; N=240 ➔ 344

Clinical • Enrollment change • Trial completion • Dermatology • Immunology • Psoriasis

[VIRTUAL] A Phase 2b study to evaluate the efficacy and safety of the topical TYK2/JAK1 inhibitor brepocitinib for mild-to-moderate atopic dermatitis (EADV 2020) - No abstract available

Clinical • Late-breaking abstract • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • TYK2

Pfizer Investor Day Features Significant Number of Pipeline Advances for COVID-19 Programs and Across Numerous Therapeutic Areas (Streetinsider.com) - P2a, N=292; "Key updates included: Phase 2 data were presented from a proof-of-concept study for topical brepocitinib...in patients with mild-to-moderate atopic dermatitis. A Phase 2a randomized, placebo-controlled study to evaluate efficacy and safety of topical brepocitinib in 292 patients with mild-to-moderate atopic dermatitis showed strong dose-dependent efficacy with 42% of those treated with the 3% once-daily brepocitinib topical achieving at least a 90% or greater change from baseline in their Eczema Area and Severity Index (EASI-90) score by week six."

P2a data • Immunology

Dose Ranging Study To Assess Efficacy, Safety and Tolerability Of PF-06700841 Topical Cream In Psoriasis (clinicaltrials.gov) - P2b; N=240; Recruiting; Sponsor: Pfizer; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Dermatology • Dermatopathology • Immunology • Psoriasis