Litfulo (ritlecitinib)

P=N/A, N=850, Recruiting, Pfizer | N=450 --> 850

P=N/A, N=39, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=850 --> 39

P1, N=12, Completed, Pfizer | Active, not recruiting --> Completed

P=N/A, N=150, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P=N/A, N=450, Recruiting, Pfizer | Not yet recruiting --> Recruiting

P=N/A, N=450, Not yet recruiting, Pfizer

P3, N=600, Recruiting, Pfizer | Trial completion date: Jul 2025 --> Dec 2025 | Trial primary completion date: Jul 2025 --> Dec 2025

Anti-TNF agents, rituximab, and JAKi (particularly tofacitinib) can increase the risk of infections. Close monitoring of patients undergoing these therapies is recommended. Prospective studies with long-term follow-up are needed to comparatively evaluate the risks of infection deriving from treatment with BD and JAKi.

Ritlecitinib treatment was also not associated with an imbalanced incidence of neurological and audiological adverse events. These results provide evidence that the BAEP and axonal swelling finding in dogs are not clinically relevant in humans.

P1, N=6, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=12 --> 6

P3, N=400, Recruiting, Pfizer | Trial completion date: Aug 2026 --> Jan 2027 | Trial primary completion date: Aug 2026 --> Jan 2027

P2, N=71, Terminated, Pfizer | Phase classification: P2a --> P2 | Trial completion date: May 2026 --> May 2024 | Active, not recruiting --> Terminated; For business reasons

P=N/A, N=850, Recruiting, Pfizer | Not yet recruiting --> Recruiting

P1, N=12, Recruiting, Pfizer | Not yet recruiting --> Recruiting

P2, N=20, Recruiting, Icahn School of Medicine at Mount Sinai | Phase classification: P2a --> P2

P2, N=30, Recruiting, Icahn School of Medicine at Mount Sinai

The probabilities of achieving target modified clinical remission and endoscopic improvement outcomes at both weeks 8 and 52 for ritlecitinib 100 mg once daily was 74.8%. Model-based assessment mitigated some of the risk associated with proceeding to pivotal phase 3 trials with dosing regimens of which there was limited clinical experience.

P1, N=12, Not yet recruiting, Pfizer

P1, N=12, Completed, Pfizer | Recruiting --> Completed

P2, N=30, Recruiting, Massachusetts General Hospital | Trial completion date: Jan 2025 --> Aug 2025 | Trial primary completion date: Jan 2024 --> Aug 2025

P=N/A, N=850, Not yet recruiting, Pfizer

P1, N=12, Recruiting, Pfizer | Not yet recruiting --> Recruiting

P3, N=400, Recruiting, Pfizer | Not yet recruiting --> Recruiting

Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available).

Six drugs (abrocitinib, baricitinib, deucravacitinib, ritlecitinib, tofacitinib, upadacitinib) are used for the treatment of inflammatory diseases (atopic dermatitis, rheumatoid arthritis, psoriasis, alopecia areata, and ulcerative colitis)...The following seven drugs received FDA approval in 2023: capivasertib (HER2-positive breast cancer), fruquintinib (metastatic colorectal cancer), momelotinib (myelofibrosis), pirtobrutinib (mantle cell lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma), quizartinib (Flt3-mutant acute myelogenous leukemia), repotrectinib (ROS1-positive lung cancer), and ritlecitinib (alopecia areata). All of the FDA-approved drugs are orally effective with the exception of netarsudil, temsirolimus, and trilaciclib. This review summarizes the physicochemical properties of all 80 FDA-approved small molecule protein kinase inhibitors including the molecular weight, number of hydrogen bond donors/acceptors, polar surface area, potency, solubility, lipophilic efficiency, and ligand efficiency.

P2, N=244, Completed, Pfizer | Phase classification: P2a --> P2

P3, N=1450, Recruiting, Pfizer | Not yet recruiting --> Recruiting

P1, N=12, Not yet recruiting, Pfizer

Mild to moderate common adverse effects were observed, which included headache, nasopharyngitis, and upper respiratory tract infection. The recommended regimen of ritlecitinib capsules is 50 mg QD with without food and swallowed whole.

P3, N=400, Not yet recruiting, Pfizer

Few treatment options are available, with the Janus kinase (JAK) 1/2 inhibitor baricitinib (2022) and the selective JAK3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) inhibitor ritlecitinib (2023) being the only US Food and Drug Administration-approved systemic medications thus far for severe AA. This narrative review presents a detailed overview about the role of T cells and T-cell-signaling pathways in the pathogenesis of AA, with a focus on those pathways targeted by drugs in clinical development for the treatment of AA. A detailed summary of new drugs targeting these pathways with expert commentary on future directions for AA drug development and the importance of targeting multiple T-cell-signaling pathways is also provided in this review.

The present approach demonstrated the evolution of three population pharmacokinetic models with accumulating data, addressed clinical drug development questions related to systemic exposures of ritlecitinib, and informed the approved product label.

Approximately 10% of patients achieved response after >1 year suggesting that extended treatment may be benefit some patients. Evaluation of individual response profiles may identify patient and disease characteristics associated with treatment response.

P2a, N=244, Completed, Pfizer | Active, not recruiting --> Completed

P3, N=1450, Not yet recruiting, Pfizer

Ritlecitinib does not inhibit BCRP, OATP1B1, and OAT3 and is unlikely to cause a clinically relevant interaction through these transporters. Furthermore, our findings add to the body of evidence supporting the utility of CP-I and PDA as endogenous biomarkers for assessment of OATP1B1 and OAT1/3 transporter activity.

However, several novel therapies that specifically target the immunopathology of AA have emerged, including Janus kinase (JAK) 1/2 inhibitors such as baricitinib and deuruxolitinib, and the JAK3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor ritlecitinib...Pezalla is a paid consultant to Pfizer for market access and payer strategy concerns; Fung, Tran, Bourret, Takiya, Peeples-Lamirande, and Napatalung are employees of Pfizer and hold stock in Pfizer. This article was funded by Pfizer.

P2a, N=20, Recruiting, Icahn School of Medicine at Mount Sinai

These analyses represent a new methodology for generating reference HP cohorts in special population studies for drugs in development with well-characterized pharmacokinetics in HPs and adequate POPPK models. TRIAL REGISTRATION: ClinicalTrials.gov NCT04037865 , NCT04016077 , NCT02309827 , NCT02684760 , and NCT02969044 .

Based on the evaluation of the renal clearance of N -methylnicotinamide (NMN), ritlecitinib does not exert clinically meaningful inhibition on renal OCT2 or MATE1/2K. This study confirmed ritlecitinib and M2 are inhibitors of OCT1 but not OCT2 or MATE1/2K in healthy adults.

Four of 16 patients receiving brepocitinib achieved ≥30% improvement from baseline in Severity of Alopecia Tool score or better; 4 of 15 and 5 of 12 showed improvement in eyebrow and eyelash assessments, respectively. Although the small number of patients precludes firm conclusions regarding efficacy, the data suggest that some patients with alopecia areata and inadequate response to ritlecitinib after ≥24 weeks show benefit after switching to brepocitinib.

We targeted the key downstream IL2R-intermediate JAK 3 using a clinically relevant highly specific JAK3-inhibitor (JAK3i; PF-06651600) that potently inhibited STAT5-phosphorylation in vitro...Low-dose JAK3i combined with cellular and peptide vaccine strategies further decreased tumor load compared to both monotherapies alone. Collectively, these results identify JAK3 as a novel and promising target for combination immunotherapy.