In recent years, oral therapy with the JAK1/2 inhibitor ruxolitinib has become the standard of care. Since 2021, the JAK2/FLT3 inhibitor fedratinib has also been approved in the EU (note: in Switzerland, fedratinib will no longer be available as of February 28, 2025, as Swissmedic did not extend its time-limited approval)...Compared to the other two JAK inhibitors, momelotinib is particularly effective in patients with clinically symptomatic moderate to severe anemia. Results from studies investigating additional JAK inhibitors, combination therapies, and novel agents have also demonstrated significant efficacy and point toward future therapeutic developments, although these approaches are not yet available for routine clinical practice.

P1/2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P2/3, N=207, Active, not recruiting, Sobi Inc. | Recruiting --> Active, not recruiting

In the TQT study, 42 subjects received single doses of pacritinib 400 mg, moxifloxacin 400 mg (positive control), and placebo in a crossover design. Median QTcF changes from pre-dose to 4 h post-dose were minimal (+2.7 and -0.3 ms, respectively), and no dose-response relationship was identified. These findings suggest that pacritinib exposure is unlikely to be correlated with QT prolongation.

P1/2, N=4, Terminated, The University of Texas Health Science Center at San Antonio | N=44 --> 4 | Trial completion date: Sep 2027 --> May 2026 | Recruiting --> Terminated | Trial primary completion date: Sep 2027 --> May 2026; Investigational drug limitations

Perturbation-based screening identified multiple compounds capable of reversing these interferon-amplified signatures, and in vitro experiments demonstrated that alpinetin and momelotinib suppress interferon-γ signaling through distinct STAT1-and JAK-STAT-dependent mechanisms. irAEs may arise from the convergence of pre-existing myeloid inflammation and interferon-driven lymphocyte activation before therapy. Our study provides a predictive framework for identifying high-risk patients and highlights mechanistically grounded compounds for potential irAE mitigation.

Momelotinib demonstrated meaningful clinical benefit and acceptable safety in cytopenic patients pretreated with ruxolitinib, which supports its role after ruxolitinib failure.

P2/3, N=192, Not yet recruiting, GlaxoSmithKline

P1, N=20, Recruiting, University of Kansas Medical Center | Not yet recruiting --> Recruiting

P2, N=32, Not yet recruiting, Medical College of Wisconsin | Initiation date: Mar 2026 --> Jul 2026

P3, N=407, Active, not recruiting, Swedish Orphan Biovitrum | Recruiting --> Active, not recruiting | Trial completion date: Jul 2027 --> Oct 2028

P2, N=80, Recruiting, GlaxoSmithKline | N=56 --> 80