Myeloproliferative Neoplasms Clinical Trial Landscape

The myeloproliferative neoplasm trial landscape in 2026

Myeloproliferative neoplasms — a family of clonal stem cell disorders including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) — have seen sustained drug development investment driven by the validated JAK-STAT pathway and the chronic, treatable nature of these diseases. Ruxolitinib (Jakafi) established JAK1/2 inhibition as the backbone of MF and PV treatment. Now, the field is moving in two directions simultaneously: combination regimens for harder-to-treat patients, and new mechanisms targeting the root driver — the JAK2 V617F mutation present in the majority of ET, PV, and MF patients.

In 2026, fifteen trials are actively recruiting across the MPN spectrum. Three Phase 3 trials are underway in ET and PV. Incyte — the originator of ruxolitinib — has four simultaneous Phase 1 programs pursuing next-generation MPN assets, suggesting the company is building a post-ruxolitinib pipeline. Merck has two Phase 3 trials for bomedemstat, an LSD1 inhibitor, in ET.

For hematology BD teams and oncology investors, MPNs are a commercially validated indication with a growing pipeline of combination and next-generation agents. The chronic disease course creates durable commercial opportunities — patients stay on therapy for years, and new mechanisms that improve on JAK inhibitor limitations (resistance, transformation) command significant pricing.

Current MPN trial activity (as of early 2026)

Based on ClinicalTrials.gov data updated daily by DataLookout:

The MPN competitive landscape in 2026

Bomedemstat (Merck) — LSD1 inhibition enters Phase 3 in ET

Merck's bomedemstat (MK-3543) is the most clinically advanced new mechanism in the MPN field. An inhibitor of LSD1 (lysine-specific demethylase 1), bomedemstat works through a fundamentally different pathway than JAK inhibitors — it targets epigenetic regulation of hematopoiesis rather than cytokine signaling. In ET, where JAK inhibitors are rarely used as first-line therapy, bomedemstat is being positioned as an alternative or complement to hydroxyurea in a head-to-head Phase 3 study (NCT06456346) and a broader efficacy trial (NCT06351631).

Two simultaneous Phase 3 trials in ET — both Merck-sponsored — is an unusual investment for a non-JAK mechanism. It signals Merck's confidence that LSD1 inhibition can address a distinct patient population in ET, potentially those who are hydroxyurea-intolerant or -resistant. For BD teams: bomedemstat's Phase 3 data are the most commercially significant readout in the MPN field expected in the 2026–2027 timeframe.

AVAJAK — anticoagulation for JAK2 V617F: the preventive angle

The AVAJAK study (NCT05198960) takes a structurally different approach from all other MPN trials: rather than targeting the MPN clone itself, it asks whether anticoagulation (apixaban or rivaroxaban vs. aspirin) can prevent the thromboembolic events that cause most MPN morbidity. JAK2 V617F-positive MPNs carry elevated thrombosis risk independent of hematocrit or platelet count — a risk not fully mitigated by cytoreduction or aspirin alone.

If AVAJAK demonstrates superiority of direct oral anticoagulants over aspirin in JAK2 V617F-positive MPN patients, it would change prescribing practice for hundreds of thousands of patients — not through a new drug, but through a new application of existing anticoagulants. For pharma BD teams, this trial is a signal of growing recognition that MPN management extends beyond cytoreduction.

Incyte's Phase 1 MPN pipeline — four simultaneous programs

Incyte Corporation, which owns ruxolitinib (Jakafi), is running four simultaneous Phase 1 studies in MPNs in 2026. This is a striking concentration of early-stage investment from a single sponsor:

• INCA035784 (NCT07008118) — initiated October 2025; mechanism undisclosed in public registration
• INCB160058 (NCT06313593) — initiated August 2024; early safety data expected 2025–2026
• INCA036978 (NCT07441694) — initiated March 2026; the most recently launched Incyte MPN program
• INCA033989 (NCT06034002) — initiated December 2023; in monotherapy and combination with ruxolitinib arms

Incyte running ruxolitinib combination trials for its own Phase 1 MPN assets is a strategic pattern: the company is building combination regimens on top of its own approved drug, which reduces partner dependency and preserves commercial control. For competitors and BD teams, the INCA033989 combination arm is particularly notable — it suggests Incyte believes its next generation MPN assets work best alongside ruxolitinib, not as replacements.

JNJ-88549968 (Janssen) — targeting CALR-mutated MPN

Janssen's JNJ-88549968 (NCT06150157) is the only program in the current recruiting MPN landscape specifically targeting CALR-mutated disease. Approximately 25–30% of ET patients and 20–25% of MF patients carry CALR mutations rather than JAK2 V617F. These patients have a distinct biology and, historically, fewer targeted therapy options — most approved JAK inhibitors were developed with JAK2 V617F as the primary driver population.

A CALR-specific program from Janssen represents a precision medicine bet: if CALR-targeting proves efficacious, it could define a commercially significant subpopulation with high unmet need and a clear biomarker-selected population — the model that has worked in precision oncology broadly.

Inflammation as a driver — canakinumab in myelofibrosis

The canakinumab study in myelofibrosis (NCT05467800) tests an IL-1β antibody in MF — an inflammatory biology hypothesis. Novartis's canakinumab demonstrated cardiovascular benefit in the CANTOS trial through IL-1β inhibition. The hypothesis in MF: inflammatory cytokines drive constitutional symptoms and potentially disease progression. An IL-1β antibody could address the inflammatory component of MF independently of JAK-STAT pathway activity, potentially in combination with ruxolitinib. This represents a mechanistically distinct hypothesis from every other MPN trial in 2026.

What DataLookout monitors for myeloproliferative neoplasms

Configure your profile with condition and mechanism keywords for targeted MPN monitoring:

• By condition: "myeloproliferative neoplasm", "essential thrombocythemia", "polycythemia vera", "MPN", "ET trial", "PV trial"
• By mechanism: "LSD1 inhibitor MPN", "bomedemstat", "JAK2 V617F", "CALR mutation", "ruxolitinib combination"
• By program: "INCA033989", "INCA035784", "INCB160058", "INCA036978", "JNJ-88549968" for Incyte and Janssen program tracking
• By disease stage: "blast phase MPN", "accelerated phase myeloproliferative", "MPN transformation" for transformation-focused monitoring
• By sponsor: "Incyte MPN", "Merck myeloproliferative", "Janssen CALR" for company-specific intelligence

Who uses MPN trial monitoring

Hematology-focused BD teams

Business development teams at pharma companies with hematology franchises are watching the MPN landscape for in-licensing opportunities in validated mechanisms. Incyte's four Phase 1 programs will generate first-in-human data in 2025–2026 — early datapoints that trigger licensing interest if safety and early PD signals are positive. Bomedemstat's Phase 3 readout is the field-defining event: a positive result would prove LSD1 inhibition in MPN and potentially open combination opportunities with established JAK inhibitors.

Oncology investors and portfolio managers

MPN stocks — particularly Incyte and companies developing bomedemstat alternatives — are sensitive to trial milestones. Protocol amendments, enrollment completion signals, and new Phase 1 registrations on ClinicalTrials.gov precede press releases. Incyte's simultaneous four-program Phase 1 push is a signal of pipeline confidence that matters for investment thesis construction. Daily monitoring ensures trial signals are caught early.

Medical affairs and HEOR teams

Medical affairs teams at JAK inhibitor companies need daily visibility into competitive pipeline activity to anticipate new entrants, combination strategies, and treatment algorithm evolution. Health economics teams modeling MPN treatment pathways need to understand where bomedemstat, CALR-targeting, and combination regimens would fit relative to existing standards of care. The granular trial data from ClinicalTrials.gov — phases, arms, eligibility criteria — informs both strategic and economic planning.

Frequently asked questions