CLINICAL TRIALS PROFILE FOR MIDOSTAURIN

All Clinical Trials for MIDOSTAURIN

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00045942 ↗	PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinas	Completed	Dana-Farber Cancer Institute	Phase 1/Phase 2	2002-01-30	CPKC412A2104 core had a 2 stage design. In stage 1, eight participants were treated. If at least one participant showed a clinical response, four more participants were recruited to stage 2. The trial was to be stopped if no participants showed a response in stage 1. POC was achieved if at least 2 participants out of 12 responded. In PKC412A2104E1, participants with AML or high risk MDS with wild-type or mutant FTL3 who had not previously received a FLT3 inhibitor were randomized to receive continuous twice daily oral doses of either 50 or 100 mg midostaurin in 1 28-day cycle regimen. Participants were to be treated until disease progression or the occurrence of unacceptable treatment-related toxicity. PKC412A2104 E2 contained 2 dosing regimens: 1) intra-participant midostaurin dose escalation and 2) midostaurin with itraconazole in participants with AML and high risk MDS irrespective of FLT3 status. Eligible participants were alternately assigned to the regimens. At the Investigator's discretion, intra-participant dose escalation was allowed for any previously enrolled CPKC412A2104E1 participant receiving midostaurin at the time of the approval of amendment 4. Participants were treated until the time of disease progression.
NCT00045942 ↗	PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinas	Completed	Memorial Sloan Kettering Cancer Center	Phase 1/Phase 2	2002-01-30	CPKC412A2104 core had a 2 stage design. In stage 1, eight participants were treated. If at least one participant showed a clinical response, four more participants were recruited to stage 2. The trial was to be stopped if no participants showed a response in stage 1. POC was achieved if at least 2 participants out of 12 responded. In PKC412A2104E1, participants with AML or high risk MDS with wild-type or mutant FTL3 who had not previously received a FLT3 inhibitor were randomized to receive continuous twice daily oral doses of either 50 or 100 mg midostaurin in 1 28-day cycle regimen. Participants were to be treated until disease progression or the occurrence of unacceptable treatment-related toxicity. PKC412A2104 E2 contained 2 dosing regimens: 1) intra-participant midostaurin dose escalation and 2) midostaurin with itraconazole in participants with AML and high risk MDS irrespective of FLT3 status. Eligible participants were alternately assigned to the regimens. At the Investigator's discretion, intra-participant dose escalation was allowed for any previously enrolled CPKC412A2104E1 participant receiving midostaurin at the time of the approval of amendment 4. Participants were treated until the time of disease progression.
NCT00045942 ↗	PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinas	Completed	University of California, Los Angeles	Phase 1/Phase 2	2002-01-30	CPKC412A2104 core had a 2 stage design. In stage 1, eight participants were treated. If at least one participant showed a clinical response, four more participants were recruited to stage 2. The trial was to be stopped if no participants showed a response in stage 1. POC was achieved if at least 2 participants out of 12 responded. In PKC412A2104E1, participants with AML or high risk MDS with wild-type or mutant FTL3 who had not previously received a FLT3 inhibitor were randomized to receive continuous twice daily oral doses of either 50 or 100 mg midostaurin in 1 28-day cycle regimen. Participants were to be treated until disease progression or the occurrence of unacceptable treatment-related toxicity. PKC412A2104 E2 contained 2 dosing regimens: 1) intra-participant midostaurin dose escalation and 2) midostaurin with itraconazole in participants with AML and high risk MDS irrespective of FLT3 status. Eligible participants were alternately assigned to the regimens. At the Investigator's discretion, intra-participant dose escalation was allowed for any previously enrolled CPKC412A2104E1 participant receiving midostaurin at the time of the approval of amendment 4. Participants were treated until the time of disease progression.
NCT00045942 ↗	PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinas	Completed	Weill Medical College of Cornell University	Phase 1/Phase 2	2002-01-30	CPKC412A2104 core had a 2 stage design. In stage 1, eight participants were treated. If at least one participant showed a clinical response, four more participants were recruited to stage 2. The trial was to be stopped if no participants showed a response in stage 1. POC was achieved if at least 2 participants out of 12 responded. In PKC412A2104E1, participants with AML or high risk MDS with wild-type or mutant FTL3 who had not previously received a FLT3 inhibitor were randomized to receive continuous twice daily oral doses of either 50 or 100 mg midostaurin in 1 28-day cycle regimen. Participants were to be treated until disease progression or the occurrence of unacceptable treatment-related toxicity. PKC412A2104 E2 contained 2 dosing regimens: 1) intra-participant midostaurin dose escalation and 2) midostaurin with itraconazole in participants with AML and high risk MDS irrespective of FLT3 status. Eligible participants were alternately assigned to the regimens. At the Investigator's discretion, intra-participant dose escalation was allowed for any previously enrolled CPKC412A2104E1 participant receiving midostaurin at the time of the approval of amendment 4. Participants were treated until the time of disease progression.

Clinical Trial Conditions for MIDOSTAURIN

Condition Name

Condition Name for MIDOSTAURIN
Intervention	Trials
Acute Myeloid Leukemia	21
Leukemia	5
Myelodysplastic Syndrome	5
Untreated Adult Acute Myeloid Leukemia	4

Condition MeSH

Condition MeSH for MIDOSTAURIN
Intervention	Trials
Leukemia, Myeloid, Acute	39
Leukemia	35
Leukemia, Myeloid	34
Myelodysplastic Syndromes	11

Clinical Trial Locations for MIDOSTAURIN

Trials by Country

Trials by Country for MIDOSTAURIN
Location	Trials
United States	220
Italy	58
Japan	33
Germany	18
Spain	13

Trials by US State

Trials by US State for MIDOSTAURIN
Location	Trials
Massachusetts	16
California	14
Florida	9
Texas	9
Michigan	9

Clinical Trial Progress for MIDOSTAURIN

Clinical Trial Phase

Clinical Trial Phase for MIDOSTAURIN
Clinical Trial Phase	Trials
PHASE1	2
Phase 3	6
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for MIDOSTAURIN
Clinical Trial Phase	Trials
Completed	17
Recruiting	15
Active, not recruiting	6

Clinical Trial Sponsors for MIDOSTAURIN

Sponsor Name

Sponsor Name for MIDOSTAURIN
Sponsor	Trials
Novartis Pharmaceuticals	21
National Cancer Institute (NCI)	8
Novartis	4

Sponsor Type

Sponsor Type for MIDOSTAURIN
Sponsor	Trials
Other	50
Industry	35
NIH	8

MIDOSTAURIN Clinical Trials Update, Market Analysis, and Patent-Linked Launch Projections

Last updated: May 22, 2026

Midostaurin (Rydapt) is an oral multitargeted kinase inhibitor used in systemic mastocytosis and, in combination with standard chemotherapy, for FLT3-mutated acute myeloid leukemia (AML) and advanced aggressive systemic mastocytosis (ASM), among other indications. The market outlook is dominated by (1) FLT3-mutant AML treatment penetration and regimen selection, (2) durability of use in advanced systemic mastocytosis, and (3) competitive erosion risk from newer FLT3 inhibitors, especially when payers shift to agents with clearer sequencing or tolerability profiles.

MIDOSTAURIN clinical trials update: what studies drive efficacy and next-line expansion?

Snapshot: Midostaurin’s active clinical profile is anchored around FLT3-mutated AML and advanced systemic mastocytosis. Most high-signal evidence remains based on historical pivotal datasets; the incremental clinical-trial value going forward is in sequencing, combination positioning, and biomarker-defined subgroups rather than brand-new monotherapy survival claims.

Which midostaurin trials matter by program area (FLT3 AML vs mastocytosis)?

FLT3-mutated AML

• Core evidence: Phase 3 trial supporting midostaurin with induction and consolidation chemotherapy in FLT3-mutated AML (standard-of-care incorporation in the label).
• Current “update” emphasis: Trials and post-marketing studies focused on real-world regimen adoption, dose intensity feasibility, and subgroup outcomes by mutation type (e.g., ITD vs TKD), MRD dynamics, and consolidation partner selection.

Advanced systemic mastocytosis (AdvSM)

• Core evidence: Phase 2 dataset informing treatment of ASM, aggressive systemic mastocytosis with associated hematologic neoplasm, and mast cell leukemia (MCL).
• Current “update” emphasis: Studies that quantify long-term control of organ involvement, pain/symptom endpoints, mediator-related outcomes, and safety with continued exposure.

What endpoints are currently most relevant to label-relevant positioning?

• FLT3 AML: event-free survival (EFS), overall survival (OS) where available, complete remission rates, MRD, and relapse patterns stratified by FLT3 mutation class.
• AdvSM: response rate with symptom and organ-function measures, time to response, duration of response, and toxicity profile under longer exposure.

What is the practical impact of “clinical trials update” on market uptake?

• In AML, uptake depends less on incremental phase 1/2 signals and more on whether midostaurin remains a preferred FLT3 backbone in specific chemo-combination pathways and hospital formularies.
• In mastocytosis, uptake depends on long-term tolerability, clinician familiarity, and whether competing agents displace midostaurin in systemic neoplasms where alternative kinase inhibition options exist.

MIDOSTAURIN market analysis: where is revenue most likely to concentrate and why?

Snapshot: Revenue concentration is expected to remain split between hematologic oncology (FLT3 AML combination use) and hematology/immunology (advanced systemic mastocytosis). The strongest demand lever is FLT3-mutant AML incidence and adoption of FLT3-directed induction/consolidation strategy.

Market demand drivers

1. FLT3-mutant AML pool size: Treated via chemo plus a targeted FLT3 agent at diagnosis. Adoption increases with rapid FLT3 testing and guideline-concordant regimen selection.
2. Institutional formulary behavior: Midostaurin’s differentiation versus newer FLT3 inhibitors hinges on local standard protocols, bundled chemo pathways, and payer policies.
3. AdvSM treatable population: Chronic relapsing AdvSM (including ASM, SM-AHN, and MCL) creates sustained usage patterns; payer and patient-access constraints determine net revenue more than trial-driven bursts.

Key usage constraints

• Combination regimens: In AML, midostaurin is positioned with induction and consolidation chemo. If centers shift to alternative FLT3 agents with different administration schedules or perceived tolerability advantages, midostaurin’s share can erode.
• Treatment duration and adverse event management: Gastrointestinal effects, cytopenias overlap with chemo, and monitoring burden influence switching behavior.

Competitive pressure framework for MIDOSTAURIN

• Direct category rivals: Newer FLT3 inhibitors with convenience, potency, and different PK/PD profiles have created substitution pressure in FLT3 AML. The practical question for midostaurin is not whether it works, but whether clinicians prefer it as the FLT3 backbone when treatment pathways permit switching.
• AdvSM alternatives: Other kinase inhibitors and targeted approaches for mast cell disease can compete where efficacy, tolerability, and long-term responses are perceived to be stronger.

How strong is the competitive moat for MIDOSTAURIN: what advantages persist vs newer FLT3 inhibitors?

Snapshot: Midostaurin’s moat comes from label breadth across mast cell neoplasms and integration into chemo-based FLT3 AML regimens. The weakening force is substitution to newer FLT3-directed agents when outcomes are similar and dosing or tolerability is favored.

Where midostaurin retains structural advantages

• Established chemo-combination workflow in FLT3 AML: Hospitals with midostaurin protocols show higher inertia and lower switching.
• AdvSM clinical familiarity: Clinician comfort with long-term use and predictable safety monitoring reduces adoption friction.

Where midostaurin is most exposed

• FLT3 AML switching risk: When newer FLT3 inhibitors become default choices, midostaurin share declines unless evidence or payer policy preserves it as a preferred option.

MIDOSTAURIN exclusivity and patent timeline: when does market protection expire and generic entry risk rise?

Snapshot: A complete, precise exclusivity and patent expiration projection requires Orange Book and patent family mapping by formulation and method-of-use claims. Without that dataset in the prompt context, only the structural risk framing can be provided: generic entry risk increases when (1) primary drug product patents expire, (2) any remaining pediatric exclusivity or additional regulatory exclusivities end, and (3) any unexpired method-of-use claims are narrowed or extinguished via litigation or licensing.

Launch-protection levers that typically matter for midostaurin

• Composition of matter patents (highest value, earliest expiration for generics)
• Formulation patents (delays generics via non-infringing carve-outs)
• Method-of-use patents (risk can be higher if generics seek label carve-outs for FLT3 AML vs AdvSM)
• Regulatory exclusivities (5-year new chemical entity or other scheme depending on approval pathway history; later extensions depend on supplemental applications)

Paragraph IV and litigation risk

Generic entry typically follows one of two patterns:

• Full-label generic after composition patent expiration and Orange Book clearing.
• Carve-out strategy where generics launch only for non-protected indications or only for protected-dose forms, if method-of-use claims block the broader label.

What is the Orange Book status of MIDOSTAURIN and how does it affect generic entry scenarios?

Snapshot: The Orange Book status is a gating variable for timing. Market projection depends on whether generic applicants can launch without triggering infringement in any listed patents for the relevant label indications (FLT3 AML combination use vs AdvSM). With no Orange Book listing data provided, a precise status table cannot be generated.

MIDOSTAURIN patent estate: how many patents cover the drug and what claim types are the biggest barriers?

Snapshot: Midostaurin’s patent estate historically includes multiple layers: drug substance, drug product/formulation, and use claims for oncology indications. The biggest generic barriers typically arise from:

• Composition of matter (most decisive)
• Formulation/processing (manufacturing-specific)
• Method-of-use that ties dosing regimen to FLT3-mutated AML or AdvSM disease states

A quantified “how many patents” breakdown requires a family-level patent map by jurisdiction and Orange Book claim coverage.

MIDOSTAURIN clinical-to-commercial projection: what will revenue do over the next 3-5 years?

Snapshot: A reasonable directional projection is:

• Base demand: continues through ongoing diagnosis and maintenance therapy in AdvSM and continued use in FLT3 AML.
• Share pressure: increases over time if newer FLT3 inhibitors and alternative regimens capture additional addressable share.
• Net effect by segment: AML is more substitutable and payer-driven; AdvSM is more persistent but may still face substitution if competing agents show stronger long-duration disease control.

Three scenario framework (directional, market-logic-based)

1. Base case (moderate share erosion):
   • AML share declines slowly as newer FLT3 agents gain default status.
   • AdvSM remains more stable, with gradual conversion from midostaurin to alternatives depending on perceptions and access.
2. Bull case (label endurance and formulary retention):
   • Midostaurin retains protocol status in more centers due to demonstrated tolerability management and payer stability.
   • AML adoption continues as FLT3 testing penetration increases.
3. Bear case (accelerated substitution):
   • Rapid guideline or payer shifts to newer FLT3 inhibitors reduce midostaurin’s chemo-combination share.
   • AdvSM substitution increases if alternatives demonstrate superior symptom-organ response durability.

MIDOSTAURIN biosimilar risk: does it face biologics-style competition?

Snapshot: Midostaurin is a small molecule; there is no biosimilar pathway. Competitive risk is exclusively generic and “me-too” small molecules in FLT3 and mast cell targeting.

What generic entry risks exist for MIDOSTAURIN and when would payers respond?

Snapshot: Generic entry risk timing is driven by patent and exclusivity expirations tied to the relevant dosage form and label scope. Payer response usually follows:

• Initial discounting upon first generic launch,
• Faster switching in AML once any protected indication carve-outs are cleared,
• Slower substitution in AdvSM when prescribers remain conservative and safety monitoring familiarity matters.

A precise “when” and “risk magnitude” projection requires Orange Book patent expiry dates and any Paragraph IV filings tied to the listed patents.

MIDOSTAURIN vs alternative FLT3 inhibitors: how do efficacy and regimen fit drive market share?

Snapshot: Midostaurin competes as a chemo-combination FLT3 backbone in AML and as a multi-indication agent in mast cell disease. Market share depends on regimen fit: where a newer FLT3 inhibitor replaces midostaurin, share falls regardless of midostaurin’s absolute efficacy.

What payer and physician selection criteria typically decide between FLT3 inhibitors?

• Dosing and administration simplicity
• Drug-drug interaction profile with chemo regimens
• Safety and tolerability, especially in cytopenic patients
• Reimbursement and access constraints

MIDOSTAURIN regulatory status and label scope: which indications anchor demand?

Snapshot: The drug’s label scope across FLT3-mutated AML (combination use) and advanced systemic mastocytosis supports demand stability versus single-indication products. Any future indication expansion would depend on clinical trial endpoints translating into regulatory acceptance.

MIDOSTAURIN manufacturing and formulation IP barriers: what could block generic supply?

Snapshot: For small molecules like midostaurin, supply barriers are usually IP-based (formulation/process) rather than specialized manufacturing exclusivity. If formulation patents persist, generic applicants face slower development or require non-infringing process changes.

What patent litigation affects MIDOSTAURIN market trajectory?

Snapshot: Litigation timing affects launch schedules via stays or settlement agreements. Market trajectory shifts most when:

• A settlement accelerates generic launch,
• Court outcomes narrow method-of-use claims or preserve them across indications.

A precise litigation timeline requires case numbers, dates, and settlement terms.

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Key Takeaways

• Midostaurin demand is anchored by two clinical pillars: FLT3-mutated AML combination therapy and advanced systemic mastocytosis.
• Market risk is primarily substitution pressure from newer FLT3 inhibitors in AML rather than biologics-style competition.
• Revenue durability is stronger in AdvSM due to longer-term treatment patterns and prescribing inertia.
• Generic entry timing hinges on Orange Book-listed patent expirations and any litigation outcomes tied to those listed patents; this determines whether generics can launch full-label or only carve-out.
• A forward projection is best expressed in directional scenarios: base case expects gradual share erosion in AML with more stable AdvSM demand.

FAQs

1. Does midostaurin require FLT3 confirmation testing before prescribing in AML, and how does that affect uptake?
2. Which advanced systemic mastocytosis subtypes (ASM, SM-AHN, MCL) drive the highest midostaurin persistence and spend concentration?
3. How do dosing schedule and adverse event monitoring requirements influence formulary adoption versus newer FLT3 inhibitors?
4. What generic launch strategy is most likely for midostaurin: full-label versus indication carve-out, and what patent types would block each path?
5. How do payer policies on first-line AML targeted therapy selection change midostaurin’s addressable share?

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References

1. FDA. Drug approvals and label information for midostaurin (Rydapt). U.S. Food and Drug Administration. (Access via Drugs@FDA).
2. EMA. Rydapt (midostaurin) product information and EPAR. European Medicines Agency. (Access via EMA).
3. NCBI/PMC. Clinical study publications for midostaurin in FLT3-mutated AML and advanced systemic mastocytosis. National Center for Biotechnology Information.

(No additional sources are cited because patent-expiration dates, Orange Book entries, and specific trial-by-trial “current update” listings were not provided in the prompt context.)