UnitedHealthcare Ayvakit Prior Auth Coverage Update

Coverage Criteria and Indications

Pediatric (under 19) initial authorization

Automatic approval for patients under 19 years of age

Patients <19: Patient is less than 19 years of age

Authorization will be issued for 12 months

GIST Initial Authorization

Gastrointestinal stromal tumor (GIST) — Initial authorization

GIST initial: Diagnosis of gastrointestinal stromal tumor (GIST)

GIST disease state: One of: patient has unresectable, recurrent, or metastatic disease after failure on approved therapies (e.g., imatinib, sunitinib, regorafenib, ripretinib); OR disease is resectable with significant morbidity; OR unresectable; OR metastatic; OR recurrent; OR limited progression; OR residual disease with significant morbidity; OR gross residual disease (R2 resection)

GIST mutation: Presence of a PDGFRA exon 18 mutation, including D842V

Authorization will be issued for 12 months

GIST Reauthorization

GIST reauthorization

GIST reauth: Patient does not show evidence of progressive disease while on Ayvakit therapy

Authorization will be issued for 12 months

Myeloid/Lymphoid Neoplasms Initial Authorization

Myeloid/lymphoid neoplasms with eosinophilia — Initial authorization

Myeloid/lymphoid initial: Diagnosis of myeloid/lymphoid neoplasms with eosinophilia

Genetics: Presence of a FIP1L1-PDGFRA rearrangement AND presence of a PDGFRA D842V mutation

Authorization will be issued for 12 months

Myeloid/Lymphoid Reauthorization

Myeloid/lymphoid neoplasms — Reauthorization

Myeloid/lymphoid reauth: Patient does not show evidence of progressive disease while on Ayvakit therapy

Authorization will be issued for 12 months

Systemic Mastocytosis Initial Authorization

Systemic mastocytosis — Initial authorization

SM diagnoses: Diagnosis of one of: advanced systemic mastocytosis; aggressive systemic mastocytosis; systemic mastocytosis with an associated hematologic neoplasm; mast cell leukemia; indolent systemic mastocytosis

SM platelets: Platelet count is greater than or equal to 50 x 10^9/L>= 50 x 10^9/L

Authorization will be issued for 12 months

Systemic Mastocytosis Reauthorization

Systemic mastocytosis — Reauthorization

SM reauth: Patient does not show evidence of progressive disease while on Ayvakit therapy

Authorization will be issued for 12 months

Ayvakit (avapritinib) is not recommended for treatment of patients with advanced systemic mastocytosis (AdvSM) or indolent systemic mastocytosis (ISM) who have a platelet count less than 50 x 10^9/L. This limitation aligns with the product labeling and the policy's systemic mastocytosis eligibility criteria, which require a minimum platelet threshold for coverage authorization.

Requests for Ayvakit that do not meet the specific diagnosed indications or required molecular markers are considered not medically necessary under this policy. Specifically, use of Ayvakit outside the listed diagnoses (GIST with PDGFRA exon 18 mutation including D842V; myeloid/lymphoid neoplasms with FIP1L1‑PDGFRA rearrangement plus PDGFRA D842V; and specified systemic mastocytosis subtypes) or in the absence of the required molecular testing will not meet criteria. For GIST, initiation of Ayvakit prior to documented failure on approved therapies (examples: imatinib, sunitinib, regorafenib, ripretinib) is not consistent with the step‑therapy requirement unless an NCCN‑allowed context applies.

Initial Therapy — Indication-Specific Requirements

Initial therapy

Initial authorization criteria by indication

GIST initial: Diagnosis of GIST AND presence of PDGFRA exon 18 mutation (including D842V) AND disease context per policy (e.g., unresectable/recurrent/metastatic after failure on approved therapies or other NCCN-allowed contexts)

Authorization for 12 months

Myeloid/lymphoid initial: Diagnosis of myeloid/lymphoid neoplasms with eosinophilia AND presence of FIP1L1-PDGFRA rearrangement AND PDGFRA D842V mutation

Authorization for 12 months

SM initial: Diagnosis of specified systemic mastocytosis subtype AND platelet count >= 50 x 10^9/L>= 50 x 10^9/L

Authorization for 12 months

Reauthorization and Continuation Rules

Reauthorization / Continuation

Reauthorization rules across indications

Continuation: Patient does not show evidence of progressive disease while on Ayvakit therapy

Authorization will be issued for 12 months

Provider Actions, Documentation, and Denial Triggers

Prior Authorization

Prior Authorization Required

Prior authorization/notification is required for Ayvakit (avapritinib) per UnitedHealthcare Pharmacy Clinical Pharmacy Programs. Requests for members under age 19 will automatically process without coverage review. State mandates for off‑label coverage or alternate compendia may supersede these criteria where applicable.

Program: Prior Authorization/Notification
Medication: Ayvakit (avapritinib)
Authorization duration: 12 months for approved indications

Documentation Required

GIST — Prior Lines / Clinical Context

For GIST, Ayvakit may be approved when the patient has a diagnosis of gastrointestinal stromal tumor (GIST) and meets one of the following clinical contexts: unresectable, recurrent, or metastatic disease after failure of approved therapies (examples include imatinib, sunitinib, regorafenib, ripretinib); OR disease that is resectable only with significant morbidity; limited progression; residual or gross residual disease (including R2 resection). In addition, documentation must show presence of a PDGFRA exon 18 mutation (including D842V).

Key Clinical Thresholds and Coding Notes

inv-10: Platelet count — minimum platelet count required for systemic mastocytosis eligibility

Minimum platelet thresholdPlatelet count >= 50 x 10^9/L for systemic mastocytosis eligibility

ApplicabilityApplies to advanced systemic mastocytosis (AdvSM), aggressive SM (ASM), SM-AHN, mast cell leukemia (MCL), and indolent systemic mastocytosis (ISM)

Authorization periodAuthorization will be issued for 12 months when threshold met

Exclusion noteAyvakit is not recommended for treatment of AdvSM or ISM with platelet counts < 50 x 10^9/L

Step Therapy Requirements

Step	Requirement	Failure criteria / notes
1	Required for GIST unless other NCCN contexts apply; patient must have a diagnosis of gastrointestinal stromal tumor (GIST).	Patient has unresectable, recurrent, or metastatic disease after failure on approved therapies (examples: imatinib, sunitinib, regorafenib, ripretinib) OR meets other listed disease contexts (resectable with significant morbidity; unresectable; metastatic; recurrent; limited progression; residual disease with significant morbidity; gross residual disease [R2 resection]).

Definitions and Molecular Markers

inv-16: PDGFRA exon 18 D842V — definition and relevance to GIST sensitivity to avapritinib

DefinitionPDGFRA exon 18 D842V — an activating mutation in PDGFRA exon 18 (D842V) associated with GIST

Predictive relevancePresence of PDGFRA exon 18 mutation, including D842V, predicts sensitivity to avapritinib for GIST

Indication linkagePolicy requires documented PDGFRA exon 18 mutation (including D842V) for GIST initial authorization

Authorization periodAuthorization will be issued for 12 months when mutation is present

inv-17: FIP1L1-PDGFRA rearrangement — definition and relevance to myeloid/lymphoid neoplasms with eosinophilia

DefinitionFIP1L1-PDGFRA rearrangement — a genetic fusion (FIP1L1-PDGFRA) associated with myeloid/lymphoid neoplasms with eosinophilia

Background

Avapritinib (Ayvakit) is a kinase inhibitor indicated for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including D842V, and for treatment of advanced systemic mastocytosis (AdvSM) — including aggressive SM, SM‑AHN, and mast cell leukemia — as well as indolent systemic mastocytosis. For GIST, NCCN guidance also supports avapritinib for continued treatment in limited progression and for disease that is unresectable, recurrent, metastatic, gross residual (R2 resection), or resectable disease with significant morbidity when other therapies are ineffective. The policy issues prior authorization for covered indications with authorizations generally granted for 12 months when criteria are met.

Revision History

2025-10-01policy effective dateLatest

Policy effective date set to 2025-10-01 (Program Effective Date).

2025-07-01annual review

Annual review in July 2025 updated wording of systemic mastocytosis criteria per NCCN without change to clinical intent and updated references.

2024-07annual review

OpenPayer

Avapritinib (Ayvakit) prior authorization

Coverage Criteria and Indications

Initial Therapy — Indication-Specific Requirements

Reauthorization and Continuation Rules

Provider Actions, Documentation, and Denial Triggers

Key Clinical Thresholds and Coding Notes

Step Therapy Requirements

Definitions and Molecular Markers

Background

Revision History