CurrentHealth NetPolicy CP PHAR.454

Avapritinib (Ayvakit) coverage

Defines medical necessity and prior authorization criteria for avapritinib (Ayvakit) for commercial, HIM, and Medicaid lines of business, including FDA-approved and selected off-label indications and renewal criteria.

Policy Summary

PayerHealth Net

PolicyAvapritinib (Ayvakit) coverage

Policy CodePolicy CP PHAR.454

Change TypeNo material change

Effective DateMar 1, 2020

Next Review DateN/A

Key ActionPrior authorization required; submit documentation (chart notes, labs) showing member meets indication-specific criteria and dosing limits.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3FDA-approved indications listed

6-12 moapproval durations

>=50kplatelet minimum

300 mgmax GIST dose

Coverage and Medical Necessity Criteria

Initial Therapy — GIST

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GIST initial criteria: 1. Diagnosis of unresectable, recurrent, progressive, or metastatic gastrointestinal stromal tumor (GIST). 2. Prescribed by or in consultation with an oncologist. 3. Age ≥ 18 years. 4. For brand Ayvakit requests, member must use generic avapritinib if available unless contraindicated or clinically significant adverse effects are experienced. 5. Prescribed as single-agent therapy. 6. Dose does not exceed 300 mg per day and 1 tablet per day unless the dose is supported by practice guidelines or peer-reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). 7. Documentation of a PDGFRA exon 18 mutation (including D842V or other exon 18 mutations) as applicable. 8. One of the following: (a) Failure of imatinib unless contraindicated or clinically significant adverse effects are experienced; or (b) Request is for treatment in a state with regulations against step therapy in certain oncology settings (see Appendix D).

Initial Therapy — Advanced Systemic Mastocytosis (AdvSM)

Initial approval for Advanced Systemic Mastocytosis (AdvSM) when ALL of the following are met:

AdvSM initial criteria: 1. Diagnosis of advanced systemic mastocytosis (ASM), systemic mastocytosis with associated hematologic neoplasm (SM‑AHN), or mast cell leukemia (MCL). 2. Age ≥ 18 years. 3. Prescribed by or in consultation with an oncologist, allergist, or immunologist. 4. Prescribed as single‑agent therapy. 5. Documentation of platelet count ≥ 50 x 10^9/L (≥ 50,000/mcL). 6. For brand Ayvakit requests, member must use generic avapritinib if available unless contraindicated or clinically significant adverse effects are experienced. 7. Dose: 200 mg per day (1 tablet per day) unless a different dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).

Initial Therapy — Indolent Systemic Mastocytosis (ISM)

Initial approval for Indolent Systemic Mastocytosis (ISM) when ALL of the following are met:

ISM initial criteria: 1. Diagnosis of indolent systemic mastocytosis (ISM). 2. Age ≥ 18 years. 3. Prescribed by or in consultation with an oncologist, allergist, or immunologist. 4. Prescribed as single‑agent therapy. 5. Documentation of platelet count ≥ 50 x 10^9/L (≥ 50,000/mcL). 6. For brand Ayvakit requests, member must use generic avapritinib if available unless contraindicated or clinically significant adverse effects are experienced. 7. Dose: 25 mg per day (1 tablet per day) unless a different dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).

Initial Therapy — MLNE with PDGFRA rearrangement (off-label)

Initial approval for Myeloid/Lymphoid Neoplasm with Eosinophilia (MLNE) with PDGFRA rearrangement (off-label) when ALL of the following are met:

MLNE initial criteria: 1. Diagnosis of myeloid/lymphoid neoplasm with eosinophilia (MLNE) and FIP1L1‑PDGFRA rearrangement. 2. Prescribed by or in consultation with a hematologist or oncologist. 3. For brand Ayvakit requests, member must use generic avapritinib if available unless contraindicated or clinically significant adverse effects are experienced. 4. Documentation of PDGFRA D842V mutation as applicable. 5. One of the following: (a) Failure of imatinib unless contraindicated or clinically significant adverse effects are experienced; or (b) Request is for treatment in a state with regulations against step therapy in certain oncology settings (see Appendix D). 6. Dose is within FDA maximum limits for any FDA‑approved indication or is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).

Continued Therapy — Continued therapy for any covered indication

Continued therapy — for any covered indication when ALL of the following are met:

Continued therapy criteria: 1. Member is currently receiving Ayvakit via the Centene benefit, or documentation supports the member has received Ayvakit for at least 30 days for a covered indication. 2. Member is responding positively to therapy. 3. If request is for a dose increase, the new dose does not exceed the indication‑specific maximums (GIST: 300 mg/day; AdvSM: 200 mg/day; ISM: 25 mg/day) unless the new dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). 4. For brand Ayvakit requests, member must use generic avapritinib if available unless contraindicated or clinically significant adverse effects are experienced.

Initial Therapy — Diagnosis-Specific Criteria

Initial Therapy — Grouped initial therapy criteria by indication

Grouped initial therapy criteria by indication (aggregate of indication‑specific initial therapy criteria):

Initial therapy: See individual indication nodes for required documentation and prescriber specialty. Common requirements across indications include: age ≥ 18 years; prescriber specialty appropriate to the diagnosis (oncologist, hematologist, allergist, or immunologist as specified); single‑agent use; use generic avapritinib when available for brand requests unless contraindicated; documentation of relevant PDGFRA mutation where applicable; platelet count ≥ 50 x 10^9/L for systemic mastocytosis indications; dosing limits by indication (GIST 300 mg/day; AdvSM 200 mg/day; ISM 25 mg/day); and, where applicable, failure of imatinib unless contraindicated or state regulations prohibit step therapy.

Criteria for Continued Therapy

Continued Therapy — Criteria for continued therapy (renewal) across indications

Criteria for continued therapy (renewal) across indications:

Continued therapy: 1. Member currently receiving Ayvakit via Centene or has documentation of receiving Ayvakit for ≥ 30 days for a covered indication. 2. Member is demonstrating a positive clinical response to therapy. 3. Dose remains within indication‑specific maximums (GIST 300 mg/day; AdvSM 200 mg/day; ISM 25 mg/day) unless the higher dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). 4. For brand Ayvakit requests, member must use generic avapritinib if available unless contraindicated or clinically significant adverse effects are experienced.

Prior Authorization, Documentation, and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for avapritinib (Ayvakit). Requests must meet the listed diagnosis-specific criteria and dosing limits. For Commercial lines of business, approval duration is 12 months or the duration of request, whichever is less. State-level regulations may prohibit step therapy or redirection in certain oncology settings; when such prohibitions apply (see Appendix D), requirements for prior failure of imatinib or other step therapy redirections do not apply (oncology bypass).

Commercial approval duration: 12 months or duration of request, whichever is less
Oncology bypass: state prohibitions on redirection/step therapy for advanced/metastatic cancer override step requirements — see Appendix D
Provider must submit supporting documentation (office chart notes, lab results, or other clinical information) with the prior authorization request

Documentation Required

Documentation Required / Triggers for Denial

Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria. Documentation must include any evidence required by the diagnosis-specific criteria (for example, molecular testing results such as PDGFRA exon 18 mutation status when applicable). Lack of sufficient documentation to demonstrate that approval criteria are met, or requests for non-listed/non–FDA-approved indications without adequate evidence per off-label use policies, may result in denial.

Include laboratory results, imaging, pathology, and provider notes as applicable
Include molecular testing reports (e.g., PDGFRA exon 18 mutation) when required by indication
For off‑label uses, include peer‑reviewed literature or guideline support per off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53)

Step Therapy

Step Therapy and State Exceptions

Step therapy requirements (for example, documentation of failure of imatinib prior to avapritinib) apply where specified in the indication criteria unless contraindicated or clinically significant adverse effects are documented. However, states listed in Appendix D that prohibit step therapy/redirection for stage 3/4 or advanced/metastatic cancer (see Appendix D) preclude enforcement of these redirection/step therapy requirements — including an oncology bypass added in 1Q 2025. Providers should indicate on the request if the patient’s treatment is for a cancer diagnosis and the member resides in or the request is governed by one of the states in Appendix D so that redirection/step therapy requirements are not applied improperly.

When indication requires failure of imatinib, documentation of intolerance or contraindication is acceptable in lieu of failure
If the request is for treatment in a state listed in Appendix D that prohibits redirection for the specific oncology setting, step therapy/redirection should not be applied (oncology bypass)
Appendix D lists states and the applicable cancer stage/settings where step therapy/redirection prohibitions apply

Step Therapy Rules and State Exceptions

Indication	Step therapy requirement	Notes / state exceptions
Gastrointestinal stromal tumor (GIST) — unresectable, recurrent, progressive, or metastatic	Failure of imatinib is required unless contraindicated or clinically significant adverse effects are experienced	If the request is for treatment associated with cancer in a state with regulations against step therapy (see Appendix D), the imatinib requirement may be waived
Myeloid/lymphoid neoplasm with eosinophilia and FIP1L1‑PDGFRA rearrangement (MLNE) — off‑label	Failure of imatinib is required unless contraindicated or clinically significant adverse effects are experienced	State regulations prohibiting step therapy for advanced/metastatic cancer may override the imatinib requirement (see Appendix D)

Topic	Policy statement	Details / effective updates
State prohibitions on step therapy/redirection	Step therapy or redirection is prohibited in specified states for stage 4 (and in some states stage 3) metastatic/advanced cancer and associated conditions	States listed in Appendix D include FL, GA, IA, LA, MS, NV, OH, OK, PA, TN, TX; specific applicability and notes per state are listed in Appendix D
Oncology bypass language (1Q2025)	An oncology bypass was added to existing redirection provisions to reflect updated prior authorization/redirection handling for oncology requests	1Q 2025 annual review: added oncology bypass language to existing redirections (P&T approval 02.25); see policy history for effective date

Clinical Thresholds and Product Information

Platelet count — minimum required for systemic mastocytosis

Minimum platelet countDocumentation of platelet count >= 50 x 10^9/L (>= 50,000/mcL) is required

Applicable indicationsRequired for Advanced Systemic Mastocytosis (ASM, SM-AHN, MCL) initial and continued therapy criteria

Source guidanceRequirement added per NCCN Compendium and prescribing information (1Q 2022 annual review)

Platelet count — alternate reference for platelet requirement

Indication contextRequired for Indolent Systemic Mastocytosis (ISM) initial and continued therapy criteria

Documentation noteAdded to policy based on NCCN Compendia and prescribing information (1Q 2022)

Product strengths and dosing — Available tablet strengths and indication-specific maximum doses

Available tablet strengthsTablets: 25 mg, 50 mg, 100 mg, 200 mg, and 300 mg

GIST dosing (maximum)Up to 300 mg/day (1 tablet/day)

Advanced systemic mastocytosis dosing (maximum)200 mg/day (1 tablet/day)

Indolent systemic mastocytosis dosing (maximum)25 mg/day (1 tablet/day)

Drug Background and Indications

Avapritinib (Ayvakit) is an oral tyrosine kinase inhibitor approved for treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation (including PDGFRA D842V) and for systemic mastocytosis subtypes including advanced systemic mastocytosis (AdvSM; ASM, SM‑AHN, MCL) and indolent systemic mastocytosis (ISM). The product is available as tablets in 25 mg, 50 mg, 100 mg, 200 mg, and 300 mg strengths with indication‑specific dosing (e.g., GIST maximum 300 mg/day; AdvSM typical dose 200 mg/day; ISM typical dose 25 mg/day).

Definitions and Product Details

advanced systemic mastocytosis — definition

TermAdvanced systemic mastocytosis (AdvSM)

IncludesAggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL)

Clinical noteTreatment criteria require prescriber specialty (oncologist, allergist, or immunologist), single-agent use, and platelet documentation >= 50 x 10^9/L

indolent systemic mastocytosis — definition

TermIndolent systemic mastocytosis (ISM)

Clinical requirementPrescribed by or in consultation with an oncologist, allergist, or immunologist; single-agent therapy; documentation of platelet count >= 50 x 10^9/L

DosingTypical approved dose per policy: 25 mg once daily

Product strengths and dosing — tablet strengths and dosing overview

Available tablet strengths25 mg, 50 mg, 100 mg, 200 mg, 300 mg tablets

Indication-specific maximum dosesGIST: 300 mg/day; Advanced systemic mastocytosis: 200 mg/day; Indolent systemic mastocytosis: 25 mg/day

AdministrationOral tablets, 1 tablet per day at specified dose unless supported by guidelines or literature