ModifiedPremera BluecrossPolicy N/A

Phosphoinositide 3-kinase (PI3K) Inhibitors Coverage Criteria

Defines medical necessity, authorization durations, documentation, benefit routing, and coding for PI3K inhibitor drugs for specified oncologic and genetic indications; applies to Premera Bluecross members and their providers.

Policy Summary

PayerPremera Bluecross

PolicyPhosphoinositide 3-kinase (PI3K) Inhibitors Coverage Criteria

Policy CodePolicy N/A

Change TypeCoverage additions and removals (agent-level updates)

Effective DateMar 1, 2025

Next Review DateN/A

Key ActionSubmit office visit notes documenting diagnosis, history, exam, and medication history and include tumor genomic testing (PIK3CA or relevant alterations) when requesting authorization.

SourceLink

POLICY UPDATE CHANGES

Added coverage criteria for Itovebi (inavolisib).

Added coverage criteria for Truqap (capivasertib) for treatment of certain individuals with breast cancer.

Added coverage criteria for Joenja (leniolisib) for activated PI3K delta syndrome (APDS).

Added coverage for Vijoice (alpelisib) and Piqray (alpelisib) for treatment of PROS.

Removed Copiktra (duvelisib) coverage for relapsed or refractory follicular lymphoma after voluntary withdrawal by manufacturer.

Removed Zydelig (idelalisib) coverage criteria for follicular lymphoma and small lymphocytic lymphoma when use was removed from prescribing information.

Clarified that the medications listed in this policy are subject to the product's FDA dosage and administration prescribing information.

multipleDrugs referenced

Phase 3Trials cited

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

12 monthsMax non-formulary auth

Black boxIdelalisib safety

2018-2025History timeframe

Coverage Criteria

Initial Therapy Coverage Criteria by Drug

Covered when ALL of the following are met for each listed drug:

Aliqopa (copanlisib) - relapsed follicular lymphoma: Individual is aged 18 years or older AND has had at least two prior systemic therapiesage >=18; >=2 prior systemic therapies

Aliqopa administered IV; see HCPCS J9057

Copiktra (duvelisib) - relapsed or refractory CLL or SLL: Individual is aged 18 years or older AND has had at least two prior systemic therapiesage >=18; >=2 prior systemic therapies

oral agent

Itovebi (inavolisib) - endocrine-resistant PIK3CA-mutated HR+/HER2- advanced/metastatic breast cancer: Individual is aged 18 years or older AND diagnosed with HR-positive, HER2-negative locally advanced or metastatic breast cancer with PIK3CA mutation AND has disease progression following at least one line of endocrine therapy in the metastatic setting OR recurrence on or within 12 months of completing adjuvant therapy AND will be given in combination with Ibrance (palbociclib) and fulvestrant as first-line therapy AND ECOG performance status 0–1 AND has not experienced disease progression on or following other PI3K inhibitors AND prescribed by or in consultation with an oncologistage >=18; ECOG 0-1

oral agent

Joenja (leniolisib) - activated PI3K delta syndrome (APDS): Individual is aged 12 years or older AND diagnosed with APDS AND has documented PI3K delta gene mutation (PIK3CD or PIK3R1) AND prescribed by or in consultation with an oncologist, medical geneticist, or hematologistage >=12

oral agent

Piqray (alpelisib) - HR+/HER2- PIK3CA-mutated advanced/metastatic breast cancer: Individual is aged 18 years or older AND diagnosed with HR-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer as detected by an FDA-approved test AND has experienced progression on or after an endocrine-based regimen AND will be used in combination with fulvestrantage >=18

oral agent

Piqray/Vijoice (alpelisib) - PIK3CA-Related Overgrowth Spectrum (PROS): For Piqray: individual is aged 18 years or older; for Vijoice: individual is aged 2 years or older AND diagnosed with PROS AND has at least one target lesion identified on imaging AND has documented PIK3CA gene mutation AND prescribed by or in consultation with an oncologist, geneticist, or hematologist AND dose for Piqray 250 mg orally once daily (where applicable)age >=18 (Piqray) or >=2 (Vijoice); dose 250 mg qd for Piqray

oral agent; measurable target lesion required for PROS

Truqap (capivasertib) - HR+/HER2- breast cancer with PI3K/AKT/PTEN alterations: Individual is aged 18 years or older AND diagnosed with HR-positive, HER2-negative locally advanced or metastatic breast cancer AND has one or more PIK3CA/AKT1/PTEN alterations AND disease progression following at least one line of endocrine therapy in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy AND will be used in combination with fulvestrant AND has not experienced disease progression on or following other PI3K/AKT/PTEN inhibitors AND documentation of alpelisib intolerance or specific mutations not sensitive to alpelisib when applicableage >=18; dose limit 400 mg BID x4 days followed by 3 days when dosing applied

oral agent; used in combination with fulvestrant

Zydelig (idelalisib) - relapsed CLL (in combination with rituximab): Relapsed chronic lymphocytic leukemia in combination with rituximab for individuals for whom rituximab alone would be appropriate therapy due to comorbidities AND dose is limited to 300 mg per day (taken as 150 mg twice daily); not indicated for first-line treatmentdose 300 mg/day

oral agent; boxed warnings and safety considerations per product labeling

Authorization Duration and Re-authorization

Authorization length and re-authorization rules:

Initial authorization lengths: Non-formulary exception reviews for all drugs may be approved up to 12 months; specific drugs may have shorter initial approvals (Copiktra, Itovebi, Joenja, Piqray for breast cancer, Truqap, and Zydelig up to 3 months; Aliqopa, Piqray for PROS, and Vijoice up to 6 months)varies by drug

See drug-specific sections for details

Re-authorization may be approved up to 12 months for most drugs if drug-specific coverage criteria are met and chart notes document continued positive clinical response; for PROS (Piqray/Vijoice) re-approval requires documentation of reduction in the sum of measurable target lesion volume from baselinere-approval up to 12 months

Clinical response documentation required

Policy updates and per-agent coverage stance

Policy updates specify coverage stance changes by agent and indication:

Itovebi (inavolisib) addition: Coverage criteria for Itovebi (inavolisib) were added in the 2025 Update; refer to product prescribing information and policy for indication-specific criteria.

See INAVO120 trial data for efficacy context

Truqap (capivasertib) addition: Coverage criteria for Truqap (capivasertib) for certain breast cancer populations were added in the 2024 Update; approval supported by CAPltello-291 evidence referenced in the policy history.

See policy trial citations for details

Joenja (leniolisib) addition: Coverage criteria for Joenja for APDS in patients aged 12 years and older were added in the 2023 Update based on randomized placebo-controlled data.

Prescribing information and trial data referenced in policy

Policy-level coverage changes and summary

Policy history reflects covered and removed indications over time; specific criteria details are in other sections of the full policy.

Policy changes summary: Added coverage criteria over time for alpelisib (Vijoice/Piqray) for PROS and certain breast cancer populations; added Joenja (leniolisib) for APDS; added Truqap (capivasertib) and Itovebi (inavolisib); removed Ukoniq (umbralisib) and removed some Zydelig (idelalisib) indications after label changes.

Refer to per-drug sections for detailed, current coverage criteria

All uses of drugs listed in this policy that are not explicitly described in the coverage criteria are considered investigational. Requests for indications, dosing, or populations outside the defined policy criteria may be denied on the basis that they are investigational and not medically necessary.

When an indication has been removed from a drug’s FDA prescribing information, that use is no longer covered under this policy. Examples include removal of the relapsed/refractory follicular lymphoma indication for Copiktra (duvelisib) and removal of certain follicular lymphoma or small lymphocytic lymphoma indications for Zydelig (idelalisib); coverage for those specific uses was removed consistent with the prescribing information.

Following the FDA withdrawal of approval for Ukoniq (umbralisib) due to safety concerns, Ukoniq has been removed from this policy for all previously FDA‑approved indications and is not covered.

Any request for use of drugs in this policy for indications not specified in the policy language is considered investigational and not medically necessary. Providers should submit documentation only for uses that meet the policy’s listed criteria; otherwise authorization is unlikely.

Indications that are not present in the current FDA prescribing information, or that have been voluntarily withdrawn by the manufacturer, are not covered. For example, manufacturer withdrawal of the relapsed/refractory follicular lymphoma indication for Copiktra and removal of certain idelalisib indications resulted in removal of coverage for those uses.

Unless an individual’s request meets the policy’s specified coverage criteria, uses of Aliqopa (copanlisib), Copiktra (duvelisib), or Zydelig (idelalisib) for other indications are considered investigational and are not covered. Historical policy edits and subsequent updates reflect removal of coverage for specific indications when those uses were removed from prescribing information or the drug was withdrawn.

Provider Actions and Documentation Requirements

Prior Authorization

Prior Authorization Required and Approval Lengths

Prior authorization is required for the medications listed in this policy. Initial approvals follow the drug-specific durations: non-formulary exception reviews for any drug in this policy may be approved up to 12 months. Other initial approvals may be shorter per the policy (e.g., 3 or 6 months) as indicated in the drug-specific criteria. Continuation (re-authorization) approvals may be granted up to 12 months provided drug-specific coverage criteria are met and chart notes document continued clinical benefit.

Non-formulary exception reviews: up to 12 months
Drug-specific initial approval windows may be 3 or 6 months as stated in the policy
Re-authorization: may be approved up to 12 months when criteria and clinical response documented

Documentation Required

FDA Dosing and Administration / Dosing Adherence

All medications in this policy are subject to the product’s FDA dosing and administration prescribing information. Documentation submitted should support the FDA-recommended dose and schedule. Prescribers must ensure dosing adherence to the approved labeling or include rationale and supporting documentation if a departure from FDA dosing is requested.

Initial Therapy Criteria

Initial Therapy Authorization Lengths

Initial approval durations vary by drug

Non-formulary exception reviews: May be approved up to 12 months

Copiktra, Itovebi, Joenja, Piqray (breast), Truqap, Zydelig: Initial approvals may be up to 3 months

Aliqopa, Piqray (PROS), Vijoice: Initial approvals may be up to 6 months

Evidence for initial therapy

Initial therapy evidence bases described by pivotal trials:

Continuation Therapy and Re-authorization

Continuation Therapy

Re-authorization conditions

General continuation: Re-authorization may be approved up to 12 months if drug-specific coverage criteria are met and chart notes document continued positive clinical response to therapy.

PROS and Vijoice continuation: For PROS (Piqray/Vijoice), re-authorization may be approved up to 12 months if chart notes demonstrate continued positive clinical response as documented by reduction in the sum of measurable target lesion volume from baseline.

Continuation in trials

Clinical trials describe continuing therapy until disease progression or unacceptable toxicity.

Continuation in trials: Treatment in trials such as CHRONOS-1 (copanlisib) and SOLAR-1 (alpelisib) was continued until disease progression or unacceptable toxicity.

Step Therapy and Sequencing

Drug / Indication	Step therapy requirement	Notes / Combination
Itovebi (inavolisib) — endocrine‑resistant PIK3CA‑mutated HR+/HER2‑ breast cancer	Prior endocrine therapy required (progression after ≥1 line in metastatic setting or recurrence within 12 months of completing adjuvant therapy)	Must be given in combination with palbociclib (Ibrance) and fulvestrant; ECOG 0–1; prescribed by or in consultation with an oncologist; no prior progression on other PI3K inhibitors
Piqray (alpelisib) — PIK3CA‑mutated HR+/HER2‑ advanced/metastatic breast cancer	Prior endocrine‑based regimen with documented progression required	Use in combination with fulvestrant; dose 250 mg orally once daily
Truqap (capivasertib) — HR+/HER2‑ breast cancer with PI3K/AKT/PTEN alterations	Prior endocrine therapy required (progression after ≥1 line in metastatic setting or early recurrence)	To be used in combination with fulvestrant; dose limited to 400 mg twice daily ×4 days then 3 days off; documentation of alpelisib intolerance or non‑sensitive mutations if applicable

Agent	Coverage change / restriction	Source / history note
Copiktra (duvelisib)	Coverage removed for relapsed/refractory follicular lymphoma (R/R FL) following voluntary manufacturer withdrawal of that indication	2022 Update: manufacturer did not pursue confirmatory trial; indication removed from prescribing information
Ukoniq (umbralisib)	Removed from policy for all FDA‑approved indications after FDA withdrawal due to safety concerns	History notes: FDA withdrew approval; policy removed Ukoniq from coverage (07/01/22)
Zydelig (idelalisib)	Certain follicular lymphoma and small lymphocytic lymphoma indications removed from coverage consistent with prescribing information changes; boxed warnings and safety concerns remain	Policy history: daily dose limit added (08/01/20); later removals for some indications noted in 2024/2025 updates

Historical edit	Policy effect / control	Reference (history entry)
Added daily dose limit for Zydelig (idelalisib)	Dose limit implemented: total daily dose limited to 300 mg per day (150 mg twice daily) for relapsed CLL in combination with rituximab; dosing controls enforced by prior authorization	History: 08/01/20 annual review — added daily dose limit to Zydelig
Coding update — HCPCS J9057 added	Operational impact: Aliqopa (copanlisib) billed under J9057; supports medical‑benefit routing for IV copanlisib	History: 01/01/19 coding update added HCPCS J9057
Step therapy sequencing and dosing controls referenced	Specific step sequences (prior endocrine therapy, required combination agents) and dosing limits are defined in full per‑drug criteria within the policy and enforced at prior authorization	See policy coverage criteria for per‑drug step requirements (e.g., Itovebi, Piqray, Truqap) and history entries for prior edits

Quantity Limits

inv-40: Piqray (alpelisib) — quantity limit entry

DrugPiqray (alpelisib)

Quantity / Dose Limit250 mg orally once daily

Indication (policy)PIK3CA‑mutated HR+/HER2‑ advanced or metastatic breast cancer (with fulvestrant) and PIK3CA‑related overgrowth spectrum (PROS)

Age requirementAdults (Piqray for PROS: age 18 years or older for Piqray formulation; Vijoice formulation may be used in younger patients)

Benefit routingOral PI3K inhibitors are managed under the pharmacy benefit

inv-41: Zydelig (idelalisib) — quantity limit entry

Drug

Site of Care and Benefit Routing

Billing Rule

Route determines benefit: oral = pharmacy; IV (Aliqopa) = medical

Oral PI3K inhibitors are managed under the pharmacy benefit; Aliqopa (copanlisib), which is administered by IV infusion, is managed under the medical benefit.

Manage Copiktra, Itovebi, Joenja, Piqray, Truqap, and Zydelig through pharmacy benefit.
Manage Aliqopa (IV copanlisib) through the medical benefit.

Billing Rule

Infusion scheduling: copanlisib given IV on Days 1, 8, 15 of 28‑day cycle

Copanlisib (Aliqopa) is administered as an intravenous infusion on an intermittent schedule (e.g., 60 mg IV on Days 1, 8, and 15 of a 28‑day cycle in trials); other agents covered by this policy are oral formulations and processed through pharmacy channels.

Aliqopa dosing in CHRONOS‑1: 60 mg IV (or weight‑based equivalent) on Days 1, 8, and 15 of a 28‑day cycle.

Billing and Coding

HCPCS codesHCPCS

J9057

Injection, copanlisib (Aliqopa), mg

HCPCS coding historyHCPCS

J9057	HCPCS code added effective 1/1/19 (policy history notes coding update).
J9999	HCPCS code removed (policy history notes).

Definitions and Key Terms

inv-26: PI3K isoforms — Class I PI3Ks have p110 catalytic subunits (alpha, beta, gamma, delta)

DefinitionClass I PI3Ks have a catalytic p110 subunit

Isoformsp110 alpha (p110α), p110 beta (p110β), p110 gamma (p110γ), p110 delta (p110δ)

RelevanceDifferent inhibitors target one or more p110 isoforms, influencing clinical activity and toxicity profiles

inv-27: CLL/SLL — CLL and SLL are manifestations of the same lymphocytic malignancy

DefinitionChronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same lymphocytic malignancy

Clinical distinctionCLL: majority of leukemic B‑cells circulate in the blood; SLL: disease predominantly in lymphoid tissue

Background

PI3K inhibitors act on the PI3K/AKT/mTOR signaling pathway to inhibit tumor cell growth and survival. Class I PI3Ks have p110 catalytic subunits with isoforms p110 alpha, beta, gamma, and delta; different agents vary in isoform specificity, which underlies their approved indications and safety profiles.

Revision History

2018-12-01policy_creation

New policy approved (initial policy effective November 13, 2018) establishing coverage framework for Aliqopa (copanlisib), Copiktra (duvelisib), and Zydelig (idelalisib) with investigational status for other uses.

2019-01-01coding_update

Added HCPCS code J9057 effective 01/01/2019 and removed HCPCS code J9999.

2020-08-01dosage_limit_added

Added a daily dose limit to Zydelig (idelalisib).

Policy Summary

PayerPremera Bluecross

PolicyPhosphoinositide 3-kinase (PI3K) Inhibitors Coverage Criteria

Policy CodePolicy N/A

Change TypeCoverage additions and removals (agent-level updates)

Effective DateMar 1, 2025

Next Review DateN/A

Key ActionSubmit office visit notes documenting diagnosis, history, exam, and medication history and include tumor genomic testing (PIK3CA or relevant alterations) when requesting authorization.

SourceLink

On This Page

Vijoice/Piqray (alpelisib) PROS addition:

Coverage for alpelisib formulations (Vijoice, Piqray) for PROS was added in the 2022 Update based on evidence of lesion volume reduction in affected individuals.

See EPIK-P1/real-world evidence in policy references

Idelalisib (Zydelig) removal for certain lymphomas: Zydelig coverage criteria were removed for treatment of certain follicular lymphoma and small lymphocytic lymphoma when these uses were removed from prescribing information; idelalisib retains FDA indications for relapsed CLL, relapsed SLL, and relapsed FL with safety warnings.

Policy history documents removal and safety alerts

Copiktra (duvelisib) R/R FL removal: Coverage was removed for duvelisib in relapsed/refractory follicular lymphoma after voluntary manufacturer withdrawal of that indication (2022 Update).

See 2022 history entry

Medications subject to FDA dosing and administration guidance
Documentation should support FDA-based dosing or provide clinical rationale for deviations

Denial Risk

Idelalisib Safety and Indication Restrictions

Idelalisib (Zydelig) carries important safety and indication restrictions. It is indicated only for relapsed CLL (in combination with rituximab), relapsed SLL, and relapsed FL. The FDA has issued safety communications and idelalisib carries boxed warnings for fatal and serious toxicities (hepatic injury, severe diarrhea/colitis, pneumonitis, infections, and intestinal perforation). Use outside the FDA‑indicated relapsed CLL/SLL/FL settings may pose significant safety risks and may be denied.

Zydelig indications limited to relapsed CLL (with rituximab), relapsed SLL, and relapsed FL
Black box warnings: hepatic, severe diarrhea/colitis, pneumonitis, infections, intestinal perforation
First-line use is not indicated and may be denied

Denial Risk

Removed Indications — Denial Risk

Uses removed from product labeling or prescribing information are not covered and may be denied. For example, coverage for certain Zydelig or other agent indications that were removed from prescribing information will not be supported.

Removed indications (per manufacturer or FDA) are not covered
Providers should verify current prescribing information before requesting coverage

Documentation Required

Tumor Genomic Documentation Required

When coverage is sought for tumor-directed therapies that require genomic selection, the medical record must document tumor genomic status (for example, documented PIK3CA mutation for alpelisib or other agents where indicated). Testing results, method, and date should be included with the request.

Documented PIK3CA mutation required where specified (e.g., Piqray/Itovebi)
Include test method, result, and date in submitted records
Prescriber should be an oncologist/geneticist/hematologist when indicated

Prior Authorization

Combination and Prior Therapy Requirements

Some agents must be given in combination with specified therapies or after certain prior therapies per the coverage criteria. For example, Itovebi (inavolisib) is covered when given in combination with palbociclib (Ibrance) and fulvestrant, and other drugs require prior lines of systemic therapy or demonstration of intolerance to alternative agents before approval.

Itovebi must be used in combination with palbociclib (Ibrance) and fulvestrant for the approved indication
Many agents require prior systemic therapies (e.g., ≥1 or ≥2 prior lines as specified)
Document prior therapies, dates, and reasons for discontinuation or intolerance

Step Therapy

Step Edits Aligned to Indications and Guidelines

Step edits and coverage align with current FDA prescribing information and guideline updates (NCCN and other referenced guidance). Providers should expect coverage decisions and step requirements to reflect the most recent prescribing information and guideline-reviewed indications.

Coverage aligned to FDA labeling and NCCN guideline updates
Step-edit or prior‑therapy requirements may change as indications are updated

Documentation Required

Required Clinical Documentation

Submit office visit notes that document diagnosis, relevant history, physical exam, medication history, and other supporting documentation (imaging, laboratory/genomic test results) to demonstrate that medical necessity criteria are met.

Office visit notes with diagnosis, history, physical evaluation, and medication history
Include imaging reports and genomic test results when applicable

Aliqopa (copanlisib) — CHRONOS-1:

Evaluated in a single-arm phase 2 study (CHRONOS-1) in relapsed follicular lymphoma with ORR ~59% and median duration of response ~12.2 months; treatment continued until disease progression or unacceptable toxicity.

Phase 2 single-arm data

Piqray (alpelisib) — SOLAR-1: Phase 3 randomized SOLAR-1 trial demonstrated improved PFS in PIK3CA-mutant HR+ HER2- advanced breast cancer (median PFS 11.0 vs 5.7 months for alpelisib plus fulvestrant vs fulvestrant alone).

Phase 3 randomized data

Itovebi (inavolisib) — INAVO120: Phase 3 INAVO120 trial showed a PFS benefit when Itovebi was added to palbociclib and fulvestrant in PIK3CA-mutated HR+ HER2- advanced breast cancer (HR 0.43; median PFS 15.0 vs 7.3 months).

Phase 3 randomized data

Initial therapy (summary)

Initial therapy summary: Policy has been updated over time to add and remove covered indications per FDA approvals, withdrawals, and guideline updates; see full policy for per-drug initial therapy criteria.

Detailed per-drug initial therapy criteria located in respective sections

Trial-based continuation rules

Authorization duration

Duration of authorization: Non-formulary exception authorizations and other approvals for drugs listed in this policy may be approved for up to 12 months as an operational limit.up to 12 months

See prior authorization section for drug-specific initial lengths

Zydelig (idelalisib)

Quantity / Dose Limit300 mg total daily (150 mg twice daily)

Indication (policy)Relapsed chronic lymphocytic leukemia (CLL) in combination with rituximab for individuals where rituximab alone would be appropriate

Not recommendedNot indicated or recommended for first‑line treatment

Safety noteIdelalisib carries FDA safety alerts and boxed warnings for serious/fatal toxicities; use restricted to labeled indications

Other PI3K inhibitors in this policy are oral and dispensed via pharmacy benefit.

Policy implicationTherapies indicated for CLL frequently apply to SLL as they represent the same disease spectrum

inv-28: PI3K isoforms — Class I PI3Ks and isoforms summary

ClassClass I PI3Ks — catalytic p110 subunit family

Isoform listp110α, p110β, p110γ, p110δ

Pharmacologic noteApproved PI3K inhibitors selectively target one or more isoforms; isoform specificity contributes to therapeutic indications and safety

Examples of isoform targetingAlpelisib targets alpha; copanlisib targets alpha and delta; duvelisib targets gamma and delta; idelalisib targets delta

inv-29: PROS — PIK3CA-related overgrowth spectrum definition

TermPIK3CA‑related overgrowth spectrum (PROS)

DefinitionA heterogeneous group of disorders associated with vascular malformations and segmental overgrowth, often early‑onset and progressive

Clinical severityCan be associated with high morbidity and mortality; systemic therapy may be required for severe manifestations

Therapeutic noteAlpelisib (Vijoice/Piqray) inhibits PI3Kα and is approved for severe PROS with documented PIK3CA mutation and measurable target lesion

inv-30: PI3K inhibitor agents — list and brief classification

ClassPI3K inhibitor agents (small‑molecule) targeting Class I PI3Ks

Representative agentsAlpelisib (Piqray/Vijoice), Copanlisib (Aliqopa), Duvelisib (Copiktra), Idelalisib (Zydelig)

Other referenced agentsLeniolisib (Joenja), Capivasertib (Truqap), Inavolisib (Itovebi), Umbralisib (Ukoniq) — note: umbralisib removed from policy following withdrawal

Clinical contextsUsed in B‑cell malignancies, HR+/HER2‑ PIK3CA‑mutant breast cancer, genetic syndromes (APDS, PROS) depending on agent specificity

2021-05-01agent_added

Added coverage criteria for Ukoniq (umbralisib) for the treatment of MZL and FL.

2022-03-01coverage_removal

Removed Copiktra (duvelisib) coverage for relapsed or refractory follicular lymphoma after manufacturer withdrew that indication; removed some Aliqopa (copanlisib) coverage for CLL and SLL reflecting FDA/NCCN alignment (effective June 3, 2022 for Aliqopa policy changes).

2022-07-01agent_removed

Ukoniq (umbralisib) removed from the policy for all FDA-approved indications following FDA withdrawal due to safety concerns.

2022-10-01coverage_added

Added coverage for Vijoice and Piqray (alpelisib) for treatment of PIK3CA-related overgrowth spectrum (PROS); moved Piqray to a separate policy with no change to coverage criteria.

2023-07-01coverage_added

Added coverage criteria for Joenja (leniolisib) for treatment of activated PI3K delta syndrome (APDS) in individuals 12 years and older.

2024-03-01coverage_update

Added coverage criteria for Truqap (capivasertib) for certain breast cancer populations and removed Zydelig (idelalisib) coverage for specific follicular lymphoma and small lymphocytic lymphoma indications after those uses were removed from prescribing information.

2024-06-01coverage_expansion

Updated Piqray (alpelisib) coverage criteria to include treatment of certain pre- and peri-menopausal women with breast cancer.

2025-03-01coverage_added_and_clarifiedLatest

Clarified that medications listed are subject to FDA dosing and administration; clarified non-formulary exception authorizations may be approved up to 12 months; and added coverage criteria for Itovebi (inavolisib).