ModifiedPremera BluecrossPolicy N/A

Drugs for Rare Diseases (pharmacy/medical policy)

Defines medical necessity, site-of-service review, and coverage criteria for IV, injectable, and selected oral therapies for multiple rare inherited diseases; applies to providers requesting drug coverage and administration site reviews.

Policy Summary

PayerPremera Bluecross

PolicyDrugs for Rare Diseases (pharmacy/medical policy)

Policy CodePolicy N/A

Change TypeRevised — coverage criteria and documentation updates

Effective DateApr 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with diagnostic confirmation (genetic or biochemical), prescriber specialty attestation, and required lab thresholds to support approval.

SourceLink

POLICY UPDATE CHANGES

This policy has been revised.

Added coverage criteria for Zycubo (copper histidinate) for Menkes disease and background on Menkes disease.

Added Kygevvi (doxecitine and doxribtimine) summary of evidence including survival benefit versus external controls in individuals with TK2d onset ≤12 years.

Updated Oxlumo coverage criteria to remove exclusion for individuals with kidney transplant and clarified elevated plasma oxalate (POx) documented as ≥20 µmol/L or 1.76 mg/L.

Updated multiple drug age indications and coverage criteria (e.g., Imcivree age lowered to 2 years; Livmarli age adjustments and PFIC subgroup exclusion; Brineura age broadened to <18 years).

20+drugs listed for site-of-service review

~30+distinct drug entries in excerpt

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 monthstypical approval period

6 monthsinitial approval for select agents

≥13site-of-service review age threshold

13+pharmacy-managed drugs

Coverage Criteria and Drug-Specific Medical Necessity

Burosumab (Crysvita) — Pediatric and Adult Evidence Summary

Crysvita (burosumab) — Pediatric and Adult Evidence Summary

ALL of the following

Crysvita (burosumab) is indicated for X-linked hypophosphatemia (XLH) in pediatric and adult individuals and for FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO).
Evidence: pediatric Phase 2 open-label trials and adult Phase 3 randomized trial show improvements in radiographic rickets severity, growth velocity, walking distance, serum phosphorus, fracture healing, and measures of physical function.
Pediatric evidence: two 64-week Phase 2 open-label trials (total n=65 children aged 1–12 years) demonstrated significant improvements in Thacher rickets severity score, RGI-C, and growth measures; functional measures (walking distance) improved versus baseline.
Refer to clinical trial data for magnitudes of effect and age groups.
Adult evidence: a randomized, double-blind, placebo-controlled Phase 3 trial in 134 adults with XLH showed significantly more individuals achieved midpoint serum phosphorus >2.5 mg/dL with burosumab versus placebo, improved healing of active fractures/pseudofractures, and improvements in physical function and stiffness; ongoing extension demonstrated sustained benefits to 48 weeks.
Clinical benefits include fracture healing and functional improvements; pain results were mixed.
Initial approval and re-authorization: Initial therapy may be approved up to 12 months; continued therapy may be approved up to 12 months when medical necessity criteria are met and chart notes demonstrate continued positive clinical response.

Elosulfase alfa (Vimizim) — MPS IVA

Elosulfase alfa (Vimizim) — MPS IVA Evidence Summary

ALL of the following

Vimizim (elosulfase alfa) is indicated for individuals with mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome).
Evidence: randomized, double-blind, placebo-controlled trial (N=176, age ≥5 years) demonstrated a statistically significant improvement in 6-minute walk test at Week 24 for weekly dosing versus placebo.
Clinical outcomes: Vimizim 2 mg/kg once weekly resulted in a 20-meter increase in 6-minute walk distance versus a 9.9 m change with placebo (p=0.02); common adverse reactions include pyrexia, vomiting, headache, nausea, and abdominal pain.
Vimizim includes a boxed warning for life-threatening anaphylactic reactions; monitor per labeling.
Initial and continuation therapy: Initial therapy may be approved up to 12 months; re-authorization up to 12 months when medical necessity criteria and positive clinical response are documented.

Dichlorphenamide (Keveyis) — Primary Periodic Paralysis

Dichlorphenamide (Keveyis/Ormalvi/generic) — Primary Periodic Paralysis Evidence Summary

ALL of the following

Keveyis (dichlorphenamide) is indicated for adults with primary hyperkalemic or hypokalemic periodic paralysis when criteria are met including documented regular episodes of weakness averaging at least once per week and normal TSH.
Evidence: randomized 9-week Phase III trial with 52-week open-label extension demonstrated improvement in attack rates and severity in completers; clinical responder data support use.
Prior therapy requirement: Prior therapy with acetazolamide must be ineffective, not tolerated, or contraindicated; trial of generic dichlorphenamide (or Ormalvi) and failure/intolerance should be documented prior to brand use when applicable.
Dose limit: up to 200 mg daily (4 tablets).
Initial authorization: may be approved up to 3 months for Keveyis; re-authorization up to 12 months when clinical response is documented (reduced attack frequency/severity).
Generic formulations follow similar criteria as indicated.

Triheptanoin (Dojolvi) — LC-FAOD

Triheptanoin (Dojolvi) — Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Evidence Summary

ALL of the following

Dojolvi (triheptanoin) is a triglyceride used as supplemental therapy for molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD).
Evidence: one Phase 2 randomized controlled trial vs trioctanoin (n=32) showed improvement in cardiac mass/function; other endpoints were mixed; supportive single-arm studies and case series exist.
Coverage criteria highlights: diagnosis must be molecularly confirmed; trial and failure or intolerance to over-the-counter MCT oil is required unless contraindicated; elevated mean CK >2×ULN or >500 U/L is required; for individuals ≥7 years, documentation of ≥4 ED/hospitalization events related to disease severity in last 2 years; provider attestation of low-fat/high-carbohydrate diet required.
Initial therapy may be approved up to 12 months; continued therapy contingent on documented positive clinical response and tolerance.
Safety: SAEs related to hospitalizations occurred in studies (mostly viral infections or rhabdomyolysis); GI adverse events are common and may require dose adjustment.

Setmelanotide (Imcivree) — POMC/LEPR Deficiency Obesity

Setmelanotide (Imcivree) — POMC/LEPR (and related) Deficiency Obesity Evidence Summary

ALL of the following

Imcivree (setmelanotide) is indicated for chronic weight management in individuals (age ≥2 years) with monogenic or syndromic obesity due to POMC, PCSK1, or LEPR deficiency and for certain individuals with Bardet-Biedl syndrome per criteria.
Evidence: two Phase 3 trials in POMC and LEPR deficiency (total n=21) met primary endpoint of ≥10% weight loss at ~52 weeks with large mean weight reductions; Phase 2 and extension data support durability.
Genetic confirmation: obesity must be due to pathogenic or likely pathogenic (or VUS as specified) variants in POMC, PCSK1, or LEPR genes as confirmed by genetic testing; baseline weight thresholds defined by BMI (adults) or percentiles (children).
Dose limited to 3 mg once daily; prescribed by/with geneticist or endocrinologist.
Safety and monitoring: common adverse events include injection site reactions, hyperpigmentation, nausea/vomiting; suicidal ideation/behavior reported in some treated individuals—monitor psychiatric status. Initial therapy may be approved up to 6 months (POMC/LEPR) or up to 12 months for BBS; re-authorization requires documented weight loss (≥5% adult) or positive clinical response in pediatrics.

Lumasiran (Oxlumo) — PH1 Evidence Summary and Diagnostic Update

Lumasiran (Oxlumo) — Primary Hyperoxaluria Type 1 Evidence Summary and Updated Diagnostic Documentation

ALL of the following

Oxlumo (lumasiran) is indicated to lower urinary and plasma oxalate levels in pediatric and adult individuals with primary hyperoxaluria type 1 (PH1).
Evidence: ILLUMINATE A (randomized, double-blind in individuals ≥6 years) and ILLUMINATE B/C (younger children and those with reduced eGFR/on dialysis) demonstrated substantial reductions in urinary oxalate and plasma oxalate across populations.
Diagnostic documentation (updated 2026): diagnosis requires PH1 confirmed by AGXT gene mutation OR liver biopsy demonstrating AGT deficiency. Baseline biomarker thresholds accepted: 24-hour urinary oxalate (UOx) ≥0.7 mmol/24hr/1.73 m2 OR for ≤5 years, spot UOx:creatinine above age-specific ULN OR plasma oxalate (POx) ≥20 µmol/L (1.76 mg/L).
Prior policy exclusion for kidney transplant was removed (2026 update); individuals with prior kidney transplant may be considered per revised criteria.
Dosing and prescriber specialty: maintenance dosing by weight per labeling; Oxlumo should be prescribed by or in consultation with nephrologist, urologist, or geneticist. Initial therapy may be approved up to 6 months; re-authorization up to 12 months when urine or plasma oxalate decreases from baseline and clinical response/tolerability documented.

Rivfloza (Nedosiran) — PH1/PH2 RNAi Evidence Summary

Nedosiran (Rivfloza) — PH1/PH2 RNAi Agent Evidence Summary

ALL of the following

Rivfloza (nedosiran) is an RNAi therapeutic that lowers urinary oxalate by inhibiting hepatic LDH and is studied for PH1 and PH2.
Evidence: PHYOX2 Phase 2 randomized trial (n≈35; ages ≥6) showed significant reductions in 24-hour urinary oxalate AUC and percent change from baseline versus placebo, with sustained reductions in extension studies for PH1 patients.
Eligibility and monitoring: approved age criteria generally ≥2 years depending on formulation and weight-based dosing; requires genetic confirmation of AGXT mutation for PH1 and eGFR thresholds (e.g., ≥30 mL/min/1.73 m2) per policy; plasma oxalate ≥20 µmol/L acceptable. Maintenance dosing limits defined by age/weight strata. Initial therapy may be approved up to 6 months; re-authorization up to 12 months when urine or plasma oxalate decreases from baseline and tolerability documented.
Most common adverse event: mild injection-site reactions.

Kygevvi (doxecitine and doxribtimine) — TK2 Deficiency

Kygevvi (doxecitine and doxribtimine) — TK2 Deficiency Evidence Summary

ALL of the following

Kygevvi (doxecitine and doxribtimine) provides exogenous thymidine nucleosides intended to restore mitochondrial DNA function in individuals with thymidine kinase 2 deficiency (TK2d).
Evidence: approval supported by one Phase II study, two retrospective chart reviews, and expanded access data (total N≈82 treated pediatric and adult individuals with symptom onset ≤12 years).
Clinical outcomes: survival analyses using matched external controls showed treatment reduced risk of death by approximately 86% (95% CI: 61%, 96%) from treatment start in matched pediatric-onset populations; median treatment duration ~4 years in treated cohorts.
Common adverse reactions include GI symptoms and transaminase elevations.
Coverage considerations: diagnosis must be confirmed by genetic testing detecting TK2 variants; documentation of symptom onset age supports phenotype classification; therapy should be prescribed by/with a neurologist. Initial therapy may be approved up to 12 months; re-authorization contingent on documented clinical benefit and tolerability.

Policy Additions and Historical Criteria Updates

Policy Additions and Historical Criteria Updates (selected highlights)

ALL of the following

This policy has undergone multiple interim and annual updates adding agents, revising age criteria, and modifying diagnostic and exclusion criteria over time; highlights include additions of Dojolvi (triheptanoin), Oxlumo (lumasiran), Imcivree (setmelanotide), Rivfloza (nedosiran), Kygevvi, and many enzyme replacement and specialty therapies between 2020–2026.
See Appendix revision history for dated entries and details.
Notable updates: 2024 included additions for Voydeya, Xolremdi, Hemangeol, and expanded Livmarli PFIC criteria; 2026 update removed Oxlumo transplant exclusion and clarified plasma oxalate threshold (≥20 µmol/L or 1.76 mg/L); multiple HCPCS/ coding updates and site-of-service review implementations occurred across revisions.
Providers should reference the Appendix history for full timeline and coding changes.
Operational implication: prior authorization, documentation of genetic/molecular confirmation where required, baseline and follow-up biomarker thresholds, prescriber specialty requirements, dose limits, and initial vs re-authorization timeframes reflect the historical and current policy changes and must be followed for coverage determinations.

Initial Therapy Authorization Rules

Re-authorization and Maintenance Criteria

Step Therapy and Prior-Fail Requirements

Requirement	Example / Notes
Prior use or inadequate response to specified therapies may be required before approving an alternative agent	Example: Pombiliti + Opfolda requires documentation of inadequate response to prior ERT (e.g., Nexviazyme or Lumizyme) with baseline FEV1 30–85% predicted and inability to complete 6MWT ≥75 m despite prior ERT (see Pombiliti+Opfolda criteria)
Documentation of trial length and reason for discontinuation (lack of efficacy, intolerance, contraindication) should be provided	Example: For some agents initial approval periods vary (commonly up to 6–12 months); Pombiliti+Opfolda initial therapy may be approved up to 12 months

Requirement	Agents / Examples
Must try and fail lower‑cost generic or OTC alternatives unless contraindicated or intolerant	Example: Cystadane (betaine anhydrous) requires prior trial of generic betaine anhydrous with inadequate response or intolerance documented
Must document trial of OTC MCT oil and failure/intolerance when applicable	Example: Dojolvi (triheptanoin) requires tried/failed or intolerant to OTC MCT oil unless contraindicated

Requirement	Specific agents / Notes
Prior trial of listed agents for cholestatic pruritus required	Bylvay (odevixibat) and Livmarli (maralixibat) require prior trial of ursodiol AND one of cholestyramine or rifampin before approval
Document dose and response to prior agents	Example: Bylvay dose limited to 6 mg once daily; Livmarli dose limited to 28.5 mg once daily; prior therapy response must be noted in chart

Requirement	Policy implication / Notes
Prior rituximab trial required unless contraindicated	Enjaymo (sutimlimab-jome) requires tried and failed rituximab (monotherapy or combination) unless contraindicated; lack of documented rituximab trial may lead to denial
Enjaymo must not be used with rituximab and vaccinations required ≥2 weeks prior to initiation	Hemoglobin ≤10.0 g/dL and bilirubin above normal are additional lab thresholds for Enjaymo initiation

Requirement	Combination / Rationale
Use in combination with miglustat (or generic miglustat) is required where labeled	Miplyffa (arimoclomol) approval and pivotal trial data require concomitant miglustat; prior authorization must confirm concurrent miglustat therapy
Brand versus generic miglustat considerations	Policy notes explain use of generic miglustat in combination and restrictions on substitution for brand formulations when applicable

Issue	Coverage / Step implication
Benefit routing (pharmacy vs medical) impacts authorization workflow	Some therapies are managed via pharmacy benefit, some via medical benefit, and some via both; benefit assignment determines prior authorization path and may affect whether step requirements are enforced under pharmacy or medical review
Examples of benefit assignment	Aqneursa, Bylvay, Keveyis managed through pharmacy benefit; Aldurazyme, Lumizyme, Xenpozyme managed through medical benefit; Besremi, Oxlumo managed through both—this affects routing of step/failure documentation

Context	How comparative data may influence steps
Comparative efficacy data can inform preference or step decisions	Example: PROPEL trial compared Pombiliti+Opfolda vs alglucosidase alfa (active comparator); these comparative results may guide step or switching decisions for late‑onset Pompe disease
Documentation to support switching based on comparative benefit	Prior authorization should include trial data showing inadequate response to comparator ERTs and rationale for switching to combination therapy (Pombiliti+Opfolda)

Consideration	Policy example
Consider prior acetazolamide use when evaluating dichlorphenamide (Keveyis/Ormalvi)	Dichlorphenamide evidence includes trials that used dose conversions from acetazolamide; document prior carbonic anhydrase inhibitor use (acetazolamide) or intolerance if relevant
Step implication	Policy historically required trial/failure of generic dichlorphenamide before brand Keveyis; prior acetazolamide exposure may be considered in clinical decision-making

Consideration	Policy implication
Besremi evidence compared to hydroxyurea may inform sequencing	Trials (PROUD/CONTINUATION) showed differing response kinetics; prior trial or intolerance to hydroxyurea or best available therapy may be considered before switching to Besremi
Documentation recommended	Authorization should document prior hydroxyurea/BAT use and reason for switching (lack of durable response or intolerance); long‑term extension data support ongoing benefit with Besremi

Point	Step implication
Miplyffa approval is tied to concomitant miglustat use	Policy requires Miplyffa to be used in combination with miglustat; prior authorization must confirm concurrent miglustat therapy and that Miplyffa is not used with Aqneursa
Implication for step therapy	Authorization could require trial on combination (Miplyffa + miglustat) per labeled trial data rather than Miplyffa monotherapy

Scenario	Examples / Historical notes
Step prior to brand therapy—require trial/failure of generic first	Historical example: policy required trial and failure of generic dichlorphenamide prior to brand Keveyis (noted in 07/01/23 update)
Other examples	Policy updates added generic-first requirements for other drugs where applicable; documentation of generic trial and reason for failure should be provided

Historical practice	Examples
Prior trial of generic agents historically required before brand approval in some cases	Example: generic dichlorphenamide trial required prior to brand Keveyis (07/01/23); similar generic-first requirements applied to Zavesca/miglustat brand substitutions
Documentation expectation	Provide dates, duration, dose, and reason for discontinuation of generic trial; if contraindicated or allergic, document rationale to waive generic requirement

Billing Codes and Clinically Relevant Thresholds

Covered HCPCS/J-codes (selection)HCPCSCovered

G0138	Intravenous infusion of cipaglucosidase alfa-atga, including provider/supplier acquisition and clinical supervision of oral administration of miglustat in preparation of receipt of cipaglucosidase alfa-atga (Opfolda with Pombiliti).
J0180	Injection, agalsidase beta (Fabrazyme), 1 mg.
J0217	Injection, velmanase alfa-tycv (Lamzede), 1 mg.
J0218	Injection, olipudase alfa-rpcp (Xenpozyme), 1 mg.
J0219	Injection, avalglucosidase alfa-ngpt (Nexviazyme), 4 mg.
J0221	Injection, alglucosidase alfa (Lumizyme), 10 mg.
J0223	Injection, givosiran (Givlaari), 0.5 mg.
J0224	Injection, lumasiran (Oxlumo), 0.5 mg.
J0567	Injection, cerliponase alfa (Brineura), 1 mg.
J0584	Injection, burosumab-twza (Crysvita), 1 mg.

1–10 of 20

1/2

Additional HCPCS/J-codesHCPCSCovered

J2508
J2840	Injection, sebelipase alfa (Kanuma), 1 mg.
J2860	Injection, siltuximab (Sylvant), 10 mg
J2998	Injection, plasminogen, human-tvmh (Ryplazim), 1 mg.
J3060	Injection, taliglucerase alfa (Elelyso), 10 units.
J3241	Injection, teprotumumab-trbw (Tepezza), 10 mg.
J3385	Injection, velaglucerase alfa (Vpriv), 100 units.
J3397	Injection, vestronidase alfa-vjbk (Mepsevii), 1 mg.
J3490	Unclassified drugs (use to report: Rivfloza).
J3590	Unclassified biologics (Use to report: Cablivi, Besremi, Imcivree, Revcovi, and Voxzogo).

1–10 of 11

1/2

Covered J-codes (part 1)HCPCSCovered

G0138	Intravenous infusion of cipaglucosidase alfa-atga, including provider/supplier acquisition and clinical supervision of oral administration of miglustat in preparation of receipt of cipaglucosidase alfa-atga (Opfolda with Pombiliti).
J0180	Injection, agalsidase beta (Fabrazyme), 1 mg.
J0217	Injection, velmanase alfa-tycv (Lamzede), 1 mg.
J0218	Injection, olipudase alfa-rpcp (Xenpozyme), 1 mg.
J0219	Injection, avalglucosidase alfa-ngpt (Nexviazyme), 4 mg.
J0221	Injection, alglucosidase alfa (Lumizyme), 10 mg.
J0223	Injection, givosiran (Givlaari), 0.5 mg.
J0224	Injection, lumasiran (Oxlumo), 0.5 mg.
J0567	Injection, cerliponase alfa (Brineura), 1 mg.
J0584	Injection, burosumab-twza (Crysvita), 1 mg.

1–10 of 20

1/2

Covered J-codes (part 2)HCPCSCovered

J2508
J2840	Injection, sebelipase alfa (Kanuma), 1 mg.
J2860	Injection, siltuximab (Sylvant), 10 mg
J2998	Injection, plasminogen, human-tvmh (Ryplazim), 1 mg.
J3060	Injection, taliglucerase alfa (Elelyso), 10 units.
J3241	Injection, teprotumumab-trbw (Tepezza), 10 mg.
J3385	Injection, velaglucerase alfa (Vpriv), 100 units.
J3397	Injection, vestronidase alfa-vjbk (Mepsevii), 1 mg.
J3490	Unclassified drugs (use to report: Rivfloza).
J3590	Unclassified biologics (Use to report: Cablivi, Besremi, Imcivree, Revcovi, and Voxzogo).

1–10 of 11

1/2

Historical HCPCS/J code updates referencedHCPCS

J0567	HCPCS code added (reference in history)
J1458	HCPCS code added (reference in history)
J1931	HCPCS code added (reference in history)
J2840	HCPCS code added (reference in history)
J2860	HCPCS code added (reference in history)
J3210	Not present in excerpt but similar codes referenced; only codes explicitly listed are included

All HCPCS/J/C codes mentioned in appendix historyHCPCS

J0218	HCPCS code added (reference in history)
J0219	HCPCS code added (reference in history)
J0223	HCPCS code added (reference in history)
J0224	HCPCS code added (reference in history)
J0791	HCPCS code added earlier then removed/moved per history
J1202	HCPCS code added (reference in history)
J1203	HCPCS code added (reference in history)
J1302	HCPCS code added (reference in history)
J3397	HCPCS code added for Mepsevii
J3590	HCPCS code referenced multiple times

1–10 of 16

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inv-84: 24-hour urinary oxalate (UOx) excretion threshold

24‑hour UOx threshold>= 0.7 mmol/24hr/1.73 m2

Alternative for children <=5 yrsElevated spot UOx:creatinine above age‑specific ULN

Documentation contextUsed as an initiation/re-authorization biochemical criterion for Oxlumo and Rivfloza

inv-85: Mean creatine kinase (CK) threshold

Mean CK threshold> 2X upper limit of normal OR > 500 U/L

Age/sex reference

Prior Authorization, Documentation, and Prescriber Requirements

Denial Risk

Site-of-Service and Medical Necessity Review

Site-of-service medical necessity reviews apply to medical benefit-administered IV and injectable drugs and may affect where treatment is approved to be given. For individuals aged 13 and older the site-of-service (SOS) may be reviewed (hospital outpatient, infusion center, physician office, home infusion). SOS medical necessity criteria do not apply to Alaska fully‑insured members. Claims for drugs administered in a higher‑cost site (e.g., hospital outpatient) may be denied if SOS criteria are not met.

Applies to IV and injectable drugs managed under the medical benefit
SOS review limited to individuals aged ≥13 (site-of-service age criterion)
Alaska fully‑insured members exempt from SOS review per Alaska HB 226

Prior Authorization

Prior Authorization — Prescriber and Specialist Documentation

Prior authorization and prescriber/specialist requirements: many therapies require authorization and certain agents must be prescribed by or in consultation with a specialist (e.g., nephrologist, hematologist, geneticist, neurologist). Ensure the prescriber specialty and consultation documentation are included with the request.

Quantity and Dosing Limits

inv-205: Lumizyme (alglucosidase alfa) quantity limit

Lumizyme quantity limitDose prescribed must be no more than 20 mg/kg every 2 weeks

Concurrent use exclusionLumizyme must not be used concurrently with Nexviazyme

Initial approvalInitial therapy may be approved up to 12 months

inv-206: Yorvipath (palopegteriparatide) quantity/dose limit

Yorvipath quantity/dose limit30 mcg daily

Initial approval durationInitial therapy may be approved up to 12 months

Prescriber

Site-of-Service Rules and Preferred Settings

Note

Preferred medically necessary sites (office, infusion center, home) and hospital outpatient considered when criteria met

Preferred medically necessary sites include physician office, infusion center, or home infusion; hospital‑based outpatient may be medically necessary for the initial 90‑day course, re‑initiation after ≥6 months, or when patient risk factors or lack of local outpatient/home infusion options are documented.

Note

IV ERTs and SC biologics subject to site-of-service review examples

Several IV enzyme replacement therapies and some subcutaneous biologics are subject to site‑of‑service review; include site justification and any high‑risk clinical features when requesting hospital outpatient administration.

Note

Kanuma IV subject to site-of-service review

Kanuma (sebelipase alfa) IV is subject to site‑of‑service review; document clinical rationale if hospital outpatient administration is requested.

Background and Definitions

Lysosomal storage disorders and many other inherited enzyme or protein deficiencies are rare genetic conditions caused by absent or dysfunctional enzymes that lead to substrate accumulation and multi‑system disease. These disorders often require disease‑specific therapies such as enzyme replacement therapy (ERT), substrate reduction, gene‑directed or metabolic replacement therapies, and supportive care. Diagnostic confirmation typically relies on biochemical enzyme assays and/or genetic testing to document pathogenic variants; treatment decisions and authorization require documentation of diagnosis, appropriate specialist prescribing, and adherence to the agent‑specific criteria in this policy.

inv-148: Enzyme replacement therapy (ERT) definition

ERT definitionTherapy providing a functional enzyme to replace a deficient or nonfunctional endogenous enzyme

Clinical roleCommon primary treatment for lysosomal storage diseases

Diagnostic implicationOften requires enzyme assay or genetic confirmation before use

inv-149: Genetic or enzyme confirmation (definition)

Policy Changes and Revision History

03/01/21addition

Imcivree (setmelanotide), Oxlumo (lumasiran), Zokinvy (lonafarnib), Sucraid (sacrosidase) and other therapies were added to the policy with associated coverage criteria and HCPCS coding updates.

09/03/21coding_update

HCPCS codes J0567, J1458, J1931, J2840, J2860, and J9210 were added and became effective for dates of service on or after September 3, 2021 following provider notification.

01/01/22coding_and_criteria_update

Policy Summary

PayerPremera Bluecross

PolicyDrugs for Rare Diseases (pharmacy/medical policy)

Policy CodePolicy N/A

Change TypeRevised — coverage criteria and documentation updates

Effective DateApr 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with diagnostic confirmation (genetic or biochemical), prescriber specialty attestation, and required lab thresholds to support approval.

SourceLink

On This Page

Appendix contains full chronological change log with effective dates.

Compare to age‑ and sex‑specific pediatric CK reference ranges in Appendix Table 1

Use caseEntry criterion for Dojolvi (triheptanoin) in LC‑FAOD

inv-86: Urinary or plasma ALA/PBG at diagnosis

Diagnostic ALA/PBG thresholdUrinary or plasma ALA or PBG greater than the laboratory upper limit of normal at diagnosis

Required for AHP diagnosisElevated ALA/PBG plus compatible clinical attacks and confirmatory gene testing (ALAD, CPOX, HMBS, PPOX)

Role in reauthorizationRe‑auth requires ALA/PBG not increased from baseline with clinical improvement

inv-87: Yorvipath dose limit

Daily dose limit30 mcg daily

Prescriber requirementPrescribed by or in consultation with an endocrinologist

Concurrent therapyMust be on or have tried calcium and vitamin D; serum 25(OH)D must be normal

inv-88: 24-hour urinary oxalate (UOx) duplicate threshold

Duplicate UOx threshold>= 0.7 mmol/24hr/1.73 m2 (same threshold used for confirmation)

Pediatric alternativeFor ≤5 years use elevated spot UOx/creatinine above age‑specific ULN

Applies toOxlumo and Rivfloza initiation eligibility and monitoring

inv-89: Plasma oxalate (POx) threshold

Plasma oxalate (POx) threshold>= 20 µmol/L (1.76 mg/L)

Acceptable documentationPOx >=20 µmol/L accepted for Oxlumo coverage; liver biopsy showing AGT deficiency or AGXT mutation also acceptable

RoleUsed as alternative biochemical criterion when 24‑hr UOx not available or in reduced renal function

inv-90: Hemoglobin (Enjaymo / Pyrukynd) threshold

Hemoglobin threshold<= 10.0 g/dL

Applies toEnjaymo (CAD) and Pyrukynd (PKD) entry criteria requiring Hgb ≤10.0 g/dL

PrescriberTherapies typically require hematology prescribing or consultation

inv-91: DLCO (adults with ASMD)

DLCO threshold (adults, ASMD)<= 70% predicted

Diagnostic requirementASMD confirmation by enzyme assay and SMPD1 sequencing plus baseline DLCO for adults

UseEligibility for Xenpozyme (olipudase alfa) for non‑CNS ASMD

inv-92: PNH clone size threshold

PNH clone size thresholdGranulocyte or monocyte clone size >= 15%

ContextRequired to confirm PNH for Voydeya (danicopan) eligibility

Additional requirementCompleted ≥6 months of Soliris or Ultomiris and residual anemia/LDH criteria

inv-93: DLCO duplicate threshold

DLCO duplicate threshold≤ 70% predicted

Applies toAdult DLCO severity threshold for Xenpozyme eligibility

DocumentationBaseline DLCO required for authorization and re‑auth monitoring

inv-94: Absolute neutrophil count (ANC)

ANC threshold≤ 400 cells/µL

Applies toXolremdi (mavorixafor) entry criterion for WHIM syndrome

PrescriberPrescribed by or in consultation with immunologist or hematologist

inv-95: Antigenic levels of α 1-PI

Antigenic α1‑PI level goalMaintenance blood serum levels above 11 µM

Therapeutic rationaleLevel thought to provide antineutrophil elastase protection

UseReference definition used for α1‑PI replacement therapies

inv-96: GL-3 Inclusion Score

GL‑3 Inclusion Score range0 (normal) to 3 (severe inclusions)

MeasurementHistologic score of GL‑3 inclusions in renal interstitial capillary endothelial cells

ContextReported as trial endpoint for Fabry disease enzyme therapies

inv-97: Clinical endpoints reported (examples)

Examples of clinical endpointsChange in 6‑minute walk distance (meters); percent predicted FVC; plasma lyso‑Gb3 decrease; mean annualized eGFR slope

Trial‑specific exampleElfabrio: plasma lyso‑Gb3 decreased 31.5% at Month 12; mean eGFR slope improvements reported

Use in authorizationEndpoints used to document clinical response at re‑authorization

inv-98: Plasma oxalate (POx) accepted threshold for Oxlumo documentation

Accepted POx threshold for Oxlumo documentation>= 20 µmol/L (1.76 mg/L)

Alternate diagnosis documentationLiver biopsy demonstrating AGT deficiency or AGXT mutation acceptable; kidney transplant no longer an exclusion

RoleUsed to support Oxlumo initiation and coverage when 24‑hr UOx unavailable or in impaired renal function

inv-99: Pediatric CK reference ranges (appendix table)

Pediatric CK reference ranges (selected examples)0–90 days: male 28–300 U/L; female 42–470 U/L; 15–18 years: male 33–145 U/L; female 27–140 U/L

UsageReference appendix Table 1 for age/sex‑specific CK ranges when interpreting elevated CK

ContextUsed to assess Dojolvi eligibility where mean CK >2x ULN or >500 U/L

Examples: Oxlumo and Rivfloza require nephrologist/urologist/geneticist involvement; Voydeya and Enjaymo require hematology involvement; Miplyffa and miglustat require pediatric neurology or clinical geneticist input

Documentation Required

Baseline Diagnostic and Clinical Documentation

Baseline diagnostic and clinical documentation must be provided with initial prior authorization requests. This includes disease‑specific confirmation (enzyme assays, gene sequencing, or biopsy where noted), baseline functional measures, and prior therapy trials when required.

Pompe disease (Pombiliti/Opfolda, Lumizyme, Nexviazyme): GAA enzyme deficiency or GAA gene mutation; baseline FEV1 and 6MWT documentation for Pombiliti (FEV1 30–85% predicted; 6MWT <75 m)
ASMD (Xenpozyme): ASMD biochemical enzyme assay and SMPD1 gene sequencing; for adults DLCO ≤70% predicted noted
Fabry, Pompe, Gaucher and other ERTs: confirmatory enzyme assay or gene sequencing as specified
Provide documentation of prior inadequate response or intolerance to alternative/required therapies where policy requires trial and failure

Documentation Required

Laboratory Monitoring and Oxlumo POx Documentation

Laboratory monitoring and biochemical thresholds used for eligibility and reauthorization must be included in the record. For Oxlumo (lumasiran) requests include urinary oxalate (24‑hour or spot UOx/Cr) and plasma oxalate (POx) measurements as applicable; reauthorization should show reduction in urine or plasma oxalate or clinical response.

Oxlumo: 24‑hour UOx ≥0.7 mmol/24hr/1.73m2 (or age‑adjusted spot UOx/Cr in ≤5 years) OR plasma oxalate ≥20 µmol/L (1.76 mg/L) acceptable diagnostic thresholds
Reauthorization: chart notes should document decreased urine oxalate or plasma oxalate and clinical tolerability
Givlaari: include elevated urinary or plasma PBG or ALA at diagnosis and subsequent monitoring showing no increase from baseline for reauthorization

Prior Authorization

Combination Therapy and Concurrency Confirmation

Concurrent therapy and combination‑use documentation: when an agent is approved only in combination (or is not to be used concurrently with another specified agent), include documentation confirming intended combination or absence of prohibited concurrent agents.

Pombiliti (cipaglucosidase alfa‑atga) must be used concurrently with Opfolda (miglustat); document co‑administration and do not combine with Nexviazyme or Lumizyme
Miplyffa (arimoclomol) must be used in combination with miglustat and not used with Aqneursa
Voydeya (danicopan) requires background Soliris or Ultomiris therapy documented (prior 6 months of complement inhibitor therapy as specified)

Step Therapy

Prior Therapy Trials / Step Therapy Documentation

Prior therapy trials and step‑therapy requirements: include records of prior trials, intolerance, or inadequate response when policy requires step therapy or trial of alternatives. If policy lists a specific required prior agent, document dates, doses, and reason for discontinuation or inadequate response.

Examples: Bylvay/Livmarli — document trials of ursodiol plus cholestyramine or rifampin for cholestatic pruritus prior to Bylvay/Livmarli
Enjaymo (sutimlimab‑jome) — document trial of rituximab unless contraindicated
Voydeya — document prior complement inhibitor therapy and residual anemia/LDH criteria

Prior Authorization

Authorization Duration and Reauthorization Requirements

Authorization duration and reauthorization expectations: initial approvals are typically limited (commonly 6–12 months; some agents have different initial limits such as 90 days for Cablivi). Reauthorization requires documentation of ongoing clinical benefit, tolerability, and relevant laboratory or functional improvements as specified by the drug‑specific criteria.

Cablivi initial therapy up to 90 days; continuous use beyond 90 days considered investigational
Most drugs: initial approval up to 6–12 months with reauthorization up to 12 months when criteria and documented clinical response are met
Oxlumo: initial up to 6 months; reauthorization requires decrease in urine or plasma oxalate or clinical response

Billing Rule

Drug Coding and Benefit Assignment

Coding and billing implications: use the correct HCPCS/J‑codes for medical benefit claims and report unclassified codes J3490/J3590 when indicated (policy lists drugs that should be reported via unclassified codes). Incorrect coding can affect benefit assignment and trigger SOS review or claim denial.

Use listed HCPCS codes (e.g., J1203 for cipaglucosidase alfa‑atga, J1202 for miglustat reporting guidance)
Report certain agents via J3490/J3590 when specifically instructed (e.g., Rivfloza via J3490; specified biologics via J3590)
Benefit assignment (medical vs pharmacy) affects prior authorization pathway and site‑of‑service review

Prescribed by or in consultation with an endocrinologist

inv-207: Yorvipath (palopegteriparatide) duplicate entry (same chunk)

Duplicate Yorvipath entryDose limit: 30 mcg daily (see prior entry)

ContextListed as quantity/dose restriction in policy updates

UseApplies to hypoparathyroidism coverage criteria

inv-208: Aqvesme (mitapivat) quantity limit

Aqvesme quantity limit56 tablets per 28 days (100 mg twice daily)

Dose cap100 mg twice daily

PrescriberPrescribed by or in consultation with a hematologist

inv-209: Keveyis/Ormalvi (dichlorphenamide) quantity limit

Keveyis/Ormalvi quantity limit200 mg daily (4 tablets)

Prior therapyPrior trial of acetazolamide/generic dichlorphenamide or documentation of intolerance required

Initial approvalInitial therapy may be approved up to 3 months

inv-210: Sucraid (sacrosidase) quantity limit

Sucraid quantity limitNo more than 360 mL every 4 weeks

Diagnostic confirmationGenetic SI variants (2 pathogenic) or disaccharidase assay with sucrase <10th percentile required

PrescriberPrescribed by or in consultation with gastroenterologist

inv-211: Oxlumo (lumasiran) dosing — weight-based

Oxlumo dosing approachWeight‑based maintenance dosing by strata: <10 kg: 3 mg/kg monthly; 10–<20 kg: 6 mg/kg every 3 months; >=20 kg: 3 mg/kg every 3 months

Initial approvalInitial therapy may be approved up to 6 months; re‑auth up to 12 months with decreased urine/POx

Transplant noteHas not received liver transplant previously (policy update removed kidney transplant exclusion)

inv-212: Besremi maximum dose

Besremi maximum doseNo more than 500 mcg every 2 weeks

IndicationFor polycythemia vera in adults per 2016 WHO criteria

AuthorizationInitial therapy may be approved up to 24 months per dosing note

inv-213: Voxzogo weight-based dosing bands

Voxzogo dosing bandsWeight‑based daily dosing bands (examples: 10–11 kg 0.24 mg QD; up to 60–89 kg 0.7 mg QD)

EligibilityChildren with achondroplasia, open growth plates and growth velocity >=1.5 cm/yr

PrescriberPrescribed by or in consultation with specialist

inv-214: Voydeya daily dose

Voydeya daily dose limit600 mg daily

Combination requirementPrescribed in combination with Soliris or Ultomiris after >=6 months of C5 inhibitor therapy

Vaccination requirementVaccinate against N meningitidis, S pneumoniae, H influenzae >=2 weeks prior

inv-215: Various drug-specific dosing examples (Xenpozyme, Lamzede, Ctexli, Xolremdi, Forzinity)

Various example dosingExamples include: Xenpozyme 3 mg/kg q2w; Lamzede 1 mg/kg weekly; Ctexli 750 mg daily; Xolremdi 400 mg daily; Forzinity 40 mg daily

ContextRepresentative agent‑specific maintenance dosing examples from policy

PrescribingEach agent requires specialist prescribing/consultation per criteria

inv-216: Sucraid quantity limit added (historical change)

Sucraid quantity limit (historical addition)Quantity limit added (360 mL/4 weeks) per 2023 update

HistoryQuantity limit inserted in policy update history

ImplicationApplies to ongoing authorization and pharmacy benefit limits

inv-217: Nexviazyme max dose by weight bands

Nexviazyme max dose by weight<30 kg: 40 mg/kg every 2 weeks; >=30 kg: 20 mg/kg every 2 weeks

ContextMaximum maintenance dosing specified in quantity limits section

Site‑of‑serviceNexviazyme subject to site‑of‑service review per history notes

inv-218: Lumizyme dosage limit added (historical)

Lumizyme dosage limit added (history)Dosage limit added to policy in historical updates (see Appendix entries)

ImplicationReinforces 20 mg/kg q2w maximum dosing for Lumizyme

ReferenceAppendix coding/history entries document addition

inv-219: Sucraid quantity limit added (historical)

Sucraid quantity limit added (history)Historical update added quantity limit for Sucraid to the policy

Current limit360 mL every 4 weeks per medical necessity section

ReferenceSee Appendix history for 2023 updates

Billing Rule

Infusion-related billing codes and implication for setting

Infusion‑related billing codes (example: G0138 and other HCPCS J‑codes) indicate infusion setting and supervision; submit appropriate infusion codes and justification for the chosen setting when requesting authorization.

Note

Site-of-service review applies to ages ≥13; pediatric considerations

Site‑of‑service medical necessity review applies for individuals aged 13 years and older; pediatric considerations for younger ages should follow pediatric administration guidance in the policy and may preclude site‑of‑service review.

Note

IV ERT administration setting due to infusion/anaphylaxis risk

IV enzyme replacement therapies are often administered in settings able to manage infusion‑associated reactions and anaphylaxis; document need for monitored infusion center or hospital outpatient setting when risk factors are present.

Note

Vimizim infusion center or controlled setting due to boxed warning

Because Vimizim carries a boxed warning for life‑threatening anaphylaxis, administration in an infusion center or a setting capable of managing anaphylaxis is appropriate; document monitoring and emergency preparedness when requesting site approval.

Note

Infusion-related trial contexts and setting implications

Infusion‑related trial contexts underscore the need for settings that can manage IV administration and complications; include trial‑derived monitoring considerations when requesting hospital outpatient setting for agents studied as IV infusions.

Note

Home administration examples (SC or monthly therapies enabling home use)

Some subcutaneous or monthly therapies (e.g., Rivfloza, vosoritide) enable outpatient or home administration; include documentation of appropriateness for home infusion if requesting home setting.

Note

Alaska fully-insured member exception for site-of-service review

Alaska fully‑insured members are excluded from the SOS site‑of‑service criteria per Alaska HB 226; for these members follow the infusion and injection drug Medical Necessity criteria instead and contact Customer Service if needed.

Note

Zycubo and Forzinity added to pharmacy benefit application (site/benefit implication)

Zycubo and Forzinity have been added to the pharmacy benefit application; verify benefit routing and submit prior authorization via the pharmacy pathway when applicable.

Note

Site of service review introduced/applied to specific drugs effective on noted dates

Site‑of‑service review has been introduced or applied to multiple specific drugs effective on the dates noted in the policy history; check the policy history and coding appendix for effective dates and include site justification when required.

Genetic/enzyme confirmationDiagnosis confirmed by documented enzyme deficiency or genetic testing showing pathogenic mutations (disease‑specific genes)

ExamplesAGXT (PH1), IDUA (MPS I), SMPD1 (ASMD), GAA (Pompe)

UseRequired for prior authorization and ongoing coverage documentation

inv-150: Primary hyperoxaluria type 1 (PH1) definition

PH1 definitionAutosomal recessive disorder due to AGXT (AGT) mutation or enzyme deficiency with elevated urinary and plasma oxalate

Diagnostic thresholdsUOx >=0.7 mmol/24hr/1.73 m2 or POx >=20 µmol/L or age‑specific spot UOx/Cr elevations

Clinical consequenceLeads to nephrolithiasis, nephrocalcinosis, and potential ESKD

inv-151: Acid sphingomyelinase deficiency (ASMD) definition

ASMD definitionChronic neurovisceral or visceral disease confirmed by ASMD enzyme assay and SMPD1 gene sequencing

Severity thresholdAdult DLCO <=70% predicted used as a severity criterion for Xenpozyme eligibility

DocumentationBaseline DLCO required for adults in authorization packet

inv-152: Adjusted body weight for dosing when BMI > 30

Adjusted body weight formulaAdjusted body weight (kg) = (actual height in m)^2 x 30 (use when BMI > 30)

UseApplied to determine maintenance dosing for select weight‑based therapies

ReferencePolicy dosing notes for agents with BMI‑based adjustments

inv-153: 6-minute walk distance test (6MWD) definition

6MWD definitionDistance walked on a flat surface in 6 minutes to evaluate integrated cardiopulmonary and muscular function

Use in trialsCommon functional endpoint for ERTs (e.g., Vimizim, Elaprase) and re‑authorization evidence

InterpretationReported as meters change from baseline in clinical studies

inv-154: 3-minute stair climb test definition

3‑minute stair climb testMeasures total time to ascend/descend steps over 3 minutes to assess functional strength, balance, and agility

Clinical roleUsed as functional endpoint in some neuromuscular/respiratory studies

InterpretationShorter time indicates better performance

inv-155: GL-3 Inclusion Score definition

GL‑3 Inclusion Score definitionHistologic score 0–3 of globotriaosylceramide inclusions in renal interstitial capillary endothelial cells

Scale0 = normal; 3 = severe inclusions

UseReferenced as histologic endpoint in Fabry disease studies

inv-156: CRIM-negative definition (Pompe context)

CRIM‑negative definitionIndividuals lacking cross‑reactive immunologic material (CRIM‑negative) have higher risk of death or invasive ventilation in Pompe context

Diagnostic implicationCRIM status affects immunologic risk with ERT and may guide management

TestingDetermined by protein expression assays or genetic inference

inv-157: XLH definition

XLH definitionHeritable rickets disorder caused by PHEX mutations leading to elevated FGF23, renal phosphate wasting, and impaired bone mineralization

Lab featuresLow serum phosphate, reduced tubular phosphate reabsorption; alkaline phosphatase elevated in children

Treatment goalsImprove pain and bone deformity; avoid overtreatment to limit nephrocalcinosis

inv-159: Mucopolysaccharidosis IVA (MPS IVA, Morquio A) definition

MPS IVA definitionAutosomal recessive GALNS enzyme deficiency causing keratan sulfate and chondroitin‑6‑sulfate accumulation with skeletal dysplasia

Clinical featuresSkeletal dysplasia, respiratory compromise, reduced life expectancy without treatment

TherapyEnzyme replacement (Vimizim) indicated for MPS IVA

inv-168: Pediatric reference ranges for CK (appendix)

Pediatric CK reference ranges (appendix)Age‑ and sex‑specific CK ranges provided (e.g., 0–90 days male 28–300 U/L; 15–18 yrs female 27–140 U/L)

Table referenceSee Appendix Table 1 for complete age/sex bands

ApplicationUse to interpret CK thresholds for LC‑FAOD and triheptanoin eligibility

inv-169: Bardet-Biedl syndrome symptoms (appendix table)

Bardet‑Biedl syndrome symptoms tableAppendix lists primary symptoms (rod‑cone dystrophy, polydactyly, obesity, learning disabilities, hypogonadism in males, renal anomalies) and secondary features

UseReference for clinical phenotype confirmation when applicable

LocationAppendix Table 2 in policy document

Coding update added HCPCS code C9085; annual review updated Oxlumo criteria to require no prior liver or kidney transplant and added prescriber specialty and added site-of-service review for selected drugs.

05/01/23addition_and_update

Added coverage criteria for Skyclarys, Lamzede, Daybue; expanded Livmarli criteria to include younger individuals; added Sucraid quantity limit and updated HCPCS code mappings.

01/01/24addition

Rivfloza (nedosiran) coverage criteria were added for primary hyperoxaluria type 1 (PH1).

02/01/24administrative

Annual review removed several sickle cell therapies from this policy and moved them to a separate sickle cell policy; HCPCS code adjustments made accordingly.

04/01/24coding_update

New HCPCS codes G0138, J1202, and J1203 were added to the policy coding appendix.

07/01/25material_change

Policy updated to indicate Site-of-Service Medical Necessity criteria does not apply to Alaska fully‑insured members; Zycubo and Forzinity were added to pharmacy benefit routing and Barth syndrome coverage criteria were added.

04/01/26material_changeLatest

Oxlumo coverage criteria were updated to remove the kidney transplant exclusion and clarified acceptable elevated plasma oxalate documentation as ≥20 µmol/L; additional drug-specific criteria (e.g., Kygevvi evidence summary and Menkes disease coverage for Zycubo) were added in 2026 updates.

Oxlumo (lumasiran) documentation requirements were updated to broaden acceptable diagnostic confirmation: in addition to AGXT genetic testing, a liver biopsy demonstrating alanine glyoxylate aminotransferase (AGT) deficiency is acceptable. The policy also clarifies biochemical thresholds by accepting elevated plasma oxalate (POx) documented as ≥20 µmol/L (1.76 mg/L) for coverage documentation. Notably, the policy removed the prior exclusion for individuals with a kidney transplant. Ensure submitted documentation includes one of the accepted diagnostic confirmations and reported POx or urinary oxalate values consistent with the policy thresholds.

Nexviazyme (avalglucosidase alfa‑ngpt) quantity/dosing guidance was added in a prior update: for patients weighing <30 kg the maximum prescribed dose is 40 mg/kg every 2 weeks, and for patients ≥30 kg the maximum prescribed dose is 20 mg/kg every 2 weeks. This dosing clarification should be used when reviewing dosing requests and setting quantity limits at authorization.

Site‑of‑service review and coding assignments were applied to specific drugs effective on stated dates in the policy history. The appendix documents that site‑of‑service review was added for agents such as Adakveo, Aldurazyme, Kanuma, Nexviazyme, Mepsevii, Naglazyme, and Xenpozyme on specified effective dates and that HCPCS/J‑code changes (additions or removals) were implemented concurrently. When authorizing or billing for infusion/injectable therapy, verify the effective date of site‑of‑service rules and the correct HCPCS/J‑code for the date of service. Relevant historical coding updates are listed in the appendix.