Prior authorization required; one‑dose lifetime limit

Prior authorization is required for all FDA‑approved gene therapy products; document and obtain prior authorization before administration. The policy imposes a lifetime limit of one dose per lifetime per product unless the FDA label specifies otherwise. Therapies must be administered at a Curative‑designated Center of Excellence or contracted facility with documented gene therapy capability and prescribed by or in consultation with an appropriate disease specialist.

• Prior authorization required for ALL gene therapy products; no exceptions.
• Default lifetime limit: ONE dose per lifetime per product unless FDA label states otherwise.
• Site of care: Curative‑designated Center of Excellence or contracted facility with gene therapy capability.
• Specialist requirement: prescribe by or consult relevant disease specialist (neurologist, hematologist, ophthalmologist, geneticist).

Prior authorization when Luxturna criteria A–E documented

Prior authorization for Luxturna (voretigene neparvovec‑rzyl) requires documentation that all admission/treatment criteria A–E are met for each eye to be treated before authorization is granted.

• Confirmed biallelic RPE65 mutation documented by CLIA‑certified genetic testing.
• Patient is ≥12 months of age.
• Per‑eye retinal viability: OCT posterior pole thickness >100 µm OR ≥3 disc areas without complete atrophy.
• Prescription by an experienced retinal surgeon at a Luxturna‑designated Center of Excellence.
• Treatment limits: one dose per eye per lifetime; bilateral procedures ≥6 days apart.

Prior authorization for Casgevy (J3392) — show eligibility and site

Prior authorization for Casgevy (exagamglogene autotemcel, HCPCS J3392) must show the patient meets diagnosis/genotype, age, disease‑severity, transplant eligibility, and treatment delivery requirements before approval.

• SCD confirmed by molecular/genetic testing with one of the listed genotypes (e.g., HbSS, HbS/β0, HbSC).
• Patient is ≥12 years of age for SCD indications.
• Documentation of disease severity (≥2 VOCs/year ×2 years) or transfusion dependence for TDT.
• No available 10/10 HLA‑matched related donor and no prior allogeneic HSCT or prior gene therapy.
• Treatment to occur at a qualified treatment center (QTC) with BMT capability; HCPCS J3392 and apheresis CPT codes (38205/38206) applicable.

Prior authorization — product‑specific documentation required

Obtain prior authorization and submit product‑specific documentation demonstrating age, diagnosis/genotype, treatment center designation, and one‑time dosing limits for the requested therapy (e.g., Lyfgenia, Zynteglo).

• Lyfgenia: J3394 — document SCD genotype, age ≥12, QTC site, one dose per lifetime, and REMS monitoring plan.
• Zynteglo: bill under J3590/C9399 with evidence of ≥8 RBC transfusions/year and non‑β0/β0 genotype and absence of HLA‑matched sibling donor.
• Ensure administration at product‑designated treatment center per product labeling.

Prior authorization required for Elevidys (J1413) and infusion codes

Prior authorization is required for Elevidys (J‑code J1413) and associated infusion CPT codes; approval is contingent on meeting Elevidys‑specific clinical criteria and site requirements.

• HCPCS J1413 must be authorized before administration.
• Associated infusion CPT codes (96365/96366) and facility revenue coding should be included with the prior authorization request.
• Approval requires meeting Elevidys clinical criteria (DMD genetic confirmation, age, antibody and medical status thresholds) and administration at a designated Sarepta treatment center.

Product‑specific prior authorization — confirm clinical eligibility

Product‑specific prior authorization requires evidence that the patient meets the therapy’s clinical eligibility (e.g., confirmed mutation/genotype, age limits, transfusion history) and acknowledges the one‑dose lifetime limitation.

• Skysona/Zynteglo: document genotype (ABCD1; non‑β0/β0 respectively), MRI/Loes/NFS or transfusion history as applicable.
• Confirm one dose per lifetime and that no disqualifying prior HSCT or gene therapy exists.
• Submit HCPCS/J‑code billing intent (J3590/C9399 or product J‑codes) with clinical documentation.

Preauthorization — coding and billing instructions for gene therapies

Preauthorization required for gene therapies should include billing plans: bill the drug under applicable HCPCS/J‑code (or J3590/C9399 for unclassified biologics) and include relevant procedure codes (e.g., 61720‑61735 for stereotactic neurosurgery) as part of the request.

• Use J3590 or C9399 for unclassified biologics when a product‑specific HCPCS is not available.
• Include procedure CPT codes for the delivery procedure (e.g., stereotactic neurosurgical CPTs 61720‑61735 for Kebilidi).
• Attach anticipated MS‑DRG/revenue code crosswalk if inpatient admission is planned.

Prior authorization for Lenmeldy and Roctavian — confirm lab/genetic eligibility

Prior authorization for Lenmeldy and Roctavian must confirm the therapy‑specific eligibility criteria (genetic confirmation for Lenmeldy; severe hemophilia A laboratory and antibody/inhibitor criteria for Roctavian) and note the single‑dose lifetime limitation.

• Lenmeldy: document biallelic ARSA mutations and appropriate disease stage before authorization.
• Roctavian: document FVIII activity <1 IU/dL, adult male status (≥18), absence of FVIII inhibitors and anti‑AAV5 antibodies, and negative hepatitis B/C and fibrosis assessment.
• Record intention for one‑time dosing and planned post‑infusion hepatic monitoring.

Follow product REMS and payer prior authorization processes when not explicitly listed

Where the document sections do not specify an explicit prior authorization process, follow the product‑specific REMS and Curative payer processes and obtain authorization per usual practice.

• If product section lacks explicit prior authorization instructions, request prior authorization per payer workflow.
• Ensure REMS enrollment and product‑specific monitoring plans are addressed in the authorization submission.

Document prior SMA‑modifying therapy before Zolgensma

If the patient has received prior SMA‑modifying therapy (nusinersen or risdiplam), document prior therapy in the authorization request and clinical record; manage discontinuation timing per clinical judgment around Zolgensma administration.

• Document prior nusinersen (Spinraza) or risdiplam (Evrysdi) exposure.
• Include plan for discontinuation or coordination of prior SMA‑modifying therapy in the treatment plan.

Dose and sequencing requirement — Luxturna (one dose per eye; bilateral ≥6 days)

For Luxturna, document dosing and sequencing: one dose per eye per lifetime and schedule bilateral procedures at least 6 days apart; include this dosing limitation in the prior authorization submission.

• One dose per eye per lifetime.
• If treating both eyes, schedule procedures ≥6 days apart and document in the plan.

Hydroxyurea requirement — document prior response/intolerance or refusal

For Casgevy and Lyfgenia SCD indications, prior authorization requires documentation of inadequate response/intolerance to hydroxyurea, hydroxyurea contraindication, or informed patient refusal when applicable.

• Provide records of hydroxyurea trial and response or intolerance.
• If hydroxyurea declined, include documented informed refusal discussion.

Step therapy note — no step therapy for single‑dose gene therapies

The policy states no step therapy is permitted for single‑dose gene‑replacement or gene‑modifying therapies; these are one‑time treatments administered at designated centers and should be authorized as such.

• No prior step‑therapy sequence required for one‑time gene therapies.
• Ensure authorization reflects one‑time dosing and designated treatment center delivery.

Dose limitation — Hemgenix one dose per lifetime

Hemgenix is limited to a single dose per lifetime; include this dose‑limitation in the authorization and billing documentation.

• Hemgenix dosing: ONE dose per lifetime (2 × 10^13 gc/kg IV infusion).
• No repeat dosing permitted.

Donor availability assessment before autologous HSCT‑based gene therapies

Prior to approving some autologous‑HSCT–based gene therapies (e.g., Skysona, Zynteglo), assess and document availability of an HLA‑matched related donor and preference for standard allo‑HSCT where applicable.

• Document evaluation for an available 10/10 HLA‑matched related donor.
• If a matched donor exists, standard allogeneic HSCT should be considered first per guidelines; include rationale if proceeding with gene therapy.

Step therapy — one‑time dose; no sequential step requirements

Reiterate: no step therapy is specified; gene therapies are one‑time doses per lifetime and authorization must reflect single‑dose administration.

• Authorization must indicate one dose per lifetime for the product requested.
• Do not apply step‑therapy sequencing to these therapies.

Required documentation — CLIA genetic confirmation and baseline labs

Required documentation for any gene therapy authorization must include CLIA‑certified genetic confirmation of the specific causative mutation, relevant laboratory baselines, and disease‑specific data such as SMN2 copy number for SMA where applicable.

• CLIA‑certified genetic test results verifying pathogenic variants for the relevant gene (e.g., SMN1, RPE65, ABCD1, ARSA, DMD, DDC).
• SMN2 copy number for SMA (quantitative assay) when applicable.
• Baseline labs: AST/ALT, platelet count, troponin‑I, CBC, CMP, coagulation studies as requested by product guidance.

Genetic confirmation documentation — Luxturna (CLIA biallelic RPE65)

For Luxturna, genetic confirmation must be documented with CLIA‑certified testing demonstrating biallelic RPE65 pathogenic or likely pathogenic variants (homozygous or two variants in trans).

• Provide CLIA genetic report showing either homozygous RPE65 pathogenic variant or two pathogenic variants in trans (segregation analysis when available).
• Attach clinical diagnosis (e.g., LCA, RP) that aligns with genetic findings.

Ophthalmic and post‑op documentation required for Luxturna

For Luxturna requests, include ophthalmic and postoperative documentation: per‑eye retinal viability (OCT >100 µm in posterior pole OR ≥3 disc areas without complete atrophy), pre/post‑op monitoring plans (IOP, retinal assessment), and scheduled follow‑up including second‑eye timing.

• Per‑eye OCT showing posterior pole thickness >100 µm OR ophthalmoscopy showing ≥3 disc areas without complete atrophy.
• Pre‑treatment corticosteroid plan and postoperative monitoring schedule (including IOP and retinal exams).
• Follow‑up appointment with retinal surgeon within 1 week and plan for second eye ≥6 days after first if bilateral treatment planned.

Prescriber and facility documentation — Luxturna designated surgeon/center

The prescriber must be an experienced retinal surgeon at a Luxturna‑designated Center of Excellence; include facility designation and prescriber credentials in the authorization packet.

• Include the prescribing retinal surgeon’s qualifications and confirmation that the center is a Luxturna‑designated Center of Excellence.
• Document facility capabilities for subretinal injection and postoperative ophthalmic care.

Required clinical documentation — Casgevy/Lyfgenia SCD/TDT requests

For Casgevy and Lyfgenia authorizations, submit molecular/genetic confirmation of SCD/TDT genotype, age eligibility, prior treatment history (including hydroxyurea response/intolerance), transfusion history, absence of available matched donor, and planned BMT‑capable QTC site.

• Molecular/genetic report confirming SCD genotype or TDT genotype.
• For SCD: documentation of ≥2 VOCs per year ×2 years or hydroxyurea intolerance/decline; for TDT: documentation of ≥8 RBC transfusions/year ×2 years.
• Proof of no available 10/10 HLA‑matched related donor and no prior allogeneic HSCT; identify the qualified treatment center (QTC) with BMT capability.

Extended‑stay documentation requirement — justify when goal LOS exceeded

When a planned inpatient stay exceeds the goal length of stay, document the specific medical‑necessity trigger, supporting clinical evidence, and a targeted intervention plan in the record and authorization.

• Document which trigger justifies extended stay (e.g., hepatotoxicity, TMA, engraftment delay, infection).
• Provide clinical data supporting the trigger and the planned interventions to address it.

Diagnostic and antibody documentation — Elevidys (CLIA genetic confirmation and anti‑AAVrh74 titer)

For Elevidys authorization, include CLIA‑certified genetic confirmation of DMD and anti‑AAVrh74 total binding antibody titer results (must be <1:400) as part of the prior authorization package.

• CLIA genetic report confirming DMD gene mutation.
• Anti‑AAVrh74 total binding antibody titer and laboratory method/result demonstrating <1:400.

Required clinical documentation — Hemgenix (FIX activity, antibody/inhibitor, liver plan)

Hemgenix authorizations must include confirmed diagnosis with FIX activity ≤2 IU/dL, antibody/inhibitor testing (no pre‑existing anti‑AAV5 neutralizing antibodies and no FIX inhibitor ≥0.6 BU), hepatitis B/C screening and liver fibrosis assessment, and an outpatient monitoring/discharge plan.

• Laboratory confirmation of FIX activity ≤2 IU/dL by one‑stage or chromogenic assay.
• Anti‑AAV5 neutralizing antibody assessment and documentation of no current/prior FIX inhibitor ≥0.6 BU.
• HBV/HCV screening results and FibroScan or equivalent liver fibrosis assessment.
• Post‑infusion plan: ALT monitoring schedule (weekly ×26 weeks), FIX monitoring, and Hematology follow‑up within 1 week.

Hemgenix discharge documentation — ALT schedule, prophylaxis plan, follow‑up

For Hemgenix discharge, document the ALT monitoring schedule with the Hemophilia Treatment Center, the FIX prophylaxis plan (continue until endogenous FIX production confirmed), and hematology follow‑up within one week.

• ALT monitoring schedule (weekly ×26 weeks) documented and assigned to HTC.
• Document plan for FIX prophylaxis continuation and criteria/monitoring for discontinuation.
• Schedule hematology follow‑up within 1 week of discharge.

Extended stay documentation — document trigger(s), evidence, and intervention plan

When goal length of stay is exceeded for any gene therapy, explicitly document the trigger(s) and supporting clinical evidence; provide a targeted intervention plan to support continued inpatient coverage.

• Identify the specific medical‑necessity trigger(s) causing extended stay.
• Attach clinical data supporting the need for continued inpatient care and a plan for interventions and reassessment.

Required documentation — Zynteglo genotype and transfusion history

For Zynteglo requests, include genotype documentation demonstrating non‑β0/β0 status and transfusion history verifying ≥8 RBC transfusions per year as part of the prior authorization submission.

• Genetic report documenting non‑β0/β0 beta‑globin genotype.
• Transfusion records showing ≥8 RBC transfusions per year (as required).
• Statement confirming no available HLA‑matched sibling donor.

Lenmeldy genetic confirmation required (biallelic ARSA)

Lenmeldy authorization must include CLIA‑confirmed genetic testing showing biallelic ARSA mutations; absence of confirmed biallelic ARSA is a denial trigger.

• Submit genetic testing report confirming biallelic ARSA mutations.
• Do not authorize if ARSA mutation is not genetically confirmed.

Roctavian pre‑infusion documentation — FVIII, inhibitors, antibodies, viral/hepatic status

Roctavian prior authorization must include pre‑infusion documentation: FVIII activity <1 IU/dL, adult male age ≥18, history of prophylactic FVIII use or life‑threatening hemorrhage, absence of FVIII inhibitors, negative anti‑AAV5 antibodies, and negative hepatitis B/C and liver fibrosis assessment.

• FVIII activity result demonstrating <1 IU/dL.
• FVIII inhibitor testing showing absence of current/prior inhibitors (≥0.6 BU).
• Anti‑AAV5 antibody screening result (negative), HBV/HCV screening, and fibrosis assessment.
• Document patient is adult male (≥18) and current prophylaxis or bleeding history.

Denial risk — failure to obtain prior authorization or meet product criteria

Prior authorization must be obtained before gene therapy; requests will be denied if prior authorization is not obtained or if the patient does not meet product‑specific FDA criteria (age, weight, genetic confirmation, facility designation).

• Denials require licensed clinician review.
• Do not proceed with administration without authorization; lack of authorization is grounds for denial.

Denial triggers — Luxturna (missing genetic confirmation, age, retinal viability)

Denials will be issued when product‑specific eligibility requirements are unmet—for Luxturna, examples include absence of CLIA‑confirmed biallelic RPE65 mutation, monoallelic mutation only, patient <12 months, or lack of viable retinal cells in the eye to be treated.

• If RPE65 mutation is not confirmed by CLIA testing, request will be denied.
• Monoallelic RPE65 mutation or patient age <12 months are denial triggers.
• No viable retinal tissue in the target eye or administration at a non‑designated facility will result in denial.

Triggers for denial — Casgevy (unmet genotype, age, VOC/transfusion, donor/HSCT history)

Requests for Casgevy will be denied if required elements are missing or exclusion conditions are present, including patient age <12, unconfirmed SCD genotype, insufficient VOCs/transfusions, available 10/10 HLA‑matched related donor, prior allogeneic HSCT or prior gene therapy, active uncontrolled infection, MDS/active malignancy, significant organ dysfunction, or administration at a non‑qualified Casgevy treatment center.

• Ensure SCD genotype is molecularly confirmed and disease severity (VOCs/transfusions) documented.
• Confirm absence of a 10/10 HLA‑matched related donor and absence of prior HSCT or gene therapy.

Exclusion triggers — Lyfgenia (active MDS/malignancy; refusal of long‑term follow‑up)

Lyfgenia exclusions that will trigger denial/non‑coverage include active MDS or hematologic malignancy and patient unwillingness to comply with the 15‑year long‑term follow‑up requirement.

• Active myelodysplastic syndrome or hematologic malignancy is an exclusion.
• Documented unwillingness to participate in 15‑year REMS long‑term follow‑up is a denial trigger.

Medical‑status denial triggers — Elevidys (active infection, liver or cardiac dysfunction)

For Elevidys, medical‑status denial triggers include active infection, significant liver dysfunction (ALT/AST ≥3× ULN), or active cardiac disease at the time of infusion; these must be absent for authorization.

• No active infection at infusion time.
• No significant liver dysfunction (ALT/AST <3× ULN).
• No clinically significant active cardiac disease per treating physician.

Denial triggers — Elevidys (BMD, anti‑AAVrh74 ≥1:400, prior gene therapy, organ dysfunction)

Elevidys will be denied if the diagnosis is Becker muscular dystrophy, anti‑AAVrh74 antibody titer is ≥1:400, active infection or significant hepatic/cardiac disease is present, prior gene replacement therapy for DMD occurred, or administration is at a non‑designated facility.

• Becker muscular dystrophy diagnosis (G71.02) is excluded.
• Anti‑AAVrh74 titer ≥1:400 is an exclusion/denial trigger.
• Prior gene replacement therapy for DMD or significant organ dysfunction leads to denial.

Lenmeldy denial triggers — missing ARSA confirmation or advanced/late disease

Lenmeldy will be denied if ARSA mutations are not genetically confirmed, for late‑onset/adult MLD, advanced symptomatic disease stages, or if the patient has prior gene therapy or HSCT.

• ARSA genetic confirmation required; absence leads to denial.
• Late‑onset/adult MLD or advanced symptomatic disease are denial triggers.
• Prior gene therapy or HSCT disqualifies the patient.

Roctavian denial triggers — sex/age, inhibitors/antibodies, viral/hepatic exclusions

Roctavian is denied when the patient has hemophilia B, is female, is <18 years old, has current/prior FVIII inhibitor, has anti‑AAV5 antibodies detected, active hepatitis B/C, significant liver disease, or prior gene therapy for hemophilia A.

• Do not authorize Roctavian for females or patients <18 years.
• Positive anti‑AAV5 antibodies or FVIII inhibitors (≥0.6 BU) are exclusionary.
• Active hepatitis B/C or significant liver disease precludes authorization.

Documentation‑trigger requirement — justify extended inpatient stay

Failure to document one or more required medical‑necessity triggers when goal length of stay is exceeded may jeopardize continued inpatient coverage; include the trigger, evidence, and intervention plan in the medical record and authorization.

• When LOS exceeds goal, document at least one medical‑necessity trigger (e.g., hepatotoxicity, TMA, engraftment delay).
• Attach clinical evidence and a targeted intervention plan to support ongoing inpatient coverage.