UnitedHealthcare Commercia l

Medical Policy Update Bulletin: July 2021

In This Issue

Take Note Page InterQual® 2021 Clinical Criteria Release • Abnormal Uterine Bleeding and Uterine Fibroids ...... 4 • Airway Clearance Devices ...... 4 • Articular Cartilage Defect Repairs ...... 4 • Attended Polysomnography for Evaluation of Sleep Disorders ...... 4 • Catheter Ablation for Atrial Fibrillation...... 4 • Continuous Glucose Monitoring and Delivery for Managing Diabetes ...... 4 • Cosmetic and Reconstructive Procedures ...... 4 • Deep Brain and Cortical Stimulation...... 4 • Hysterectomy...... 4 • Implanted Electrical Stimulator for Spinal Cord ...... 4 • Minimally Invasive Procedures for Gastroesophageal Reflux Disease (GERD) and Achalasia...... 4 • Obstructive Sleep Apnea Treatment...... 4 • Orthognathic (Jaw) Surgery...... 4 • Plagiocephaly and Craniosynostosis Treatment ...... 4 • Pneumatic Compression Devices ...... 4 • Rhinoplasty and Other Nasal Surgeries ...... 4 • Surgery of the Hip ...... 4 • Surgical and Ablative Procedures for Venous Insufficiency and Varicose Veins ...... 4 • Temporomandibular Joint Disorders ...... 4 • Total Artificial Disc Replacement for the Spine...... 4 Quarterly CPT® and HCPCS Code Updates • Am ondys 45™ (Casimersen) ...... 5 • Cardiac Event Monitoring ...... 5

Page 1 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

In This Issue

• Evkeeza™ (-Dgnb) ...... 5 • Gonadotropin Releasing Hormone Analogs ...... 5 • Infertility Diagnosis and Treatment...... 5 • Long-Acting Injectable Antiretroviral Agents for HIV ...... 5 • Molecular Oncology Testing for Cancer Diagnosis, Prognosis, and Treatment Decisions ...... 5 • Oncology Clinical Coverage ...... 5 • Oxlumo™ (Lumasiran) ...... 5 • Preimplantation Genetic Testing ...... 5 • Provider Administered Drugs – Site of Care ...... 5 • Rituximab (Riabni™, Rituxan®, Ruxience ®, & Truxima ®) ...... 5 • Transcatheter Heart Value Procedures ...... 5 • Vertebral Body Tethering for Scoliosis ...... 5 Medical Policy Updates Updated • Cardiac Event Monitoring – Effective Jul. 1, 2021 ...... 6 • Carrier Testing for Genetic Diseases – Effective Jul. 1, 2021 ...... 6 • Gastrointestinal Motility Disorders, Diagnosis and Treatment – Effective Jul. 1, 2021 ...... 6 Revised • Obstructive Sleep Apnea Treatment – Effective Jul. 1, 2021 ...... 6 • Occipital Nerve Injections and Ablation (Including Occipital Neuralgia and Headache) – Effective Aug. 1, 2021 ...... 9 • Transcatheter Heart Valve Procedures – Effective Sep. 1, 2021 ...... 9 Medical Benefit Drug Policy Updates New • Intravitreal Corticosteroid Implants – Effective Jul. 1, 2021 ...... 13 Updated • Oncology Medication Clinical Coverage – Effective Jul. 1, 2021 ...... 14 Revised • (Prolia® & Xgeva ®) – Effective Oct. 1, 2021...... 14 • Intravenous Iron Replacement Therapy (Feraheme®, Injectafer®, & Monoferric®) – Effective Jul. 1, 2021...... 15 • Maximum Dosage and Frequency – Effective Jul. 1, 2021...... 20

Page 2 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

In This Issue

• Medical Therapies for Enzyme Deficiencies – Effective Jul. 1, 2021 ...... 22 • Off-Label/Unproven Specialty Drug Treatment – Effective Aug. 1, 2021 ...... 25 • Ophthalmologic Policy: Vascular Endothelial (VEGF) Inhibitors – Effective Jul. 1, 2021...... 27 • Reblozyl® (Luspatercept-Aamt) – Effective Aug. 1, 2021 ...... 31 • Xolair® (Omalizumab) – Effective Aug. 1, 2021 ...... 34 Coverage Determination Guideline Updates Updated • Durable Medical Equipment, Orthotics, Medical Supplies and Repairs/Replacements – Effective Jul. 1, 2021 ...... 36 • Speech Generating Devices – Effective Jul. 1, 2021 ...... 36 Revised • Preventive Care Services – Effective Sep. 1, 2021 ...... 36 Utilization Review Guideline Updates Revised • Provider Administered Drugs – Site of Care – Effective Jul. 1, 2021 ...... 38

Page 3 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Take Note

InterQual® 2021 Clinical Criteria Release Effective July 1, 2021, the following Medical Policies and Coverage Determination Guidelines have been updated to reflect the applicable InterQual® 2021 clinical criteria reference(s):

Policy Title Policy Type Abnormal Uterine Bleeding and Uterine Fibroids Medical Policy Airway Clearance Devices Medical Policy Articular Cartilage Defect Repairs Medical Policy Attended Polysomnography for Evaluation of Sleep Disorders Medical Policy Catheter Ablation for Atrial Fibrillation Medical Policy Continuous Glucose Monitoring and Insulin Delivery for Managing Diabetes Medical Policy Cosmetic and Reconstructive Procedures Coverage Determination Guideline Deep Brain and Cortical Stimulation Medical Policy Hysterectomy Medical Policy Implanted Electrical Stimulator for Spinal Cord Medical Policy Minimally Invasive Procedures for Gastroesophageal Reflux Disease (GERD) and Achalasia Medical Policy Obstructive Sleep Apnea Treatment Medical Policy Orthognathic (Jaw) Surgery Coverage Determination Guideline Plagiocephaly and Craniosynostosis Treatment Medical Policy Pneumatic Compression Devices Medical Policy Rhinoplasty and Other Nasal Surgeries Coverage Determination Guideline Surgery of the Hip Medical Policy Surgical and Ablative Procedures for Venous Insufficiency and Varicose Veins Medical Policy Temporomandibular Joint Disorders Medical Policy Total Artificial Disc Replacement for the Spine Medical Policy

Page 4 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Take Note

Quarterly CPT® and HCPCS Code Updates Effective July 1, 2021, the following Medical Policies, Medical Benefit Drug Policies, and Utilization Review Guidelines have been updated to reflect the quarterly Current Procedural Terminology (CPT®) and Healthcare Common Procedure Coding System (HCPCS) code additions, revisions, and deletions. Refer to the following sources for information on the code updates: • American Medical Association. Current Procedural Terminology: CPT® • Centers for Medicare & Medicaid Services. Healthcare Common Procedure Coding System: HCPCS Level II

Policy Title Policy Type Summary of Changes Amondys 45™ (Casimersen) Medical Benefit Drug Policy • Replaced C9399 with C9075 Cardiac Event Monitoring Medical Policy Implantable Loop Recorder • Added 0650T Evkeeza™ (Evinacumab-Dgnb) Medical Benefit Drug Policy • Replaced C9399 with C9079 Gonadotropin Releasing Hormone Analogs Medical Benefit Drug Policy • Added J1951 Infertility Diagnosis and Treatment Medical Policy • Added 0253U Long-Acting Injectable Antiretroviral Agents for HIV Medical Benefit Drug Policy • Replaced C9399 with C9077 Molecular Oncology Testing for Cancer Diagnosis, Medical Policy • Added 0250U and G0327 Prognosis, and Treatment Decisions Oncology Medication Clinical Coverage Medical Benefit Drug Policy • Added C9078, C9080, J9348, and J9353 Oxlumo™ (Lumasiran) Medical Benefit Drug Policy • Replaced J3490 and J3590 with J0224 • Removed C9074 Preimplantation Genetic Testing Medical Policy • Added 0254U Provider Administered Drugs – Site of Care Utilization Review Guideline • Added C9075 and J0224 Rituximab (Riabni™, Rituxan®, Ruxience®, & Truxima®) Medical Benefit Drug Policy • Replaced J3590 and J9999 with Q5123 Transcatheter Heart Value Procedures Medical Policy • Added 0646T Vertebral Body Tethering for Scoliosis Medical Policy • Added 0656T and 0657T

Page 5 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Policy Updates

Updated Policy Title Effective Date Summary of Changes Cardiac Event Jul. 1, 2021 Coverage Rationale

Monitoring • Replaced reference to “ infiltrated heart disease” with “infiltrative heart disease” Definition • Updated definition of “ Implantable Loop Recorder” Applicable Codes Implantable Loop Recorder • Updated list of applicable CPT codes to reflect quarterly edits; added CPT code 0650T Supporting Information • Updated Clinical Evidence and References sections to reflect the most current information Carrier Testing for Jul. 1, 2021 Definitions Genetic Diseases • Updated definition of “Expanded Carrier Panel Screening” Supporting Information • Updated Description of Services, Clinical Evidence, and References sections to reflect the most current information Gastrointestinal Jul. 1, 2021 Notice of Revision: The following summary of changes has been modified. Revisions to the previous policy update Motility Disorders, announcement are outlined in red below. Please take note of the amended updates to be applied on Jul. 1, 2021. Diagnosis and Treatment Documentation Requirements • Updated list of CPT codes with associated documentation requirements; added 72195, 72196, and 72197 Applicable Codes • Added CPT codes 72195, 72196, and 72197 • Removed CPT code 76498 Supporting Information • Updated Clinical Evidence and References sections to reflect the most current information

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Obstructive Sleep Jul. 1, 2021 Coverage Rationale Nonsurgical Treatment Apnea Treatment Nonsurgical Treatment Removable oral appliances are proven and medically necessary for treating • Revised language pertaining to Obstructive Sleep Apnea (OSA) as documented by a sleep study (e.g., medical necessity clinical coverage polysomnography or Home Sleep Apnea Testing). criteria for removable oral Refer to the Medical Policy titled Attended Polysomnography for Evaluation of appliances: Sleep Disorders for further information.

Page 6 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Obstructive Sleep Jul. 1, 2021 o Added reference to the For many individuals, oral appliance therapy (OAT) may be an effective Apnea Treatment InterQual® 2021, Apr. 2021 alternative to failed continuous positive airway pressure (CPAP) therapy. (continued) Release, CP: Durable Medical Documentation of the following is required: Equipment, Noninvasive • A patient presenting with symptoms of OSA be seen in a face-to-face Airway Assistive Devices evaluation with a qualified physician (MD or DO) trained in sleep medicine

Removed reference to the prior to beginning treatment for OAT (AASM and AADSM, December 2012, o InterQual® 2021, Apr. 2021 AAO-HNS, November 2019)

Release, Medicare: Durable • A treating physician (MD or DO) must diagnose OSA and recommend Medical Equipment, Oral course of treatment (AAO-HNS, November 2019) Appliances for Obstructive • If the patient refuses CPAP therapy, documentation of the refusal from the Sleep Apnea patient’s treating physician (MD or DO) must be supplied Documentation Requirements Updated list of Required Clinical For information on snoring and oral appliances, see the Coverage Determination Guideline titled Durable Medical Equipment, Orthotics, Medical Supplies And Information Repairs/Replacements.

For medical necessity clinical coverage criteria for removable oral appliances, refer to the InterQual® 2021, Apr. 2021 Release, CP: Durable Medical Equipment Noninvasive Airway Assistive Devices.

Click here to view the InterQual® criteria.

The following are unproven and not medically necessary due to insufficient evidence of efficacy:

• Devices for treating positional OSA

• Nasal dilator devices for treating Obstructive Sleep Apnea (OSA) • Removable oral appliances for treating central sleep Apnea • Prefabricated Oral Appliance/Device

Surgical Treatment The following surgical procedures are proven and medically necessary for treating Obstructive Sleep Apnea as documented by polysomnography. For medical necessity clinical coverage criteria, InterQual® Client Defined 2021, CP:

Page 7 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Obstructive Sleep Jul. 1, 2021 Procedures: Apnea Treatment • Mandibular Osteotomy (Custom) - UHG (continued) • Maxillomandibular Osteotomy and Advancement (Custom) - UHG • Uvulopalatopharyngoplasty (UPPP) (Custom) - UHG

Click here to view the InterQual® criteria.

Implantable hypoglossal nerve stimulation is proven and medically necessary in an adult patient with moderate to severe OSA when all of the following criteria are met: • Body Mass Index of (BMI) less than or equal to 32kg/m2; and • Apnea hypopnea Index (AHI) of 15 or greater and less than or equal to 65 as determined with polysomnography; and • Absence of complete concentric collapse at the soft palate level; and • Failure or intolerance of Positive Airway Pressure (PAP) treatments (such as continuous positive airway pressure [CPAP] or bi-level positive airway pressure [BPAP] machines) o PAP failure is defined as an inability to eliminate OSA (AHI of greater than 20 despite PAP usage) and PAP intolerance is defined as: . Inability to use PAP (greater than 5 nights per week of usage; usage defined as greater than 4 hours of use per night); or . Unwillingness to use PAP (for example, a patient returns the PAP system after attempting to use it)

The following surgical procedures are unproven and not medically necessary for treating Obstructive Sleep Apnea due to insufficient evidence of efficacy: • Laser-assisted uvulopalatoplasty (LAUP) • Lingual suspension - Also referred to as tongue stabilization, tongue stitch or tongue fixation • Palatal implants • Radiofrequency ablation of the soft palate and/or tongue base • Transoral robotic surgery (TORS)

Page 8 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Occipital Nerve Aug. 1, 2021 Title Change The following are proven and medically necessary for treating pain due to Injections and Ablation • Previously titled Occipital Neuralgia malignancy involving the head and neck: (Including Occipital and Headache Treatment • Injection of local anesthetics and/or steroids used as occipital nerve blocks Neuralgia and Coverage Rationale • Occipital nerve ablation (destruction by neurolytic agent)

Headache) • Added language to indicate occipital nerve ablation The following are unproven and not medically necessary for diagnosing (destruction by neurolytic agent) is and/or treating occipital neuralgia or headaches, including migraine and proven and medically necessary for Cervicogenic Headaches, due to insufficient evidence of efficacy: treating pain due to malignancy • Injection of local anesthetics and/or steroids, used as occipital nerve blocks involving the head and neck • Neurostimulation or electrical stimulation • Occipital neurectomy Supporting Information • Partial posterior intradural C1-C3 rhizotomy • Updated Clinical Evidence and • Radiofrequency ablation (thermal or pulsed) or denervation References sections to reflect the • Rhizotomy of C1-C3 spinal dorsal roots most current information • Surgical decompression of second cervical nerve root and ganglion Surgical decompression of the greater occipital nerve Transcatheter Heart Sep. 1, 2021 Coverage Rationale Aortic Valve Procedures Aortic Transcatheter aortic heart valve replacement is proven and medically • Revised coverage criteria for necessary when performed according to U.S. Food and Drug Administration transcatheter aortic heart valve (FDA) labeled indications, contraindications, warnings and precautions and replacement; replaced criterion all of the following criteria are met: requiring: • Diagnosis of severe calcific native aortic valve stenosis as indicated by one “Individual does not have a o of the following: bicuspid aortic valve” with o Mean aortic valve gradient ≥40 mmHg; or “individual does not have a o Peak aortic jet velocity ≥4.0 m/s; or congenitally bicuspid aortic 2 o Aortic valve area of ≤ 0.8 cm valve” • Individual is symptomatic (New York Heart Association [NYHA] class II or o “Procedure is performed in a greater) and symptoms are due to aortic valve stenosis center consistent with the • Individual does not have a congenitally bicuspid aortic valve Centers for Medicare and • An interventional cardiologist and an experienced cardiothoracic surgeon Medicaid Services (CMS)” with have determined that the procedure is appropriate “procedure is performed in a • Individual has engaged in a Shared Decision Making conversation with an

center [with] Volume interventional cardiologist and an experienced cardiothoracic surgeon

Page 9 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Transcatheter Heart Sep. 1, 2021 Requirements consistent with • Procedure is performed in a center that meets all of the following criteria: Valve Procedures the Centers for Medicare and o On-site heart valve surgery and interventional cardiology programs; and (continued) Medicaid Services (CMS)” o Post-procedure intensive care unit with personnel experienced in Pulmonary managing individuals who have undergone open-heart valve procedures; and • Added list of valves for Volume Requirements consistent with the Centers for Medicare and transcatheter pulmonary heart o valve replacement: Medicaid Services (CMS)

Proven and Medically Transcatheter valve-in-valve (ViV) replacement within a failed bioprosthetic Necessary aortic valve is proven and medically necessary for individuals at high or Melody™ valve o prohibitive surgical risk (PROM score of ≥8%) when performed according to Sapien valve o FDA labeled indications, contraindications, warnings and precautions. Unproven and Not Medically

Necessary Note: Requests for transcatheter aortic heart valve replacement for low-flow/low-

Harmony™ valve gradient aortic stenosis will be evaluated on a case-by-case basis. o Definitions

• Added definition of “CMS Volume Mitral

Requirements for TAVR” Transcatheter mitral valve repair is proven and medically necessary when

Supporting Information used according to FDA labeled indications, contraindications, warnings and

• Updated Description of Services, precautions in individuals with one of the following clinical indications for Clinical Evidence, FDA, and intervention: References sections to reflect the • Primary (degenerative) mitral regurgitation (MR) when all of the following most current information criteria are met: o Moderate-to-severe or severe MR (grade ≥3); and o Symptomatic NYHA class III or IV; and Prohibitive surgical risk as defined by ONE of the following: o . PROM score of ≥8% for individuals deemed likely to undergo mitral

valve replacement; or

. PROM score of ≥6% for individuals deemed likely to undergo mitral valve repair; or . Predicted risk of death or major morbidity at 1 year of over 50%; and o Care directed by a multidisciplinary heart team which includes a heart

Page 10 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Transcatheter Heart Sep. 1, 2021 failure specialist, interventional cardiologist and cardiothoracic surgeon Valve Procedures experienced in the evaluation and treatment of heart failure and mitral (continued) valve disease. • Secondary (functional) MR when all of the following criteria are met: Moderate-to-severe or severe MR (grade ≥3) with left ventricular ejection o fraction (LVEF) ≥20 and ≤50; and

Symptomatic NYHA class II –IV (ambulatory); and o o Optimal evidence-based management which includes pharmacologic therapy plus cardiac resynchronization therapy as indicated; and

o High surgical risk (PROM score of ≥8%); and o Care directed by a multidisciplinary heart team which includes a heart failure specialist, interventional cardiologist and cardiothoracic surgeon experienced in the evaluation and treatment of heart failure and mitral valve disease.

Pulmonary

Transcatheter pulmonary heart valve replacement, using the Melody™ or

Sapien valves, is proven and medically necessary, when used according to

FDA labeled indications, contraindications, warnings and precautions, in individuals with right ventricular outflow tract (RVOT) dysfunction with one of the following clinical indications for intervention: • Moderate or greater pulmonary regurgitation; and/or • Pulmonary stenosis with a mean RVOT gradient ≥ 35 mmHg

The following transcatheter heart valve devices and/or procedures are unproven and not medically necessary due to insufficient evidence of

efficacy:

• Cerebral protection devices (e.g., Sentinel™)

• Mitral valve repair, reconstruction or replacement, except where noted above • Tricuspid valve repair, reconstruction or replacement • Valve-in-Valve (ViV) replacement within a failed bioprosthesis for mitral, pulmonary, or tricuspid valves

Page 11 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Transcatheter Heart Sep. 1, 2021 • Transcatheter pulmonary heart valve replacement using the Harmony™ valve Valve Procedures (continued)

Page 12 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

New Policy Title Effective Date Coverage Rationale Intravitreal Jul. 1, 2021 This policy provides information about the use of certain specialty pharmacy administered by the intravitreal Corticosteroid route for certain ophthalmologic conditions.

Implants This policy refers to the following intravitreal corticosteroid implant products:

• Iluvien® (fluocinolone acetonide intravitreal implant)

• Ozurdex® ( intravitreal implant)

• Retisert® (fluocinolone acetonide intravitreal implant) • Yutiq® (dexamethasone intravitreal implant)

Iluvien is proven and medically necessary when all of the following criteria are met: • Diagnosis of diabetic (DME); and • Both of the following:

Member has been previously treated with a course of corticosteroids; and o o Member did not have a clinically significant rise in intraocular pressure and

• Prescribed by or in consultation with an ophthalmologist; and

• Dose does not exceed one implant per eye; and • Authorization is for no more than one month.

Ozurdex is proven and medically necessary when all of the following criteria are met: • Diagnosis of one of the following: Macular edema following branch retinal vein occlusion (BRVO); or o Macular edema following central retinal vein occlusion (CRVO); or o Non-infectious uveitis affecting the posterior segment of the eye; or o o Diabetic macular edema (DME) and

• Prescribed by or in consultation with an ophthalmologist; and • Dose does not exceed one implant per eye; and

• Authorization is for no more than one month.

Retisert is proven and medically necessary when all of the following criteria are met: • Diagnosis of chronic non-infectious uveitis affecting the posterior segment of the eye; and • Prescribed by or in consultation with an ophthalmologist; and

Page 13 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

New Policy Title Effective Date Coverage Rationale Intravitreal Jul. 1, 2021 • Dose does not exceed one implant per eye; and Corticosteroid • Authorization is for no more than one month. Implants (continued) Yutiq is proven and medically necessary when all of the following criteria are met: • Diagnosis of chronic non-infectious uveitis affecting the posterior segment of the eye; and • Prescribed by or in consultation with an ophthalmologist; and • Dose does not exceed one implant per eye; and • Authorization is for no more than one month.

Intravitreal corticosteroid Implant products are unproven and not medically necessary for the treatment any other indication due to insufficient evidence of efficacy including, but not limited to the following: • Cystoid macular edema after surgery • Radiation retinopathy

Updated Policy Title Effective Date Summary of Changes Oncology Medication Jul. 1, 2021 Related Policies

Clinical Coverage • Added reference link to the Medical Policy titled Molecular Oncology Testing for Cancer Diagnosis, Prognosis, and Treatment Decisions • Removed reference link to the Medical Benefit Drug Policy titled Lemtrada (Alemtuzumab) Applicable Codes • Updated list of applicable HCPCS codes: o Added C9078, C9080, J9348, and J9353 to reflect quarterly edits o Revised description for J0640, J1950, J9155, J9201, J9202, J9218, and J9316 Supporting Information • Updated Background and References sections to reflect the most current information

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Denosumab (Prolia® Oct. 1, 2021 Template Update This policy refers to the following denosumab products: ® & Xgeva®) • Removed CMS section • Prolia ™ ® • Replaced reference to “MCG Care • Xgeva ® Guidelines” with “InterQual criteria” in Instructions for Use Refer to the policy for complete details.

Page 14 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Denosumab (Prolia® Oct. 1, 2021 Related Policies ® & Xgeva ) • Added reference link to the Utilization Review (continued) Guideline titled Provider Administered Drugs – Site of Care Coverage Rationale • Revised coverage criteria for initial therapy for Prolia (denosumab): o Added criterion to require one of the following: . Both of the following: – History of intolerance to oral bisphosphonate therapy; and – History of failure, contraindication, or intolerance to intravenous bisphosphonate therapy (e.g., pamidronate, zoledronic acid); or . History of failure or contraindication to oral bisphosphonate therapy; or . History of failure, contraindication, or intolerance to IV bisphosphonate therapy o Removed criterion requiring history of failure, contraindication, or intolerance to oral or intravenous bisphosphonate therapy Intravenous Iron Jul. 1, 2021 Template Update This policy refers to the following intravenous iron replacements: ® Replacement • Replaced reference to “MCG™ Care • Feraheme (ferumoxytol) ® ® ® Therapy (Feraheme , Guidelines” with “InterQual criteria” in • Injectafer (ferric carboxymaltose) ® • Monoferric® ()* Injectafer , & Instructions for Use Monoferric®) Coverage Rationale • Added language to indicate Monoferric is not The following intravenous iron replacements are not subject to the

medically necessary for the treatment of any coverage criteria in this section:

Page 15 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Intravenous Iron Jul. 1, 2021 diagnosis addressed within this policy; • Ferrlecit (sodium ferric gluconate complex) Replacement published clinical evidence does not • Infed® (iron dextran) ® ® Therapy (Feraheme , demonstrate superiority in the efficacy and • Venofer () ® Injectafer , & safety of this product to other available Monoferric®) intravenous iron replacement products *Medical Necessity Plans (continued) • Removed language indicating Monoferric is Monoferric is not medically necessary for the treatment of any medically necessary for the treatment of: diagnosis addressed within this policy. o Iron Deficiency (IDA) Without Published clinical evidence does not demonstrate superiority in the Chronic Kidney Disease (CKD) efficacy and safety of this product to other available intravenous iron Iron Deficiency Anemia (IDA) Associated o replacement products. With Chronic Kidney Disease (CKD),

Without End Stage Renal Disease (ESRD) Feraheme (ferumoxytol), Injectafer (ferric carboxymaltose), and

• Revised medical necessity criteria; removed Monoferric (ferric derisomaltose) are proven for the following criterion requiring: indications: Physician attests that in their clinical o opinion, the clinical response would be Iron Deficiency Anemia (IDA) Without Chronic Kidney expected to be superior with Monoferric than experienced with the other products Disease (CKD)

Physician attests that in their clinical Feraheme and Injectafer are medically necessary when the o opinion, the same intolerance, following criteria are met:

contraindication, or severe adverse event • For initial therapy, all of the following: Submission of medical records (e.g., lab values, chart notes, would not be expected to occur with o etc.) supporting the diagnosis of IDA; and Monoferric than experienced with the other products Patient does not have CKD; and o • Removed language pertaining to Monoferric History of failure, contraindication, or intolerance, to oral iron o dosing requirements therapy; and One of the following: o . Both of the following:

– Submission of laboratory values demonstrating

treatment failure after at least 3 weeks of therapy, to

at least two of the following intravenous iron therapies each (Note: Laboratory values should be

obtained within 1 to 3 weeks following the last dose of intravenous iron in a treatment course):

Page 16 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Intravenous Iron Jul. 1, 2021 • Infed® (iron dextran) Replacement • Ferrlecit (sodium ferric gluconate complex) ® ® Therapy (Feraheme , • Venofer (iron sucrose) ® Injectafer , & and Monoferric®) – Physician attests that in their clinical opinion, the

(continued) clinical response would be expected to be superior

with Feraheme or Injectafer than experienced with

the other products or

. Both of the following:

– History of intolerance, contraindication, or severe

adverse event, to all of the following intravenous iron

therapies not previously tried and experienced treatment failure:

• Infed® (iron dextran)

• Ferrlecit (sodium ferric gluconate complex) ® • Venofer (iron sucrose) and

– Physician attests that in their clinical opinion, the

same intolerance, contraindication, or severe adverse

event would not be expected to occur with Feraheme

or Injectafer than experienced with the other

products and

One of the following: o . Feraheme dose does not exceed 510 mg elemental iron per dose and 2.04g elemental iron per course; or

. Injectafer dose does not exceed 750 mg elemental iron

per dose and 1500mg elemental iron per course

and

o Initial authorization will be for no longer than 3 months. • For continuation of therapy, all of the following: o Coverage has previously been provided by UnitedHealthcare

Page 17 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Intravenous Iron Jul. 1, 2021 for Feraheme or Injectafer for the treatment of IDA; and Replacement o Submission of recent laboratory results (within the past 4 ® Therapy (Feraheme , weeks) since the last Feraheme orInjectafer administration to ® Injectafer , & demonstrate need for additional therapy; and Monoferric®) Patient does not have CKD; and o (continued) One of the following: o . Feraheme dose does not exceed 510 mg elemental iron

per dose and 2.04g elemental iron per course; or . Injectafer dose does not exceed 750 mg elemental iron

per dose and 1500mg elemental iron per course; or

and

o Continuation authorization will be for no longer than 3 months.

Iron Deficiency Anemia (IDA) Associated With Chronic

Kidney Disease (CKD), Without End Stage Renal

Disease (ESRD)

Feraheme and Injectafer are medically necessary when the

following criteria are met:

• For initial therapy, all of the following: Diagnosis of IDA and CKD; and o Submission of medical records (e.g., lab values, chart notes, o etc.) supporting the diagnosis of IDA; and

o Patient does not have ESRD; and One of the following: o . Patient’s CKD requires hemodialysis or peritoneal dialysis

treatment; or

. Both of the following:

– Patient’s CKD does not require hemodialysis or

peritoneal dialysis treatment; and – History of failure, contraindication, or intolerance, to oral iron therapy and o One of the following:

Page 18 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Intravenous Iron Jul. 1, 2021 . Both of the following: Replacement – Submission of laboratory values demonstrating ® Therapy (Feraheme , treatment failure after at least 3 weeks of therapy, to ® Injectafer , & at least two of the following intravenous iron Monoferric®) therapies each (Note: Laboratory values should be

(continued) obtained within 1 to 3 weeks following the last dose

of intravenous iron in a treatment course): ® • Infed (iron dextran) • Ferrlecit (sodium ferric gluconate complex)

• Venofer® (iron sucrose)

and

– Physician attests that in their clinical opinion, the

clinical response would be expected to be superior with Feraheme or Injectafer than experienced with

the other products

or

. Both of the following: – History of intolerance, contraindication, or severe

adverse event, to all of the following intravenous iron

therapies not previously tried and experienced

treatment failure: ® • Infed (iron dextran)

• Ferrlecit (sodium ferric gluconate complex) • Venofer® (iron sucrose)

and

– Physician attests that in their clinical opinion, the same intolerance, contraindication, or severe adverse

event would not be expected to occur with Feraheme

orInjectafer than experienced with the other products

and

o One of the following: . Feraheme dose does not exceed 510 mg elemental iron per dose and 2.04g elemental iron per course; or

Page 19 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Intravenous Iron Jul. 1, 2021 . Injectafer dose does not exceed 750 mg elemental iron Replacement per dose and 1500mg elemental iron per course Therapy (Feraheme®, and ® Injectafer , & o Initial authorization will be for no longer than 3 months. Monoferric®) • For continuation of therapy, all of the following: (continued) o Coverage has previously been provided by UnitedHealthcare for Feraheme or Injectafer for the treatment of IDA with CKD; and o Patient does not have ESRD; and o Submission of recent laboratory results (within the past 4 weeks) since the last Feraheme or Injectafer administration to demonstrate need for additional therapy; and o One of the following: . Feraheme dose does not exceed 510 mg elemental iron per dose and 2.04g elemental iron per course; or . Injectafer dose does not exceed 750 mg elemental iron per dose and 1500mg elemental iron per course and o Continuation authorization will be for no longer than 3 months. Maximum Dosage Jul. 1, 2021 Template Update This policy provides information about the maximum dosage per and Frequency • Removed CMS section administration and dosing frequency for certain medications ™ • Replaced reference to “MCG Care administered by a medical professional. Most medications have a ® maximum dosage and frequency based upon body surface area or Guidelines” with “InterQual criteria” in Instructions for Use patient weight or a set maximal dosage and frequency independent of

Coverage Rationale patient body size.

• Revised list of applicable drug products; Drug Products: added: • abatacept (Orencia®) (Eylea®) o • aflibercept (Eylea ®) -dbll (Beovu®) o • (Avastin®) sodium (Macugen®) o • bevacizumab-awwb (Mvasi™) (Lucentis®) o • bevacizumab-bvzr (Zirabev®) • Revised list of drug products with Maximum • brolucizumab-dbll (Beovu®) Allowed Frequencies; added: • certolizumab pegol (Cimzia®)

Page 20 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale ® ® Maximum Dosage Jul. 1, 2021 o Avastin • denosumab (Prolia & Xgeva ) ® and Frequency o Beovu • eculizumab (Soliris ) ® (continued) o Eylea • emicizumab-kxwh (Hemlibra ) ® o Lucentis • golimumab (Simponi Aria ) Macugen • infliximab (Remicade®) o Mvasi • infliximab-axxq (Avsola™) o Zirabev • infliximab-dyyb (Inflectra®) o Supporting Information • infliximab-abda (Renflexis®) ® • Updated References section to reflect the most • nivolumab (Opdivo ) current information • omalizumab (Xolair®) • patisiran (Onpattro®) • pegaptanib sodium (Macugen®) ® • (Neulasta ) ™ • pegfilgrastim-apgf (Nyvepria ) • pegfilgrastim-cbqv (Udenyca®)

• pegfilgrastim-jmdb (Fulphila™)

• pegfilgrastim-bmez (Ziextenzo®)

• ranibizumab (Lucentis®) • ravulizumab-cwvz (Ultomiris®) • rituximab (Rituxan®) • rituximab-pvvr (Ruxience™) ® • rituximab-abbs (Truxima ) ® • rituximab and hyaluronidase (Rituxan Hycela ) • cypionate (Depo-Testosterone®)

• testosterone enanthate

• testosterone pellets (Testopel®)

• testosterone undecanoate (Aveed®) • tildrakizumab-asmn (Ilumya™) • tocilizumab (Actemra®) • (Herceptin®) • trastuzumab-anns (Kanjinti™) • trastuzumab-dkst (Ogivri™) • trastuzumab-dttb (Ontruzant®)

Page 21 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Maximum Dosage Jul. 1, 2021 • trastuzumab-pkrb (Herzuma®) and Frequency • trastuzumab-qyyp (Trazimera™) (continued) • ustekinumab (Stelara®) • vedolizumab (Entyvio®) • zoledronic acid (zoledronic acid, Reclast®, and Zometa ®

The use of medications included in this policy when given within the maximum dosage and/or frequency based upon body surface area or patient weight or a set of maximal dosage and/or frequency independent of patient body size are proven when used according to labeled indications or when otherwise supported by published clinical evidence.

The medications included in this policy when given beyond maximum dosages and/or frequency based upon body surface area or patient weight or a set maximal dosage independent of patient body size are not supported by package labeling or published clinical evidence and are unproven.

Refer to the policy for complete details. Medical Therapies for Jul. 1, 2021 Title Change Nulibry (fosdenopterin) has been added to the Review at Launch Enzyme Deficiencies • Previously titled Enzyme Replacement Therapy program. Some members may not be eligible for coverage of this Template Update medication at this time. Refer to the policy titled Review at Launch for New to Market Medications for additional details. • Removed CMS section ™ • Replaced reference to “MCG Care Guidelines” with “InterQual® criteria” in This policy refers to the following medical therapies for enzyme

Instructions for Use deficiency products: • Aldurazyme® (laronidase) Coverage Rationale • Elaprase® (idursulfase) • Revised list of applicable medical therapies for • ® ™ Fabrazyme (agalsidase beta) enzyme deficiency products; added Nulibry ® • Kanuma (sebelipase alfa) (fosdenopterin) ® • Lumizyme (alglucosidase alfa) • Added language to indicate: ™ • Mepsevii (vestronidase alfa-vjbk)

Page 22 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale ® Medical Therapies for Jul. 1, 2021 o Nulibry (fosdenopterin) has been added to • Naglazyme (galsulfase) Enzyme Deficiencies the Review at Launch program • Nulibry™ (fosdenopterin) ™ (continued) o Some members may not be eligible for • Revcovi (elapegademase-lvlr) ® coverage of this medication at this time; • Vimizim (elosulfase alfa) refer to the Medical Benefit Drug Policy

titled Review at Launch for New to Market Refer to the policy for complete details.

Medications for additional details

o Nulibry (fosdenopterin) is proven for the treatment of molybdenum cofactor deficiency (MoCD) Type A o Nulibry is medically necessary when all of the following additional criteria are met: . For initial therapy, all of the following: – Diagnosis of molybdenum

cofactor deficiency (MoCD) Type

A confirmed by one of the

following: • Documentation of confirmed MOCS1 gene mutation; or • Documentation of onset of clinical and/or laboratory signs and symptoms consistent with MoCD Type A (e.g., seizures, exaggerated

startle response, high-pitched

cry, axial hypotonia, limb hypertonia, feeding difficulties, elevated urinary sulfite and/or S- sulphocysteine (SSC), elevated xanthine in urine or , or low or absent uric acid in the urine or blood)

Page 23 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Medical Therapies for Jul. 1, 2021 within the first 28 days after Enzyme Deficiencies birth (continued) and – Dosing is in accordance with the United States Food and Drug

Administration approved labeling;

and

– Initial authorization will be for no more than 6 months . For continuation of therapy, all of the following: – Patient has previously received treatment with fosdenopterin therapy; and

– Confirmation of MOCS1 gene

mutation; and

– Patient has experienced a positive clinical response to fosdenopterin therapy (e.g., decrease in seizure activity, improvement in feeding/alertness/responsiveness, improvement in gross motor function and/or growth,

decreased urinary sulfite or SSC,

deceased xanthine in urine or

blood, increased uric acid in urine or blood); and – Dosing is in accordance with the United States Food and Drug Administration approved labeling; and – Reauthorization will be for no more than 12 months

Page 24 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Medical Therapies for Jul. 1, 2021 Applicable Codes Enzyme Deficiencies Nulibry (continued) • Added HCPCS codes C9399, J3490, and J3590 • Added ICD-10 diagnosis codes E72.10 and E72.19 Supporting Information • Updated Background, Clinical Evidence, FDA, and References sections to reflect the most current information Off-Label/Unproven Aug. 1, 2021 Template Update Description ™ Specialty Drug • Replaced reference to “MCG Care This policy provides parameters for coverage of off-label and unproven ® Treatment Guidelines” with “InterQual criteria” in indications of FDA-approved medications covered under the medical Instructions for Use benefit for one of the following: Coverage Rationale • Provider administered or supervised injectable specialty drug with • Revised coverage criteria; replaced criterion a corresponding UnitedHealthcare policy that does not address

requiring “clinical indications supported by the requested indication. ™ MCG Care Guidelines, Ambulatory Care” with • Provider administered or supervised injectable specialty drug with “clinical indications supported by InterQual®, a corresponding UnitedHealthcare policy that lists the drug as

Specialty Rx” unproven for the requested indication.

Supporting Information • Provider administered or supervised injectable specialty drug

• Updated Clinical Evidence and References without a UnitedHealthcare drug policy. sections to reflect the most current information This policy does not address coverage for self-administered medications covered under the pharmacy benefit. Refer to pharmacy benefit coverage.

This policy does not address coverage of injectable oncology

medications (including, but not limited to octreotide acetate, leuprolide acetate, leucovorin and levoleucovorin), including therapeutic radiopharmaceuticals, covered under the medical benefit based upon the National Comprehensive Cancer Network (NCCN) Drugs &

Page 25 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Off-Label/Unproven Aug. 1, 2021 Biologics Compendium® (NCCN Compendium®). Refer to the Medical Specialty Drug Benefit Drug Policy titled Oncology Medication Clinical Coverage for Treatment more information. (continued) This policy does not address coverage of vaccines. Refer to the

Medical Benefit Drug Policy titled Vaccines and the Coverage Determination Guideline titled Preventative Care Services for

additional information on vaccines covered as preventive services.

Indications of Coverage

A specialty drug may be determined medically necessary for the requested off-label or unproven indication when all of the criteria are met: • The drug is approved by the U.S. Food and Drug Administration; and • The requested drug has not been excluded from coverage by UnitedHealthcare due to lack of efficacy, clinical benefit, or

administrative program (e.g., exclusion at launch, plan document); and

• One of the following:

o The requested drug is considered “unproven” per UnitedHealthcare drug policy, where applicable

o The indication for the requested drug is not addressed by a UnitedHealthcare drug policy, where applicable o A UnitedHealthcare drug policy does not exist for the requested drug

and

• The requested drug is intended to treat a chronic and seriously

debilitating, or serious rare disease; and

• The patient has not failed a previous course or trial of the requested drug; and • The patient has not been in or is not currently in an eligible ; and

Page 26 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Off-Label/Unproven Aug. 1, 2021 • Documented history of failure, contraindication, or intolerance to Specialty Drug standard, conventional therapies to treat or manage the disease or Treatment condition, where available; and (continued) • Diagnosis is clinically supported as a use by at least one of the following: o One of the following compendia: . The American Hospital Formulary Service Drug Information (AHFS-DI) under the Therapeutic Uses section; or . The Elsevier Gold Standard’s Clinical Pharmacology under the Indications section; or . DRUGDEX System by Micromedex® has a Strength of Recommendation rating of Class I, Class IIa, or Class IIb under the Therapeutic Uses section or ® o Clinical indications supported by InterQual Specialty Rx; or o Two (2) articles from major peer reviewed medical journals that present data supporting the proposed off-label use or uses as generally safe and effective unless there is validated and uncontested contradictory evidence presented in a major peer-reviewed medical journal. (Examples of accepted journals include, but are not limited to, Journal of American Medical Association, New England Journal of Medicine, and Lancet. Accepted study designs may include, but are not limited to, randomized, double blind, placebo controlled clinical trials. Evidence limited to case studies or case series is not sufficient to meet the standard of this criterion.) Ophthalmologic Jul. 1, 2021 Template Update This policy provides information about the use of certain specialty Policy: Vascular • Removed CMS section pharmacy medications administered by the intravitreal route for ™ Endothelial Growth • Replaced reference to “MCG Care ophthalmologic conditions. ® Factor (VEGF) Guidelines” with “InterQual criteria” in This policy refers to the following drug products, all of which are Inhibitors Instructions for Use

Page 27 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Ophthalmologic Jul. 1, 2021 Coverage Rationale vascular endothelial growth factor (VEGF) inhibitors: ® Policy: Vascular • Added language to indicate the following • Avastin (bevacizumab) ® Endothelial Growth General Requirements pertain to medical • Beovu (brolucizumab-dbll) Factor (VEGF) necessity review (applicable to all medical • Eylea® (aflibercept) ® Inhibitors necessity requests): • Lucentis (ranibizumab) ® (continued) For initial therapy, both of the following: • Macugen (pegaptanib) o ™ . Diagnosis; and • Mvasi (bevacizumab-awwb) ® . Intravitreal VEGF inhibitor • Zirabev (bevacizumab-bvzr)

administration is no more than 9 doses “Bevacizumab” will be used to refer to Avastin, Mvasi, & Zirabev. per year per eye, regardless of diagnosis

For continuation of therapy, both of the The following information pertains to medical necessity review: o following:

. Documentation of positive clinical General Requirements (applicable to all medical

response to anti-VEGF therapy; and necessity requests) . Intravitreal VEGF inhibitor • For initial therapy, both of the following: administration is no more than 9 doses o Diagnosis; and per year per eye, regardless of o Intravitreal VEGF inhibitor administration is no more than 9 diagnosis doses per year per eye, regardless of diagnosis. Applicable Codes • For continuation of therapy, both of the following: • Added Maximum Allowed Frequencies for: o Documentation of positive clinical response to anti-VEGF Avastin o therapy; and Mvasi Intravitreal VEGF inhibitor administration is no more than 9 o o Zirabev doses per year per eye, regardless of diagnosis. o Beovu o o Eylea Diagnosis-Specific Requirements Lucentis o The information below indicates the list of proven and medically Macugen o necessary indications.

Beovu (brolucizumab) is proven and medically necessary for the

treatment of: • Neovascular age-related (AMD)

Page 28 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Ophthalmologic Jul. 1, 2021 Bevacizumab is proven and medically necessary for the treatment of: Policy: Vascular • Choroidal neovascularization secondary to pathologic myopia, Endothelial Growth angioid streaks/, or ocular Factor (VEGF) histoplasmosis syndrome (OHS) Inhibitors • Diabetic macular edema (DME)

(continued) • Macular edema secondary to branch retinal vein occlusion

(BRVO) or central retinal vein occlusion (CRVO)

• Neovascular age-related macular degeneration (AMD) • Neovascular glaucoma

• Neovascularization of the iris (NVI) (rubeosis iridis)

• Proliferative

• Type I retinopathy of prematurity

Eylea (aflibercept) is proven and medically necessary for the

treatment of:

• Diabetic macular edema (DME)

• Diabetic retinopathy • Macular edema secondary to branch retinal vein occlusion

(BRVO) or central retinal vein occlusion (CRVO)

• Neovascular age-related macular degeneration (AMD)

Lucentis (ranibizumab) is proven and medically necessary for the

treatment of: • Choroidal neovascularization secondary to pathologic myopia,

angioid streaks/pseudoxanthoma elasticum, or ocular

histoplasmosis syndrome (OHS)

• Diabetic macular edema (DME) • Diabetic retinopathy

• Macular edema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO)

• Neovascular age-related macular degeneration (AMD)

Macugen (pegaptanib) is proven and medically necessary for the

Page 29 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Ophthalmologic Jul. 1, 2021 treatment of: Policy: Vascular • Diabetic macular edema Endothelial Growth • Neovascular age-related macular degeneration (AMD) Factor (VEGF) Inhibitors Additional Information

(continued) Avastin (bevacizumab) is supplied in sterile vials containing a solution

of 25 mg/mL. Doses utilized in ophthalmic conditions generally range

from 6.2 mcg to 2.5 mg. Therefore, bevacizumab in vials is often

divided into single-dose, prefilled syringes for intravitreal use by

compounding pharmacies. Compounding pharmacies must comply with United States Pharmacopeia (USP) Chapter 797, which sets

standards for the compounding, transportation, and storage of

compounded sterile products (CSP). The Pharmacy Compounding

Accreditation Board can verify that the pharmacy is adhering to these

standards.

The American Society of Retinal Specialists (ASRS) is committed to

ensuring that retina specialists have access to compounded drugs

(such as Avastin) that are prepared with high-quality material following good quality controls and sound engineering design by appropriately

trained personnel. Refer to their information page at

https://www.asrs.org/advocacy-practice/access-to-safe-compounded-

agents for resources pertaining to access of safe compounded agents.

Refer to the US Food and Drug Administration (FDA) section of this

policy for information related to contamination of compounded

bevacizumab. In an effort to guard against contamination during the

compounding process, the United States Veterans Health Administration (USVHA) requires that only USVHA pharmacies may

dispense bevacizumab for intravitreal administration to Veterans

Administration beneficiaries. The medication must be dispensed

directly to the VA ophthalmologist, who will then be responsible for

preparing and administering the bevacizumab dose for each patient. In

Page 30 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Ophthalmologic Jul. 1, 2021 addition to strict labeling and storage requirements, the Policy: Vascular ophthalmologist is required to prepare only one dose of medication Endothelial Growth from each vial; if both eyes are to be treated, a separate vial and Factor (VEGF) syringe must be utilized. Inhibitors (continued) Reblozyl® Aug. 1, 2021 Template Update Reblozyl is proven and/or medically necessary for the treatment of (Luspatercept-Aamt) • Removed CMS section anemia in adult patients with beta thalassemia who meet all of the ™ • Replaced reference to “MCG Care following criteria: Guidelines” with “InterQual® criteria” in • Initial Therapy + Instructions for Use o Diagnosis of beta thalassemia including beta thalassemia, 0 Coverage Rationale beta thalassemia, and hemoglobin E/beta thalassemia; and

• Revised coverage criteria for continuation of o Patient is 18 years of age or older; and

therapy for the treatment of symptomatic o Patient is transfusion dependent as evidenced by both of the

anemia in patients with myelodysplastic following in the previous 24 weeks: syndromes or myelodysplastic/ . Has required regular transfusion of at least six units of myeloproliferative neoplasms: packed red blood cells (PRBC); and Added criterion to require the patient has . No transfusion free period greater than 35 days o and experienced a reduction in transfusion Reblozyl is prescribed by, or in consultation with, a requirements while receiving Reblozyl o hematologist, or other specialist with expertise in the documented by one of the following: . A transfusion reduction of at least 4 diagnosis and management of beta thalassemia; and

units of pRBCs per 8 weeks for o Reblozyl dosing is in accordance with the United States Food

patients with a baseline transfusion and Drug Administration (FDA) approved labeling; and

burden of at least 4 units of pRBCs o Initial authorization will be for no more than 6 months. per 8 weeks; or • Continuation of Therapy Diagnosis of beta thalassemia including beta+ thalassemia, . A mean increase of hemoglobin of at o beta0 thalassemia, and hemoglobin E/beta thalassemia; and least 1.5 g/dL for patients with a Reblozyl is prescribed by, or in consultation with, a baseline transfusion burden less than o hematologist, or other specialist with expertise in the 4 units of pRBCs per 8 weeks Removed criterion requiring diagnosis and management of beta thalassemia; and o documentation that the patient no longer o Patient has experienced a reduction in transfusion requirements from pretreatment baseline of at least 2 units

Page 31 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Reblozyl® Aug. 1, 2021 requires pRBC transfusions (transfusion PRBC while receiving Reblozyl; and (Luspatercept-Aamt) independence) o Reblozyl dosing is in accordance with the FDA approved (continued) labeling; and o Reauthorization will be for no more than 12 months.

Reblozyl is proven and/or medically necessary for the treatment of

symptomatic anemia in patients with myelodysplastic syndromes or myelodysplastic /myeloproliferative neoplasms who meet all of the following criteria: • Initial Therapy o One of the following: . Diagnosis of ; . Diagnosis of myelodysplastic/myeloproliferative neoplasm

and

Patient has documented lower risk disease as defined as one o of the following: . Revised International Prognostic Scoring System (IPSS- R): Very Low, Low, Intermediate (Score 0 to ≤ 4.5) . IPSS: Low/Intermediate-1 (Score 0 to 1) . WHO-Based Prognostic Scoring System (WPSS): Very Low, Low, Intermediate (Score 0 to 2) and Documentation of both of the following: o . Hemoglobin <10 g/dL

. Patient requires at least 2 units of packed red blood cells (pRBCs) in the prior 8 weeks. and

o Prescriber has ruled out and/or addressed other causes of anemia (e.g., gastrointestinal bleeding, hemolysis, renal disease, nutritional deficiency, etc.); and

o Documentation of one of the following: . Ring sideroblasts ≥ 15%

Page 32 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Reblozyl® Aug. 1, 2021 . Ring sideroblasts ≥ 5% with an SF3B1 mutation (Luspatercept-Aamt) and (continued) o Documentation of one of the following: . Patient is ineligible for erythropoiesis-stimulating agent (ESA) therapy [e.g., Retacrit (epoetin alfa)] (e.g., serum

>200 mU/mL); or

. Both of the following:

– Serum erythropoietin ≤200 mU/mL – Disease is not responsive or patient is intolerant to ESA [e.g., Retacrit (epoetin alfa)] therapy and o Reblozyl is prescribed by, or in consultation with, a hematologist, oncologist, or other specialist with expertise in the diagnosis and management of myelodysplastic

syndromes; and

Reblozyl dosing is in accordance with the FDA approved o labeling; and

o Initial authorization will be for no more than 3 months. • Continuation of Therapy

o Patient has previously received Reblozyl for the treatment of symptomatic anemia associated with myelodysplastic syndromes or myelodysplastic/myeloproliferative neoplasms; and Patient has experienced a reduction in transfusion o requirements while receiving Reblozyl documented by one of

the following:

o A transfusion reduction of at least 4 units of pRBCs per 8 weeks for patients with a baseline transfusion burden of at least 4 units of pRBCs per 8 weeks; or o A mean increase of hemoglobin of at least 1.5 g/dLfor patients with a baseline transfusion burden less than 4 units of pRBCs per 8 weeks; and o Reblozyl is prescribed by, or in consultation with, a

Page 33 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Reblozyl® Aug. 1, 2021 hematologist, or other specialist with expertise in the (Luspatercept-Aamt) diagnosis and management of myelodysplastic syndromes; (continued) and o Reblozyl dosing is in accordance with the FDA approved labeling; and o Reauthorization will be for no more than 12 months.

Reblozyl is not proven or medically necessary for the treatment of: • Alpha thalassemia • Beta thalassemia in pediatric patients • Myelodysplastic syndromes without ring siderobalsts • Myeloproliferative neoplasm (MPN)-associated myelofibrosis • Non-transfusion dependent beta thalassemia • Sickle beta thalassemia (hemoglobin S [HbS]/beta thalassemia) Xolair® (Omalizumab) Aug. 1, 2021 Template Update This policy refers to Xolair (omalizumab) subcutaneous injection for • Removed CMS section administration by a healthcare professional. Xolair (omalizumab) for ™ • Replaced reference to “MCG Care self-administered subcutaneous injection is obtained under the ® pharmacy benefit. Guidelines” with “InterQual criteria” in Instructions for Use

Refer to the policy for complete details. Coverage Rationale • Added language to indicate this policy refers to

Xolair (omalizumab) subcutaneous injection for administration by a healthcare professional; Xolair (omalizumab) for self-administered subcutaneous injection is obtained under the pharmacy benefit • Replaced language indicating: o “Xolair for subcutaneous use is proven for [the listed indications]” with “Xolair for provider administration is proven for [the

listed indications]”

o “Xolair is medically necessary when all of the [listed] criteria are met” with “Xolair for

Page 34 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Medical Benefit Drug Policy Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Xolair® (Omalizumab) Aug. 1, 2021 provider administration is medically (continued) necessary when all of the [listed] criteria are met” o “Xolair is unproven for [the listed indications]” with “Xolair for provider

administration is unproven for [the listed indications]” • Revised coverage criteria for: Moderate to Severe Persistent Asthma o Replaced criterion requiring “baseline (pre- omalizumab treatment) serum total IgE level greater than or equal to 30 IU/mL and less than or equal to 1500 IU/mL” with “baseline (pre-omalizumab treatment) serum total IgE level greater than or equal to 30 IU/mL and less than or equal to 1300 IU/mL” o Added documentation requirements Chronic Urticaria o Added documentation requirements Nasal Polyps o Added documentation requirements o Added criterion requiring patient is not receiving Xolair in combination with anti- 4 therapy [e.g., Dupixent (dupilumab)] Supporting Information • Updated References section to reflect the most current information

Page 35 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Coverage Determination Guideline Updates

Updated Policy Title Effective Date Summary of Changes Durable Medical Jul. 1, 2021 Coverage Rationale Equipment, Orthotics, Safety Enclosure with Beds Medical Supplies and • Added reference link to the Coverage Determination Guideline titled Beds and Mattresses for additional information

Repairs/Replacements regarding beds Speech Generating Devices • Updated list of examples of a Dedicated Speech Generating Device: o Added Prentke Romich (or PRC) o Replaced “Dynavox” with “Tobii Dynavox” Speech Generating Jul. 1, 2021 Coverage Rationale Devices • Updated list of examples of a Dedicated Speech Generating Device: o Added Prentke Romich (or PRC) o Replaced “Dynavox” with “Tobii Dynavox” Definitions • Added definition of: o Covered Health Care Service(s) o Injury Sickness o Revised Policy Title Effective Date Summary of Changes Coverage Rationale Preventive Care Sep. 1, 2021 Applicable Codes Refer to the policy for complete details. Services Preventive Care Services Screening for Lung Cancer with Low-Dose Computed Tomography • Updated service description: o Removed December 2013 USPSTF “B” rating

Added March 2021 USPSTF o “B” rating to indicate the

USPSTF recommends annual screening for lung cancer with low-dose computed

Page 36 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Coverage Determination Guideline Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Preventive Care Sep. 1, 2021 tomography (LDCT) in adults Services aged 50 to 80 years who have (continued) a 20 pack-year smoking history and currently smoke or have quit within the past 15 years; screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery • Updated preventive benefit instructions; replaced limitations criteria requiring: o “Age 55 to 80 years (ends on 81st birthday)” with “age 50 to 80 years (ends on 81st birthday)” o “At least 30 pack-years of smoking history” with “at least 20 pack-years of smoking history”

Page 37 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Utilization Review Guideline Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Provider Administered Jul. 1, 2021 Related Policies This guideline addresses the criteria for consideration of allowing hospital Drugs – Site of Care • Added reference link to the outpatient facility specialty medication infusion services. This includes claim Medical Benefit Drug Policy titled: submission for hospital-based services with the following CMS/AMA Place of ™ Service codes: o Amondys 45 (Casimersen) Oxlumo™ (Lumasiran) • 19 Off Campus-Outpatient Hospital; and o Coverage Rationale • 22 On Campus-Outpatient Hospital

• Revised list of applicable specialty Alternative sites of care, such as non-hospital outpatient infusion, physician

medications that require healthcare office, ambulatory infusion or home infusion services are well accepted places of

provider administration; added: service for medication infusion therapy. If an individual does not meet criteria for ™ outpatient hospital facility infusion, alternative sites of care may be used. o Amondys 45 (casimersen) ™ o Oxlumo (lumasiran) Outpatient hospital facility-based intravenous medication infusion is Documentation Requirements medically necessary for individuals who meet at least one of the following • Updated list of specialty criteria (submission of medical records is required): medications with associated • Documentation that the individual is medically unstable for administration of documentation requirements: the prescribed medication at the alternative sites of care as determined by Added: o any of the following: . Amondys 45™ The individual’s complex medical status or therapy requires enhanced (casimersen) (HCPCS o monitoring and potential intervention above and beyond the capabilities codes C9075, J3490, and of the office or home infusion setting; or J3590) The individual’s documented history of a significant comorbidity (e.g., . Oxlumo™ (lumasiran) o cardiopulmonary disorder) or fluid overload status that precludes (HCPCS code J0224) treatment at an alternative site of care; or Updated applicable HCPCS o Outpatient treatment in the home or office setting presents a health risk codes for: o due to a clinically significant physical or cognitive impairment; or . Revcovi® (elapegademase- Difficulty establishing and maintaining patent vascular access; or lvlr); added C9399 o To initiate, re-initiate products for a short duration (e.g., 4 weeks) . Tepezza® (- o or trbw); removed J3590 • Documentation (e.g., infusion records, medical records) of episodes of . Viltepso® (viltolarsen); severe or potentially life-threatening adverse events (e.g., anaphylaxis, removed C9399, J3490, seizure, thromboembolism, myocardial infarction, renal failure) that have not and J3590 been responsive to acetaminophen, steroids, diphenhydramine, fluids, . Vyepti™ (- infusion rate reductions, or other pre-medications, thereby increasing risk to jjmr); removed J3590

Page 38 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Utilization Review Guideline Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Provider Administered Jul. 1, 2021 Applicable Codes the individual when administration is in the home or office setting; or Drugs – Site of Care • Updated list of applicable HCPCS • Initial infusion or re-initiation of therapy after more than 6 months; or (continued) codes to reflect quarterly edits; • Homecare or infusion provider has deemed that the individual, home added C9075 and J0224 caregiver, or home environment is not suitable for home infusion therapy (if the prescriber cannot infuse in the office setting). Supporting Information

• Updated References section to Ongoing outpatient hospital facility-based infusion duration of therapy will be reflect the most current information no more than 6 months to allow for reassessment of the individual’s ability to receive therapy at an alternative site of care.

This policy applies to these specialty medications that require healthcare provider administration: • Actemra® (tocilizumab) • Adakveo® (crizanlizumab-tmca) ® • Aldurazyme (laronidase) • Amondys 45™ (casimersen)

• Aralast NP® (A1-PI)

• Avsola™ (infliximab-axxq)

• Benlysta® (belimumab) • Cerezyme® (imiglucerase) • Cimzia® (certolizumab pegol) • Cinqair® (reslizumab) • Crysvita® (-twza) ® • Elaprase (idursulfase) ® • Elelyso (taliglucerase) • Entyvio® (vedolizumab)

• Exondys 51® (eteplirsen)

• Fabrazyme® (agalsidase beta)

• Fasenra® (benralizumab) • Givlaari® (givosiran) • Glassia® (A1-PI) • Ilaris® (canakinumab) • Ilumya™ (tildrakizumab-asmn)

Page 39 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

Utilization Review Guideline Updates

Revised Policy Title Effective Date Summary of Changes Coverage Rationale Provider Administered Jul. 1, 2021 • Inflectra® (infliximab-dyyb) Drugs – Site of Care • Kanuma® (sebelipase alfa) (continued) • Lumizyme® (alglucosidase alfa) • Mepsevii™ (vestronidase alfa-vjbk) • Naglazyme® (galsulfase) • Nucala® (mepolizumab) • Onpattro® (patisiran) • Orencia® (abatacept) • Oxlumo™ (lumasiran) • Prolastin®-C™ (A1-PI) • Radicava® (edaravone) • Reblozyl® (luspatercept-aamt) • Remicade® (infliximab) • Renflexis® (infliximab-abda) • Revcovi® (elapegademase-lvlr) • Simponi Aria® (golimumab) • Soliris® (eculizumab) • Stelara® (ustekinumab) • Tepezza® (teprotumumab-trbw) • Trogarzo® (ibalizumab-uiyk) • Ultomiris® (ravulizumab-cwvz) • Uplizna™ (inebilizumab-cdon) • Viltepso™ (Viltolarsen) • Vimizim® (elosulfase alfa) • VPRIV® (velaglucerase) • Vyepti™ (eptinezumab-jjmr) • Vyondys 53™ (golodirsen) • Zemaira® (A1-PI)

Page 40 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021

General Information

The inclusion of a health service (e.g., test, drug, device or procedure) in this Policy Update Classifications bulletin indicates only that UnitedHealthcare is adopting a new policy and/or New updated, revised, replaced or retired an existing policy; it does not imply that UnitedHealthcare provides coverage for the health service. Note that most New clinical coverage criteria have been adopted for a health service (e.g., test, benefit plan documents exclude from benefit coverage health services identified drug, device or procedure) as investigational or unproven/not medically necessary. Physicians and other health care professionals may not seek or collect payment from a member for Updated services not covered by the applicable benefit plan unless first obtaining the An existing policy has been reviewed and changes have not been made to the member’s written consent, acknowledging that the service is not covered by the clinical coverage criteria; however, items such as the clinical evidence, FDA benefit plan and that they will be billed directly for the service. information, and/or list(s) of applicable codes may have been updated

Note: The absence of a policy does not automatically indicate or imply coverage. Revised As always, coverage for a health service must be determined in accordance with An existing policy has been reviewed and revisions have been made to the the member’s benefit plan and any applicable federal or state regulatory clinical coverage criteria requirements. Additionally, UnitedHealthcare reserves the right to review the clinical evidence supporting the safety and effectiveness of a medical technology prior to rendering a coverage determination. Replaced An existing policy has been replaced with a new or different policy UnitedHealthcare respects the expertise of the physicians, health care professionals, and their staff who participate in our network. Our goal is to Retired support you and your patients in making the most informed decisions regarding The health service(s) addressed in the policy are no longer being managed or the choice of quality and cost-effective care, and to support practice staff with a are considered to be proven/medically necessary and are therefore not simple and predictable administrative experience. The Medical Policy Update excluded as unproven/not medically necessary services, unless coverage Bulletin was developed to share important information regarding guidelines or criteria are otherwise documented in another policy UnitedHealthcare Medical Policy, Medical Benefit Drug Policy, Coverage Determination Guideline, and Utilization Review Guideline updates. When information in this bulletin conflicts with applicable state and/or federal law, UnitedHealthcare follows such applicable federal and/or state law.

The complete library of UnitedHealthcare Medical Policies, Medical Benefit Drug Policies, Coverage Determination Guidelines, and Utilization Review Guidelines is available at UHCprovider.com > Policies and Protocols > Commercial Policies > Medical & Drug Policies and Coverage Determination Guidelines.

Page 41 of 41 UnitedHealthcare Commercial Medical Policy Update Bulletin: July 2021