ModifiedUnitedHealthcarePolicy CSPA2025D0036X

Somatostatin Analogs (for Pennsylvania Only)

Medical benefit drug policy governing coverage of somatostatin analogs for members in Pennsylvania, including indications like acromegaly, Cushing's disease, malignant bowel disease, bleeding gastroesophageal varices, and chemotherapy-/radiation-induced diarrhea.

Policy Summary

PayerUnitedHealthcare

PolicySomatostatin Analogs (for Pennsylvania Only)

Policy CodePolicy CSPA2025D0036X

Change TypeMaterial coverage change — removed proven status for HIV‑AIDS‑related diarrheacode/refs updated

Effective DateMay 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization documenting indication-specific criteria (diagnosis confirmation and prior therapy failure or ineligibility).

SourceLink

POLICY UPDATE CHANGES

Added language to indicate Somatostatin analogs are unproven and not medically necessary for treating HIV-AIDS-related diarrhea.

Removed language indicating Sandostatin (octreotide acetate) and Sandostatin LAR (octreotide acetate LAR) are proven for the treatment of refractory HIV-AIDS-related diarrhea.

Reformatted list of applicable ICD-10 diagnosis codes to reflect/include the corresponding HCPCS codes and removed ICD-10 codes B20 and R19.7.

Updated Clinical Evidence, FDA, and References sections to reflect the most current information.

Pennsylvania-onlystate applicability

Multipleagents named

6unproven indications

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

Coverage Criteria for Somatostatin Analogs

Bleeding gastroesophageal varices

Sandostatin (octreotide acetate) and Sandostatin LAR are proven and medically necessary when BOTH of the following are met:

Bleeding gastroesophageal varices indication: Diagnosis of bleeding esophageal varices associated with liver disease; and octreotide acetate will be used as an adjunct to endoscopic therapy

Symptom control indications

Sandostatin agents are proven for:

Other proven indications: Chemotherapy- and/or radiation-induced diarrhea; malignant bowel disease

Acromegaly — Sandostatin IR

Sandostatin IR is proven and medically necessary for acromegaly when ALL of the following are met:

Acromegaly: diagnostic criteria: Diagnosis of acromegaly; and diagnosis confirmed by either serum GH > 1 ng/mL after a 2-hour OGTT or elevated serum IGF-1 for age/genderGH > 1 ng/mL after 2-hour OGTT

Acromegaly: prior therapy: Inadequate response to surgery, radiotherapy, or dopamine agonist therapy; OR not a candidate for surgery, radiotherapy, or dopamine agonist therapy

Acromegaly — Sandostatin LAR

Sandostatin LAR is proven and medically necessary for acromegaly when ALL of the following are met:

Acromegaly: diagnostic and prior therapy: Diagnosis of acromegaly; diagnosis confirmed by either GH > 1 ng/mL after 2-hour OGTT or elevated IGF-1; and either inadequate response to surgery/radiotherapy/dopamine agonist OR not a candidate for those therapiesGH > 1 ng/mL after 2-hour OGTT

Initial treatment with octreotide IR has been shown to be effective and tolerated

Cushing's disease — pasireotide

Signifor and Signifor LAR (pasireotide) are proven and medically necessary for Cushing's disease when BOTH of the following are met:

Cushing's disease: Diagnosis of Cushing's disease; and inadequate response to pituitary surgery OR not a candidate for pituitary surgery

Acromegaly — Signifor LAR long-acting pasireotide statements

Signifor LAR and other long-acting pasireotide statements for acromegaly require:

Acromegaly: pasireotide LAR: Diagnosis of acromegaly with confirmation by GH > 1 ng/mL after OGTT or elevated IGF-1; and inadequate response to surgery, radiotherapy, or dopamine agonist OR not a candidate for those therapies

Acromegaly — lanreotide (Somatuline) medical necessity criteria

Somatuline (lanreotide) and Lanreotide Injection are proven and medically necessary for acromegaly when ALL of the following are met:

Acromegaly: lanreotide: Diagnosis of acromegaly; diagnosis confirmed by GH > 1 ng/mL after 2-hour OGTT or elevated IGF-1; and either inadequate response to surgery/radiotherapy/dopamine agonist therapy OR not a candidate for those therapiesGH > 1 ng/mL after 2-hour OGTT

General medical necessity and unproven indications

Covered when documentation shows clinical need and alternatives exhausted or contraindicated; some uses are unproven.

Therapy after failed/unsuitable alternatives: Use of a somatostatin analog may be supported when there is inadequate response to or the patient is not a candidate for surgery, radiotherapy, or dopamine agonist therapy (e.g., bromocriptine, cabergoline)

Source lists these as prerequisites or conditions to consider before somatostatin analogs

Unproven/Not Medically Necessary Indications: Use for HIV-AIDS-related diarrhea, pancreatitis, persistent hyperinsulinemic hypoglycemia of infancy, prevention of postoperative pancreatic surgery complications, and short bowel syndrome is unproven and not medically necessary

Requests outside proven indications reviewed case-by-case

Evidence summaries by indication

Evidence by indication — summarize key efficacy and safety findings (trial-level).

Malignant bowel obstruction: Pilot randomized trial (n=64) showed octreotide LAR plus short-term IR octreotide was successful in 38% vs 28% placebo; primary endpoint not met and study underpowered; response higher in patients with Karnofsky >=50.

Small sample, exploratory; tolerability acceptable

Refractory HIV/AIDS-related diarrhea: Prospective open-label study (n=51) showed 41.2% partial/complete response; larger randomized trials mixed with subgroup benefit for very high baseline stool weights.

Limited by small sample size and lack of randomization

Chylothorax (neonates/children/adults): Systematic reviews and case series provide mixed evidence; some case reports/series show resolution while randomized trials are lacking; caution advised.

Variable dosing and duration across reports

Indication-aligned medical necessity

Coverage should be considered when use aligns with FDA indications and guideline-recommended scenarios.

Typical coverage-aligned conditions: Patient has diagnosis consistent with drug indication (acromegaly, Cushing's disease, or GEP-NET/carcinoid syndrome as specified by each product) AND patient is not a surgical candidate or has inadequate response to surgery/radiotherapy when required by the product label

See individual drug indications in supporting chunks

Coverage by indication

Covered when aligned with FDA indications and plan medical necessity criteria:

Acromegaly indication: Long-term treatment of acromegalic patients who had inadequate response to or cannot be treated with surgery and/or radiotherapy (Somatuline Depot, Lanreotide Injection).

Supported by prescribing information.

GEP-NETs indication: Treatment of adult patients with unresectable, well- or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival (Somatuline Depot, Lanreotide Injection).

Supported by prescribing information.

Carcinoid syndrome indication: Treatment of adults with carcinoid syndrome to reduce frequency of short-acting somatostatin analogue rescue therapy (Somatuline Depot).

Supported by prescribing information.

Requests for somatostatin analogs for the conditions listed below are considered unproven and not medically necessary and may be denied: HIV-AIDS-related diarrhea, pancreatitis, persistent hyperinsulinemic hypoglycemia of infancy, prevention of postoperative complications following pancreatic surgery, and short bowel syndrome. Uses not identified as proven in this policy are considered unproven due to insufficient peer-reviewed evidence and will be reviewed on a case-by-case basis.

Somatostatin analogs are considered unproven and not medically necessary for the conditions listed in this policy (see exclusions). FDA approval or product labeling is provided for informational context only and does not by itself establish coverage for uses that lack adequate supporting evidence.

A Cochrane review of octreotide for neonatal congenital or acquired chylothorax found no randomized controlled trials and concluded that no practice recommendation could be made from the identified evidence. Published reports are limited to case reports and small series with variable dosing and outcomes; randomized trials or prospective registry data are needed to establish safety and efficacy.

Information on U.S. Food and Drug Administration approvals is included in the policy for reference; however, FDA approval alone is not a basis for coverage under this policy and coverage decisions require alignment with the policy's clinical criteria.

Policy revision effective 05/01/2025 explicitly removed prior language listing octreotide as proven for refractory HIV-AIDS-related diarrhea and now states that somatostatin analogs are unproven and not medically necessary for HIV‑AIDS‑related diarrhea.

When considering somatostatin analog therapy for indications not specified as proven, clinicians and reviewers should treat such uses as unproven; documentation of rationale and supporting evidence will be required and requests will be evaluated on a case‑by‑case basis with a high risk of noncoverage if robust clinical data are absent.

The policy lists specific conditions for which somatostatin analogs are unproven and not medically necessary. Requests for these indications may be denied and should include compelling clinical justification and supporting literature if submitted for case‑by‑case review.

Current literature does not support routine prophylactic use of somatostatin or octreotide to prevent post‑ERCP pancreatitis. Larger prospective trials found octreotide ineffective for ERCP prophylaxis, and meta-analyses have reported mixed results; routine prophylactic administration is therefore not supported by the evidence.

Systematic reviews and a large randomized trial do not support the routine use of somatostatin/octreotide as standard management for acute pancreatitis. Evidence has not demonstrated improvement in mortality, organ failure, or other key clinical outcomes to justify routine use in acute pancreatitis.

The coverage rationale was revised effective 05/01/2025 to remove prior statements that supported octreotide for refractory HIV‑AIDS‑related diarrhea; the policy now designates somatostatin analogs as unproven and not medically necessary for that indication.

Coding — HCPCS and ICD-10 Mapping

Applicable HCPCS J-codesHCPCS

J1930	Injection, lanreotide, 1 mg.
J1932	Injection, lanreotide, (cipla), 1 mg.
J2353	Injection, octreotide, depot form for intramuscular injection, 1 mg.
J2354	Injection, octreotide, non-depot form for subcutaneous or intravenous injection, 25 mcg.
J2502	Injection, pasireotide long acting, 1 mg

Applicable ICD-10 diagnosis codes (mapped to J-codes in tables)ICD-10

C7A.010	Malignant carcinoid tumor of the duodenum
C7A.011	Malignant carcinoid tumor of the jejunum
C7A.012	Malignant carcinoid tumor of the ileum
C7A.019	Malignant carcinoid tumor of the small intestine, unspecified portion
C7A.020	Malignant carcinoid tumor of the appendix
C7A.021	Malignant carcinoid tumor of the cecum
C7A.022	Malignant carcinoid tumor of the ascending colon
C7A.024	Malignant carcinoid tumor of the descending colon
C7A.025	Malignant carcinoid tumor of the sigmoid colon
C7A.026	Malignant carcinoid tumor of the rectum

1–10 of 55

1/6

Applicable diagnosis/HCPCS mapping (reformatted per revision)mixed

No codes listed

inv-25: GH after OGTT diagnostic threshold — > 1 ng/mL

GH after 2-hour OGTT> 1 ng/mL

IGF-1 confirmationElevated serum IGF-1 above age- and gender-adjusted normal range

Source clinical statementsUsed as diagnostic confirmation for acromegaly in Sandostatin, Sandostatin LAR, Somatuline Depot, and Lanreotide Injection criteria

inv-26: Karnofsky performance status subgroup note from malignant bowel obstruction trial

Karnofsky subgroup findingResponse rate higher among patients with Karnofsky score ≥ 50 (60% vs 28% in trial subgroup)

Trial context

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for somatostatin analogs (including octreotide, lanreotide, and pasireotide) under this policy. Providers must submit a prior authorization request demonstrating that the requested therapy meets indication-specific medical necessity criteria (diagnosis confirmation, prior therapy steps or documented ineligibility, and relevant laboratory or imaging results).

Prior authorization required for somatostatin analogs (octreotide, lanreotide, pasireotide).
Request must include indication-specific documentation (see items below).

Billing Rule

J‑Code and Diagnosis Mapping Required

Claims and prior authorization requests must include the applicable HCPCS/J-code for the product and the mapped diagnosis code(s) as listed in the Applicable Codes section. When submitting a request, ensure the J-code used on the claim corresponds to the diagnosis mapping in the policy.

Initial Therapy and Initiation Requirements

IR trial requirement

Requirement before some long-acting agents

IR trial: Initial treatment with octreotide immediate release (IR) has been shown to be effective and tolerated before using long-acting formulations (Sandostatin LAR).

Requirements for initiating long-acting formulations

Long-acting formulations indicated after successful and tolerated trial of immediate-release formulation.

LAR initiation requirement: Sandostatin LAR and Signifor LAR are indicated in patients in whom initial treatment with the immediate-release injection has been shown to be effective and tolerated

LAR formulations require prior successful IR therapy

pasireotide initiation

In trials of pasireotide LAR for inadequately controlled acromegaly:

Continuation and Renewal Criteria

pasireotide continuation

Long-term continuation data for pasireotide in Cushing's disease:

Long-term pasireotide (Cushing's): Patients with clinical benefit or urinary free cortisol at/below upper limit could continue; 5-year data show sustained reductions in urinary free cortisol and persistent hyperglycemia-related adverse events.

Continuation therapy

Registry and long-term trial data supporting continued therapy when patients achieve biochemical targets and tolerate therapy.

Continuation criteria: Patient achieved and maintains target IGF-1 and/or GH levels (trial targets varied: IGF-1 < ULN; GH ≤ 2.5 µg/L or <1.0 µg/L) and tolerates treatment without unacceptable adverse eventsIGF-1 < ULN; GH ≤2.5 µg/L or <1.0 µg/L

Supported by SODA registry and lanreotide trials

Step Therapy and Sequencing

Step	Requirement	Documentation required
1
Document prior therapies attempted or why they are not applicable before authorizing a somatostatin analog (e.g., surgery, radiotherapy, dopamine agonist therapy).
Clinical notes specifying prior treatments tried (surgery, radiotherapy, bromocriptine/cabergoline) with dates and outcomes, or rationale for ineligibility (medical contraindication, not a surgical candidate).

Step	When step to pasireotide LAR is supported	Supporting trial evidence
1
Consider stepping to pasireotide LAR for patients inadequately controlled on octreotide or lanreotide monotherapy despite ≥6 months of prior SSA therapy.
PAOLA (Gadelha) randomized phase 3 trial: patients inadequately controlled on octreotide LAR 30 mg or lanreotide 120 mg monotherapy ≥6 months randomized to pasireotide LAR 40 mg or 60 mg vs continued octreotide/lanreotide; pasireotide groups achieved biochemical control at 24 weeks (15% and 20%) vs 0% in active control. Additional trials (Colao) showed higher IGF-1 normalization with pasireotide LAR vs octreotide LAR (38.6% vs 23.6%) but higher hyperglycemia rates.

Step	Recommended sequencing/options for inadequate responders	Rationale / evidence
1
For patients with inadequate biochemical response to SRL monotherapy, consider adding pegvisomant or a dopamine agonist (e.g., cabergoline); pasireotide (including LAR) may be effective for some patients uncontrolled on octreotide/lanreotide.
Guideline and study-based guidance: combination SRL plus pegvisomant is efficacious and cost‑effective; several studies report pasireotide LAR efficacy for patients uncontrolled on octreotide/lanreotide but with high rates of treatment‑induced hyperglycemia requiring monitoring and management.

Step	Utilization management tool	Action for provider
1
Follow UnitedHealthcare standard utilization management tools (prior authorization, and third‑party tools such as InterQual) as applicable per plan.
Verify federal/state/contractual benefit requirements, submit required prior authorization documentation per plan processes, and use InterQual criteria where indicated.

Site of Care and Administration Setting

Billing Rule

State administration route and intended site‑of‑care per formulation

Administration route and site‑of‑care must be stated: LAR IM depot injections, deep subcutaneous lanreotide injections, subcutaneous/IV immediate‑release octreotide, or IV infusions — setting may be home, office, infusion center, or hospital outpatient depending on formulation and payer/site‑of‑care rules.

Specify the formulation and planned administration site on the PA (e.g., Signifor LAR IM every 28 days in outpatient clinic).
Ensure billing and site‑of‑care align with J‑code and plan requirements.

Definitions and Drug Descriptions

inv-52: Acromegaly diagnostic confirmation — OGTT and IGF-1 criteria

OGTT/GH diagnostic criterionSerum GH level > 1 ng/mL after a 2-hour oral glucose tolerance test (OGTT)

IGF-1 diagnostic criterionElevated serum IGF-1 above age- and gender-adjusted normal range

Applies toUsed to confirm acromegaly in Sandostatin/Sandostatin LAR, Somatuline Depot, and Lanreotide Injection coverage criteria

inv-53: Sandostatin / Sandostatin LAR / octreotide — drug description and formulations

Generic drug descriptionOctreotide acetate, cyclic octapeptide somatostatin analogue that inhibits GH, glucagon, insulin and several GI hormones

FormulationsImmediate-release (subcutaneous or IV) and long-acting LAR (intramuscular, every 4 weeks)

Background and Clinical Context

Somatostatin analogs (octreotide, lanreotide, pasireotide) are synthetic peptide hormones that mimic somatostatin to inhibit secretion of multiple endocrine and exocrine hormones. They are used to control hormone-secreting tumors (e.g., acromegaly), reduce biochemical markers (GH, IGF‑1, urinary free cortisol), and manage selected symptom syndromes such as carcinoid-related diarrhea or symptoms of malignant bowel obstruction. Long‑acting depot formulations (e.g., Sandostatin LAR, Somatuline Depot, Signifor LAR) provide sustained receptor activation and are generally used after an initial, tolerated trial of immediate‑release formulations.

References, Clinical Evidence, and Revision History

05/01/2025policy_revisionLatest

Policy revised to state somatostatin analogs are unproven and not medically necessary for treating HIV-AIDS-related diarrhea; prior wording that Sandostatin (octreotide) and Sandostatin LAR were proven for refractory HIV/AIDS-related diarrhea was removed.

The Clinical Evidence, FDA, and References sections of this policy were updated to reflect current literature and prescribing information. See the References section for cited systematic reviews, randomized trials, registries, and product prescribing information supporting the policy rationale and revisions.

Policy Summary

PayerUnitedHealthcare

PolicySomatostatin Analogs (for Pennsylvania Only)

Policy CodePolicy CSPA2025D0036X

Change TypeMaterial coverage change — removed proven status for HIV‑AIDS‑related diarrheacode/refs updated

Effective DateMay 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization documenting indication-specific criteria (diagnosis confirmation and prior therapy failure or ineligibility).

SourceLink

On This Page

Dumping syndrome: Short-term symptom control effective; long-term effectiveness limited by side effects and loss of efficacy in many patients.

High discontinuation rates due to side effects or loss of efficacy

Prevention of post-ERCP pancreatitis: Meta-analyses suggest somatostatin may reduce post-ERCP pancreatitis in certain high-dose or infusion regimens; octreotide evidence mixed with some analyses suggesting effectiveness at total doses >= 0.5 mg.octreotide total dose >= 0.5 mg associated with benefit in some analyses

Heterogeneous studies; optimal route and timing uncertain

Acute pancreatitis treatment: Systematic review shows octreotide may reduce serious adverse events and organ failure but not short-term mortality; evidence mixed and not definitive for routine recommendation.

Dosing and administration varied across studies

Postoperative pancreatic surgery (prevention of pancreatic fistula): Trials and meta-analyses conflict: some meta-analyses show reduced pancreatic fistula incidence with perioperative octreotide; others and some trials show no significant benefit. Routine use recommended in pancreatic resection for malignancy per Cochrane but not universally for other indications.

Evidence heterogeneous; duct size influences fistula risk

Short bowel syndrome: Small open-label study (n=8) showed increased small bowel transit time with octreotide depot but no consistent benefits on weight, stool, or absorption parameters; further study needed.

Insufficient evidence for routine use

Persistent hyperinsulinemic hypoglycemia of infancy: Long-term experience limited; concerns include potential growth suppression; place in therapy and dosing not well established.

Insufficient long-term data

Pasireotide and pasireotide LAR (Cushing's disease and acromegaly): Pasireotide shows durable reductions in urinary free cortisol in Cushing's disease and superior biochemical control versus octreotide/lanreotide in acromegaly trials; however, pasireotide/pasireotide LAR is associated with high rates of hyperglycemia-related adverse events and often requires glucose-lowering therapy.

Monitor glucose and HbA1c; document prior therapies for step/authorization decisions

HIV/AIDS-related diarrhea:

Use of somatostatin analogs for HIV-AIDS-related diarrhea is considered unproven and not medically necessary as of the 05/01/2025 policy revision.

Previously listed as proven but removed; policy now states unproven/not medically necessary.

Finding reported in randomized pilot study of octreotide LAR plus IR octreotide for malignant bowel obstruction (n=64)

ImplicationKarnofsky ≥50 associated with greater clinical response in this study; may inform patient selection or expectation setting

inv-27: octreotide total dosage associated with prevention of post-ERCP pancreatitis

Octreotide total dose associated with PEP prevention>= 0.5 mg total

Evidence baseMeta-analyses divided trials by total octreotide dose and concluded effectiveness at ≥ 0.5 mg

LimitationsOptimal route and timing remain uncertain despite dose-related signal

inv-28: GH threshold definitions used in trials (multiple trial-specific thresholds)

Trial biochemical GH thresholdsMean GH < 2.5 µg/L used as biochemical control in multiple trials (e.g., PAOLA, lanreotide studies)

Lower GH targetGH < 1.0 µg/L reported as an outcome in registry and lanreotide studies

Alternative phrasingSome trials report GH ≤ 2.5 µg/L or mean GH concentration <2.5 µg/L paired with normalized IGF-1

ContextDefinitions vary by trial but commonly combine GH threshold with normalized age-adjusted IGF-1

inv-29: (placeholder)

PlaceholderNo data provided in brief or source for this inventory item

ActionNo operational threshold or definition available; item reserved for future content

NoteThis empty/placeholder entry corresponds to an inventory item with no label or summary

J2353, J2354 (octreotide forms); J1930, J1932 (lanreotide); J2502 (pasireotide LAR).
Include the policy-mapped ICD-10 diagnosis code(s) with the J-code on the request/claim.

Prior Authorization

Pasireotide LAR (Signifor LAR) — Prior Authorization Considerations

Prior authorization for pasireotide LAR in acromegaly requires documentation of diagnosis confirmation and prior therapy history; consider trial data and adverse event profile (notably hyperglycemia) when requesting coverage.

Provide biochemical confirmation of acromegaly (OGTT and/or IGF-1) and prior treatment history.
Document prior use and inadequate response to octreotide or lanreotide when applicable (see step therapy item).
Include baseline glycemic parameters and plan for monitoring/manage hyperglycemia.

Denial Risk

Indication‑Aligned Prior Authorization and Denial Risk

Prescriptions should align with FDA-indicated uses and the policy's proven-medically-necessary criteria. Requests for unproven or not medically necessary indications (e.g., HIV‑AIDS‑related diarrhea) have increased risk of denial.

Coverage consideration will prioritize requests that match product indications and documented prior therapy steps (e.g., surgery ineligible or inadequate response to surgery/radiotherapy when required).
Requests for indications listed as unproven/not medically necessary (including HIV‑AIDS‑related diarrhea, pancreatitis, persistent hyperinsulinemic hypoglycemia of infancy, prevention of postoperative complications following pancreatic surgery, short bowel syndrome) are likely to be denied.

Documentation Required

Trial Discontinuation and Limited/Exploratory Efficacy — Provide Context

Document trial discontinuation reasons and acknowledge where evidence is limited. For certain indications (e.g., malignant bowel obstruction) clinical trial data showed limited definitive efficacy and notable trial discontinuations; include these context details if relevant to the request.

If therapy was discontinued, provide reason (e.g., lack of efficacy, adverse events, death) and supporting clinical notes.
When relying on limited or exploratory evidence, attach study reports or summaries to support medical necessity.

Note

Authorization Triggers and Review Process

There are no explicit automatic authorization-denial triggers embedded in the policy; FDA indications are informational and case-by-case review may apply. However, lack of supporting documentation or requests for unproven indications increase denial likelihood.

Policy does not specify prescriptive denial triggers; completeness and clinical appropriateness of submitted documentation drive determinations.
Requests will be reviewed against the policy criteria and applicable benefit plan terms.

Documentation Required

Acromegaly Diagnostic and Prior‑Therapy Documentation

Acromegaly prior-authorization requests must include diagnostic confirmation and prior-therapy documentation: OGTT result, IGF‑1 relative to age/gender norms, prior pituitary surgery and/or radiotherapy details, and documentation of ineligibility for or inadequate response to alternative therapies when required.

Serum GH > 1 ng/mL after a 2-hour OGTT and/or elevated IGF‑1 (age/gender adjusted) at time of diagnosis.
Details of prior pituitary surgery (date, extent, outcome) and radiotherapy (dates, doses).
If step requirements apply, documentation of inadequate response to or ineligibility for surgery, radiotherapy, or dopamine agonists (e.g., bromocriptine, cabergoline).

Billing Rule

Coding and Diagnosis Documentation Required

Provide coding and diagnosis documentation on the prior authorization request and the claim: include the HCPCS/J-code for the drug and the mapped ICD-10 diagnosis code(s) per the policy's Applicable Codes section.

Ensure the selected J-code matches the drug formulation and dose being requested.
Include corresponding ICD-10 diagnosis codes that map to the J-code per the policy (see Applicable Codes).

Documentation Required

Biochemical Monitoring and Adverse Event Documentation

Provide baseline and follow-up biochemical monitoring and adverse event documentation for agents with known safety concerns (e.g., pasireotide-associated hyperglycemia). Include lab values, monitoring schedule, and management plans.

Baseline and serial IGF‑1 and GH measurements for acromegaly patients.
Baseline fasting glucose and/or HbA1c and follow-up glycemic monitoring when using pasireotide; document any glucose-lowering therapy initiation.
Document other relevant labs or imaging (e.g., tumor size changes on MRI, liver function tests) and adverse events.

Documentation Required

Suggested Supporting Clinical Documentation

Suggested supporting clinical documentation to attach to the prior authorization request includes relevant study data, registry results, serial lab values, imaging reports, prior medication trial details, and specialist notes to substantiate medical necessity.

Study/registry excerpts supporting the requested indication (e.g., PAOLA trial, SODA registry) when used to justify treatment choice.
Serial IGF‑1/GH lab results, OGTT results, MRI pituitary reports, and endocrinology consult notes.
Documentation of prior therapy doses/durations and reasons for discontinuation or inadequate response.

Note

Benefit Plan Verification Required

Verify the member's benefit plan, as federal, state, or contractual benefit plan requirements may supersede this policy. Confirm coverage details, prior authorization processes, and any plan-specific restrictions before submitting requests.

Check federal, state, or contractual benefit plan terms which govern coverage determinations.
Confirm whether third‑party utilization management tools (e.g., InterQual) or plan-specific criteria apply.

Step Therapy

Step Therapy and Sequencing Requirements

Document step‑therapy requirements and sequencing: provide evidence of inadequate response to or ineligibility for alternatives (surgery, radiotherapy, dopamine agonists) when required. For conversion to long‑acting formulations, document initial tolerance/efficacy of immediate‑release octreotide when policy requires an IR trial before LAR.

If policy requires a step from octreotide/lanreotide to pasireotide, include documentation of prior use and lack of adequate control (dates, doses, lab/imaging results).
When an IR trial is required prior to LAR, include notes showing effective and tolerated use of octreotide IR.

Step Therapy

Guideline‑Informed Sequencing — Support Clinical Rationale

Guideline‑informed sequencing should be reflected in the clinical rationale submitted: somatostatin analogues or pegvisomant are reasonable initial adjuvant medical therapies per specialty guidelines, with addition of pegvisomant or cabergoline for inadequate responses and careful patient selection for pasireotide given hyperglycemia risk.

Reference Endocrine Society and Pituitary Society recommendations when applicable to support therapy sequencing.
Document rationale for selecting pasireotide versus alternative somatostatin analogues or combination therapy.

pasireotide LAR initiation after prior SSA: PAOLA trial enrolled patients inadequately controlled on octreotide/lanreotide monotherapy for ≥6 months and randomized to pasireotide LAR or continued SSA; pasireotide showed superior biochemical control compared with continued SSA

Prior inadequate control on octreotide/lanreotide was an enrollment criterion

Initial therapy

Guideline-based initial therapy considerations.

Initial medical therapy options: Somatostatin analogues (e.g., octreotide, lanreotide) or pegvisomant considered as initial adjuvant medical therapy for significant disease; choice individualized based on patient factors

Endocrine Society and Pituitary Society guidance

Clinical roleUsed for acromegaly, carcinoid syndrome, chemotherapy-/radiation-induced diarrhea, and adjunctive control of bleeding varices

inv-54: Signifor / Signifor LAR / pasireotide — drug description

Generic drug descriptionPasireotide, a somatostatin analogue binding multiple SSTR subtypes (including SSTR5) that inhibits ACTH secretion

FormulationsShort-acting subcutaneous formulation and long-acting release (Signifor LAR) for intramuscular administration

Clinical roleApproved and used for Cushing's disease and for acromegaly in selected patients per label

inv-55: Somatuline Depot / lanreotide — drug description

Generic drug descriptionLanreotide, a synthetic octapeptide somatostatin analogue with biological activity similar to somatostatin

FormulationsProlonged-release formulations for deep subcutaneous injection (Somatuline Depot, Lanreotide Injection) given every 4 weeks

Clinical roleReduces GH and IGF-1 in acromegaly; indicated for acromegaly and GEP‑NETs per label

inv-56: biochemical control (acromegaly) definition used in trials

Primary trial definitionBiochemical control commonly defined as mean GH concentration < 2.5 µg/L plus normalized age-adjusted IGF-1

Alternate GH thresholdsTrials/reporting also use GH ≤ 2.5 µg/L or GH < 1.0 µg/L in outcome definitions

Registry supportSODA registry reported combined endpoints (IGF-1 < ULN and GH ≤ 2.5 µg/L) to define control over 12–24 months

inv-57: urinary free cortisol response (Cushing's disease) — trial definition

Trial response definition (Cushing's)Urinary free cortisol reduced to ≤ upper limit of normal at specified timepoints (e.g., month 12 or month 60)

Long-term outcomePatients with mean urinary free cortisol at or below ULN or clinical benefit continued pasireotide in open-label extensions

Clinical implicationUFc response used as primary biochemical endpoint in pasireotide trials for Cushing's disease

inv-58: biochemical control — trial-specific definitions summary

Summary definitionBiochemical control definitions vary but generally combine GH thresholds (mean GH <2.5 µg/L, GH ≤2.5 µg/L, or GH <1.0 µg/L) with normalized age-adjusted IGF-1

Trial variabilityDifferent trials and registries use slightly different GH cutoffs and timepoints; reporting often includes both GH and IGF-1 outcomes

Use in authorizationThese trial-specific definitions inform continuation criteria and assessment of treatment response

inv-59: indication — FDA-labeled disease or use for each drug (label summary)

Signifor LAR (pasireotide) indicationsAcromegaly for patients with inadequate response to surgery or when surgery not an option; Cushing's disease when pituitary surgery is not an option or not curative

Somatuline Depot (lanreotide) indicationsLong-term treatment of acromegalic patients with inadequate response to or not candidates for surgery/radiotherapy; treatment of unresectable/metastatic GEP‑NETs; carcinoid syndrome

Lanreotide Injection indicationsLong-term treatment of acromegaly and treatment of unresectable/metastatic GEP‑NETs

inv-60: Somatostatin analogs label — general descriptor

Class descriptorSomatostatin analogs: synthetic octapeptide analogues of somatostatin that inhibit multiple endocrine and exocrine hormones

Typical effectsInhibit GH, glucagon, insulin, reduce GI hormone release and splanchnic blood flow; used for hormone-secreting tumors and symptomatic control

Formulation varietyAvailable as immediate-release (SC/IV) and long-acting depot formulations (IM or deep SC) for monthly administration