By Counterforce Health Team in Orladeyo (berotralstat) —

How to Get Orladeyo (berotralstat) Covered by Aetna CVS Health in Pennsylvania: Forms, Appeals, and Alternative Strategies

Answer Box: Getting Orladeyo Covered by Aetna CVS Health in Pennsylvania

Orladeyo (berotralstat) is excluded from most Aetna CVS Health formularies in 2024, requiring a formulary exception with documented failure of preferred alternatives like Takhzyro or Haegarda. Three-step process: 1) Submit prior authorization with HAE specialist documentation and C1-INH lab results, 2) If denied, file internal appeal within 180 days, 3) Use Pennsylvania's new external review program (53% success rate in 2024) within four months of final denial. Start with your prescriber today to gather required documentation.

Table of Contents

  1. When Formulary Alternatives Make Sense
  2. Aetna's Preferred HAE Prophylaxis Options
  3. Pros and Cons of Each Alternative
  4. Exception Strategy for Orladeyo
  5. Switching Between HAE Medications
  6. Building Your Case for Future Orladeyo Approval
  7. Appeals Playbook for Pennsylvania
  8. Cost Assistance and Patient Support
  9. FAQ

When Formulary Alternatives Make Sense

Aetna CVS Health excludes Orladeyo (berotralstat) from its 2024 Advanced Control, Standard Control, and most commercial formularies. Instead, they prefer Takhzyro (lanadelumab) and Haegarda (C1-INH subcutaneous) for hereditary angioedema (HAE) prophylaxis.

Before pursuing an exception, consider whether the preferred alternatives might work for you:

You might do well with alternatives if:

  • You're comfortable with injections (subcutaneous)
  • You want the highest efficacy rates (Takhzyro shows up to 87% attack reduction)
  • You haven't tried injectable prophylaxis before
  • Cost is a primary concern (formulary drugs typically have lower copays)

You likely need Orladeyo specifically if:

  • You have injection phobia or needle aversion
  • Previous injectable HAE medications caused intolerable side effects
  • You travel frequently and need oral convenience
  • You have injection site reactions or skin conditions
Tip: Even if you ultimately want Orladeyo, trying a preferred alternative first can strengthen your exception request by documenting "failure" or intolerance to formulary options.

Aetna's Preferred HAE Prophylaxis Options

Coverage at a Glance

Medication Formulary Status Route Frequency Prior Auth Required
Takhzyro Covered (Specialty Tier) Subcutaneous Every 2-4 weeks Yes
Haegarda Covered (Specialty Tier) Subcutaneous Twice weekly Yes
Orladeyo Excluded Oral Daily Exception only
Cinryze Limited coverage Intravenous Twice weekly Yes

Takhzyro (lanadelumab)

  • Mechanism: Monoclonal antibody targeting plasma kallikrein
  • Efficacy: Up to 87% reduction in HAE attacks versus placebo
  • Administration: Self-injection every 2-4 weeks
  • Common side effects: Injection site reactions, headache, dizziness

Haegarda (C1-INH subcutaneous)

  • Mechanism: Plasma-derived C1 esterase inhibitor replacement
  • Efficacy: ~95% median reduction in attacks versus placebo
  • Administration: Self-injection twice weekly
  • Common side effects: Injection site reactions, hypersensitivity
  • Note: Preferred in pregnancy and children ≥6 years

Pros and Cons of Each Alternative

Factor Takhzyro Haegarda Orladeyo
Convenience Moderate (q2-4 weeks) Lower (2x weekly) High (daily oral)
Efficacy Highest Highest Moderate (44-50% reduction)
Pregnancy safety Avoid Preferred Not preferred
Pediatric use ≥12 years ≥6 years Not approved <12
Aetna coverage Formulary Formulary Exception needed
Side effects Injection-related Injection-related GI symptoms

Access Considerations:

  • Testing requirements: All require confirmed HAE diagnosis with C1-INH functional/quantitative levels
  • Specialist involvement: Aetna typically requires HAE specialist (allergist/immunologist) evaluation
  • Monitoring: Regular follow-up for attack frequency and adverse effects

Exception Strategy for Orladeyo

When to Request an Exception

Request a formulary exception for Orladeyo if you have:

  • Medical contraindications to injectable therapies
  • Documented failure or intolerance to Takhzyro or Haegarda
  • Injection phobia with psychiatric documentation
  • Lifestyle factors making injections impractical (frequent travel, occupation)
  • Skin conditions preventing safe injection

Required Documentation

For your prescriber to include:

  1. HAE Diagnosis Confirmation
    • C1 esterase inhibitor functional and quantitative levels
    • C4 complement levels
    • Genetic testing results (if applicable)
    • Clinical history of recurrent angioedema
  2. Treatment History
    • Names, doses, and duration of previous HAE medications
    • Specific reasons for discontinuation (side effects, inefficacy)
    • Documentation of injection-related problems
  3. Medical Necessity Letter addressing:
    • Why Orladeyo is medically necessary
    • Why preferred alternatives are inappropriate
    • Expected clinical benefits
    • Monitoring plan

Strengthening Your Exception Request

Include supporting evidence:

  • FDA prescribing information for Orladeyo
  • Published clinical trial data (APeX-2 study)
  • HAE treatment guidelines supporting oral prophylaxis
  • Photos of injection site reactions (if applicable)
  • Mental health evaluation for needle phobia

Counterforce Health specializes in turning insurance denials into targeted, evidence-backed appeals by analyzing payer policies and crafting point-by-point rebuttals aligned to each plan's specific requirements.

Switching Between HAE Medications

From Injectable to Oral Therapy

No washout period required when switching from Takhzyro or Haegarda to Orladeyo. Clinical evidence supports direct transition without medication overlap.

Switching protocol:

  1. Coordinate with prescriber to time the switch appropriately
  2. Maintain attack diary starting 2 weeks before switch
  3. Monitor closely for first 3 months after transition
  4. Document any changes in attack frequency or severity

Real-world data: Patients switching from Takhzyro to Orladeyo in the APeX-S trial maintained low attack rates (0.1-0.5 attacks per month) with 98% attack-free days.

Insurance Coordination

Before switching:

  • Confirm Orladeyo prior authorization approval
  • Verify pharmacy benefits (specialty vs. medical)
  • Arrange prescription transfer if needed

After switching:

  • Submit updated prior authorization if required
  • Provide transition documentation to insurer
  • Keep detailed records for future appeals

Building Your Case for Future Orladeyo Approval

If you must try alternatives first, document everything to support a future Orladeyo request:

During Alternative Therapy Trial

Track meticulously:

  • Attack frequency and severity
  • Injection site reactions (photos, descriptions)
  • Impact on daily activities
  • Adherence challenges
  • Quality of life measures

Common documentation that helps:

  • "Patient reports injection anxiety affecting treatment adherence"
  • "Recurrent injection site reactions requiring topical steroids"
  • "Work travel schedule incompatible with injection requirements"
  • "Patient preference for oral therapy to improve long-term adherence"

Setting Up Success

Work with your HAE specialist to:

  • Establish clear trial endpoints (e.g., 3-6 months)
  • Define what constitutes "failure" or "intolerance"
  • Plan transition timeline to Orladeyo
  • Prepare medical necessity documentation

Appeals Playbook for Pennsylvania

Pennsylvania offers one of the strongest patient appeal rights in the nation with its new external review program launched in January 2024.

Step-by-Step Appeals Process

1. Internal Appeal (First Level)

  • Deadline: 180 days from denial
  • How to file: Aetna member portal or written request
  • Timeline: 30-45 days for standard; 72 hours for urgent
  • Required: Denial letter, supporting clinical documentation

2. Internal Appeal (Second Level)

  • Automatic: If first appeal denied
  • Timeline: Additional 30-45 days
  • Outcome: Final Adverse Benefit Determination letter

3. Pennsylvania External Review

  • Deadline: 4 months from final denial
  • How to file: pa.gov/reviewmyclaim or call 1-877-881-6388
  • Cost: Free
  • Timeline: 45 days for decision
  • Success rate: 53% of denials overturned in 2024

Required Documents for External Review

  • Final Adverse Benefit Determination letter
  • All internal appeal correspondence
  • Complete medical records
  • Prescriber statement of medical necessity
  • Any additional clinical evidence
Pennsylvania Success Story: In 2024, Pennsylvania's external review program overturned 259 out of 517 insurance denials, with many involving specialty drugs for rare diseases. The independent review organizations are binding on insurers.

Cost Assistance and Patient Support

Manufacturer Programs

BioCryst Patient Access Program

  • Copay assistance for eligible patients
  • Free drug program for uninsured/underinsured
  • Prior authorization support services

Foundation Support

National Organization for Rare Disorders (NORD)

  • Patient assistance programs
  • Advocacy resources
  • Disease-specific grants

State Resources

Pennsylvania Insurance Department

  • Consumer help line: 1-877-881-6388
  • Free appeal assistance
  • Insurance counseling services

FAQ

How long does Aetna CVS Health prior authorization take in Pennsylvania? Standard decisions typically take 30-45 days. Urgent requests are decided within 72 hours. Track your request through the Aetna member portal.

What if Orladeyo is non-formulary on my specific plan? Request a formulary exception with medical necessity documentation. You'll need to show why preferred alternatives (Takhzyro, Haegarda) are inappropriate.

Can I request an expedited appeal if I'm having breakthrough attacks? Yes. If your health is at immediate risk, both Aetna and Pennsylvania's external review offer expedited timelines (72 hours or less).

Does step therapy apply if I failed HAE medications outside Pennsylvania? Treatment history from any provider counts. Document previous failures thoroughly, including medications tried before moving to Pennsylvania.

How much does Orladeyo cost without insurance? The wholesale acquisition cost is approximately $44,484 per 28-day supply as of 2025. Patient assistance programs can significantly reduce out-of-pocket costs.

What counts as "medical necessity" for Orladeyo? Confirmed HAE diagnosis, documented failure or contraindication to preferred alternatives, and specialist recommendation that oral therapy is clinically appropriate.

Can I appeal if my employer plan denies Orladeyo? Self-funded employer plans are not covered by Pennsylvania's external review program. Check if your plan is subject to state regulation or uses federal external review.

How do I find an HAE specialist in Pennsylvania? The US Hereditary Angioedema Association maintains a provider directory. Major academic medical centers typically have allergist/immunologists experienced in HAE.

When navigating complex insurance appeals for specialty medications like Orladeyo, having expert support can make the difference between approval and denial. Counterforce Health helps patients, clinicians, and specialty pharmacies transform insurance denials into targeted appeals by analyzing payer policies and identifying specific approval criteria, then drafting evidence-backed rebuttals that address each plan's requirements.

Sources & Further Reading

Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult with your healthcare provider about treatment decisions. Insurance policies and coverage requirements may vary. For personalized assistance with Pennsylvania insurance issues, contact the Pennsylvania Insurance Department at 1-877-881-6388.

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