By Counterforce Health Team in Orladeyo (berotralstat) —

If Orladeyo (Berotralstat) Isn't Approved by UnitedHealthcare in Michigan: Formulary Alternatives & Exception Paths

Quick Answer: Your Next Steps When Orladeyo Is Denied

If UnitedHealthcare denies Orladeyo (berotralstat) for your hereditary angioedema (HAE) in Michigan, you have three main paths forward: 1) Try a formulary alternative like Takhzyro, Haegarda, or Cinryze that may have easier approval criteria, 2) Request a formulary exception with additional clinical documentation, or 3) File an appeal through Michigan's external review process. Start by asking your HAE specialist which alternative makes the most clinical sense, then work together on the prior authorization paperwork. If all alternatives fail or aren't suitable, gather comprehensive attack logs and specialist letters for your exception request.

Table of Contents

  1. When Alternatives Make Clinical Sense
  2. UnitedHealthcare Formulary Alternatives for HAE
  3. Pros and Cons of Each Option
  4. Exception Strategy: Fighting for Orladeyo
  5. Switching Logistics and Pharmacy Coordination
  6. Re-trying for Orladeyo Later
  7. Appeals Process in Michigan
  8. Cost Assistance Options
  9. FAQ

When Alternatives Make Clinical Sense

Not every HAE patient needs Orladeyo specifically. UnitedHealthcare's formulary includes several effective prophylaxis options, and your specialist can help determine which might work best for your situation.

Consider alternatives when:

  • You're new to HAE prophylaxis and haven't tried other options
  • Orladeyo was denied due to step therapy requirements
  • You're comfortable with injections (subcutaneous or IV)
  • Cost or coverage stability is a primary concern

Stick with Orladeyo appeals when:

  • You've failed or can't tolerate other prophylaxis medications
  • You have documented contraindications to injection therapies
  • Your specialist believes oral therapy is medically necessary
  • You've had good results with Orladeyo in the past
From our advocates: One Michigan patient initially fought for Orladeyo for months, then tried Takhzyro as an alternative and found it worked just as well with faster approval. Sometimes the path of least resistance leads to equally good outcomes, though every case is different.

UnitedHealthcare Formulary Alternatives for HAE

Based on UnitedHealthcare's 2025 OptumRx formularies, all HAE prophylaxis medications require prior authorization and are subject to step therapy, but approval criteria vary slightly.

Primary Alternatives

Takhzyro (lanadelumab)

  • Route: Subcutaneous injection every 2-4 weeks
  • Age: 12 years and older
  • Mechanism: Plasma kallikrein inhibitor (similar to Orladeyo)

Haegarda (C1 esterase inhibitor, subcutaneous)

  • Route: Subcutaneous injection twice weekly
  • Age: 6 years and older
  • Mechanism: C1-INH replacement therapy

Cinryze (C1 esterase inhibitor, IV)

  • Route: Intravenous infusion every 3-4 days
  • Age: 6 years and older
  • Mechanism: C1-INH replacement therapy

Coverage Requirements Comparison

Medication Prior Auth Step Therapy Specialist Required Age Restriction
Orladeyo Yes Yes Yes ≥12 years
Takhzyro Yes Yes Yes ≥12 years
Haegarda Yes Yes Yes ≥6 years
Cinryze Yes Yes Yes ≥6 years

Source: UnitedHealthcare Commercial PDL

Pros and Cons of Each Option

Takhzyro (Lanadelumab)

Pros:

  • Similar mechanism to Orladeyo (kallikrein inhibitor)
  • Less frequent dosing (every 2-4 weeks)
  • Strong efficacy data in clinical trials

Cons:

  • Requires injections
  • May still face step therapy requirements
  • High cost (similar to Orladeyo)

Haegarda (Subcutaneous C1-INH)

Pros:

  • Can be self-administered at home
  • Available for younger patients (≥6 years)
  • Established safety profile

Cons:

  • Twice-weekly injections
  • Requires proper storage and handling
  • May cause injection site reactions

Cinryze (IV C1-INH)

Pros:

  • Longest track record among alternatives
  • Available for younger patients
  • Often considered first-line by some specialists

Cons:

  • Requires IV access every 3-4 days
  • More complex administration
  • May need home nursing or infusion center
Note: UnitedHealthcare prohibits concurrent use of multiple HAE prophylaxis medications simultaneously.

Exception Strategy: Fighting for Orladeyo

If alternatives aren't clinically appropriate, you can request a formulary exception. This requires comprehensive documentation showing why Orladeyo is medically necessary despite step therapy requirements.

Required Documentation

Clinical History:

  • Detailed attack logs showing frequency and severity
  • Documentation of previous prophylaxis attempts and outcomes
  • Contraindications or intolerances to formulary alternatives
  • Impact on quality of life and functional status

Laboratory Evidence:

  • C1-INH levels (antigenic and functional)
  • C4 complement levels
  • Genetic testing results if applicable

Specialist Support:

  • Letter from HAE specialist (allergist/immunologist)
  • Peer-to-peer review request
  • Clinical rationale for oral vs. injection therapy

Submission Process

  1. Gather comprehensive records from all previous HAE treatments
  2. Schedule specialist consultation to document medical necessity
  3. Submit formulary exception request through UnitedHealthcare provider portal
  4. Request expedited review if clinically urgent
  5. Prepare for peer-to-peer discussion with UHC medical director

Switching Logistics and Pharmacy Coordination

Transitioning between HAE medications requires careful coordination to avoid coverage gaps and ensure continuous protection.

Step-by-Step Switching Process

1. Provider Coordination (Week 1)

  • Schedule appointment with HAE specialist
  • Review previous therapy outcomes and side effects
  • Select most appropriate alternative based on clinical factors

2. Prior Authorization Submission (Week 1-2)

  • Submit PA request for new medication immediately
  • Include all required clinical documentation
  • Request expedited review if current therapy is ending soon

3. Pharmacy Verification (Week 2)

  • Confirm specialty pharmacy is in-network for new medication
  • Verify storage and administration requirements
  • Arrange delivery logistics and timing

4. Transition Planning (Week 2-3)

  • Plan overlap period if possible to ensure continuous coverage
  • Schedule training for new administration technique if needed
  • Set up monitoring appointments with specialist

5. Coverage Monitoring (Ongoing)

  • Track approval status through UHC member portal
  • Prepare appeal documentation if initial request is denied
  • Maintain attack logs during transition period
Tip: Request a 30-day supply of your current medication while the new PA is pending to avoid gaps in coverage.

Re-trying for Orladeyo Later

If you start an alternative medication, document everything carefully. This creates a stronger case for Orladeyo if the alternative doesn't work well.

What to Document During Alternative Therapy

Efficacy Tracking:

  • Attack frequency and severity compared to baseline
  • Time to achieve therapeutic effect
  • Breakthrough attacks despite therapy

Tolerability Issues:

  • Injection site reactions or administration difficulties
  • Impact on daily activities and quality of life
  • Any adverse events or side effects

Compliance Challenges:

  • Missed doses due to administration complexity
  • Travel or lifestyle limitations
  • Storage or handling problems

Building Your Case for Orladeyo

After 3-6 months on an alternative, you can resubmit for Orladeyo if:

  • Attack control is inadequate despite optimal dosing
  • Significant tolerability issues affect compliance
  • Administration method creates lifestyle limitations
  • Specialist recommends switching based on clinical response

Appeals Process in Michigan

If UnitedHealthcare denies your Orladeyo request or formulary exception, Michigan offers robust appeal protections through the Department of Insurance and Financial Services (DIFS).

Internal Appeals (First Step)

Timeline: 180 days from denial to file Process: Submit through UHC member portal or mail Decision: Standard 30 days, expedited 72 hours

External Review (Final Step)

Timeline: 127 days from final internal denial Process: File with Michigan DIFS using External Review Request form Decision: 60 days standard, 72 hours expedited Cost: No fee to patient

Contact Michigan DIFS:

  • Phone: 877-999-6442 (toll-free)
  • Website: michigan.gov/difs
  • Forms: Available online or by phone request
Important: Michigan's external review decisions are binding on UnitedHealthcare. If the independent medical experts rule in your favor, UHC must cover the medication.

Cost Assistance Options

While working through coverage issues, several programs can help reduce out-of-pocket costs:

Manufacturer Support

  • BioCryst Patient Access Program: Financial assistance for eligible patients
  • Copay assistance: May reduce monthly costs significantly
  • Free trial programs: Sometimes available for new patients

Foundation Grants

  • National Organization for Rare Disorders (NORD): Emergency financial assistance
  • HAE Association: Patient support and advocacy resources
  • State pharmaceutical assistance programs: Available for Michigan residents meeting income criteria

Counterforce Health Support

Counterforce Health helps patients navigate insurance denials by creating targeted, evidence-backed appeals. Their platform analyzes denial letters and plan policies to identify the specific reasons for denial, then drafts point-by-point rebuttals using the right clinical evidence and payer-specific requirements. This can be particularly valuable when dealing with complex specialty medications like Orladeyo, where appeals often require precise documentation of medical necessity and step therapy failures.

FAQ

How long does UnitedHealthcare prior authorization take in Michigan? Standard PA decisions take up to 15 business days. Expedited requests (when health could be seriously jeopardized) are decided within 72 hours.

What if Orladeyo is completely non-formulary on my plan? You can still request coverage through a formulary exception process. This requires stronger clinical documentation but is often successful for rare disease medications.

Can I request an expedited appeal if I'm having frequent attacks? Yes. If waiting for standard appeal timelines could seriously jeopardize your health, both UnitedHealthcare and Michigan DIFS offer expedited review processes.

Does step therapy apply if I tried alternatives outside Michigan? Yes, prior therapy history from other states counts toward step therapy requirements. Make sure to provide complete medical records from previous providers.

What happens if I can't afford the alternative medications either? Contact the manufacturer patient assistance programs for each medication. Most offer significant cost reductions or free medication for eligible patients.

How do I know if my specialist qualifies as a "HAE specialist" for PA purposes? UnitedHealthcare typically accepts allergists, immunologists, or hematologists. Your provider's specialty should be clearly indicated in the PA submission.

Can I appeal to Michigan state regulators if UHC keeps denying coverage? Yes. After exhausting UHC's internal appeals, you have 127 days to file an external review with Michigan DIFS, which provides an independent medical review.

What if I need Orladeyo for acute treatment instead of prophylaxis? Orladeyo is only FDA-approved for prophylaxis, not acute treatment. For acute attacks, your doctor should prescribe appropriate on-demand therapies like icatibant or C1-INH.

Sources & Further Reading

Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult with your healthcare provider and insurance plan for the most current coverage requirements and clinical recommendations. Coverage policies and state regulations may change. For personalized assistance with insurance appeals and prior authorizations, consider consulting with Counterforce Health or other patient advocacy services.

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