By Counterforce Health Team in Orladeyo (berotralstat) —

How to Get Orladeyo (Berotralstat) Covered by Cigna in California: Appeals Guide and Formulary Alternatives

Answer Box: Getting Orladeyo (Berotralstat) Covered by Cigna in California

Cigna requires prior authorization (PA) for Orladeyo (berotralstat) for hereditary angioedema (HAE) prophylaxis. Submit through your doctor with confirmed HAE diagnosis (low C4 and C1-INH levels), age ≥12 years, and documented failure/intolerance of formulary alternatives like Takhzyro or Haegarda. If denied, file an internal appeal within 180 days, then request California's Independent Medical Review (IMR) through DMHC for binding external review.

First step today: Have your HAE specialist gather your attack logs, prior therapy records, and lab results, then submit the Cigna PA form via their provider portal.

Table of Contents

  1. When Formulary Alternatives Make Sense
  2. Cigna's Formulary Alternatives for HAE Prophylaxis
  3. Pros and Cons of Each Option
  4. Exception Strategy: When to Request Orladeyo
  5. Step-by-Step: Fastest Path to Approval
  6. Appeals Playbook for California
  7. Common Denial Reasons & How to Fix Them
  8. Re-trying for Orladeyo Later
  9. FAQ

When Formulary Alternatives Make Sense

Before pursuing an exception for Orladeyo, it's worth understanding why Cigna prefers certain alternatives. Their formulary policies prioritize Takhzyro (lanadelumab) and Haegarda (C1 esterase inhibitor) based on established efficacy data and cost considerations.

Alternatives may be appropriate if:

  • You're comfortable with injections (subcutaneous every 2-4 weeks)
  • You haven't tried first-line prophylaxis options yet
  • Your attack frequency meets standard prophylaxis criteria
  • You want to avoid potential step therapy delays

However, Orladeyo remains the only oral prophylaxis option, making it essential for patients with injection phobias, needle access issues, or specific medical contraindications to injectable therapies.

Cigna's Formulary Alternatives for HAE Prophylaxis

Medication Administration Coverage Criteria Age Requirement
Takhzyro (lanadelumab) SC injection every 2 weeks Confirmed HAE due to C1-INH deficiency; low C4 and C1-INH levels ≥6 years
Haegarda (C1-INH) SC injection 2x/week Same HAE confirmation; favorable response to treatment ≥6 years
Cinryze (IV C1-INH) IV infusion 2x/week HAE prophylaxis; quantity limits apply ≥6 years

All require prior authorization through Cigna's Coverage Review Department with approvals typically lasting one year.

Note: HAE type III (normal C1-INH levels) is excluded from coverage for these medications.

Pros and Cons of Each Option

Takhzyro (lanadelumab)

  • ✅ Every-2-week dosing (less frequent than Haegarda)
  • ✅ Strong efficacy data (89% expert agreement as first-line)
  • ❌ Subcutaneous injection required
  • ❌ Higher cost than some alternatives

Haegarda (C1 esterase inhibitor)

  • ✅ Plasma-derived, well-established safety profile
  • ✅ 87% expert agreement as first-line prophylaxis
  • ❌ Twice-weekly injections
  • ❌ Requires cold storage

Orladeyo (berotralstat)

  • ✅ Only oral HAE prophylaxis option
  • ✅ Once-daily dosing
  • ❌ Drug interactions with P-glycoprotein inducers
  • ❌ Often requires step therapy documentation

Exception Strategy: When to Request Orladeyo

Request a formulary exception for Orladeyo when you can document:

Medical Necessity Criteria

  • Injection contraindications: Severe needle phobia, bleeding disorders, or injection site reactions
  • Prior therapy failures: Inadequate response or intolerance to Takhzyro or Haegarda
  • Drug interactions: Current medications that interact with injectable options
  • Patient preference: Strong clinical rationale for oral therapy

Supporting Evidence to Include

  • Attack logs showing frequency/severity over 3-6 months
  • Documentation of prior prophylaxis trials and outcomes
  • Specialist letter from allergist/immunologist
  • Lab confirmation (C4, C1-INH antigenic/functional levels)

When patients navigate the complex world of insurance coverage for rare disease medications, having expert support can make the difference between approval and denial. Counterforce Health specializes in turning insurance denials into successful appeals by analyzing denial letters, plan policies, and clinical notes to craft evidence-backed rebuttals that speak directly to each payer's specific requirements.

Step-by-Step: Fastest Path to Approval

1. Verify Coverage Requirements

Who: Patient or clinic staff
Action: Check your specific Cigna plan's formulary status for Orladeyo
Timeline: Same day
Source: Cigna member portal or pharmacy benefits

2. Gather Required Documentation

Who: HAE specialist and patient
Action: Compile attack logs, prior therapy records, lab results (C4, C1-INH)
Timeline: 1-2 weeks
Forms: Clinical notes, prescription history, diagnostic labs

3. Submit Prior Authorization

Who: Prescribing physician
Action: Complete Cigna PA form CNF-647
Timeline: 15 business days (standard) or 72 hours (expedited)
Submit via: Cigna provider portal or CoverMyMeds

4. Request Peer-to-Peer if Needed

Who: Physician
Action: Schedule clinical review with Cigna medical director
Timeline: Within 5 business days of request
Purpose: Discuss clinical rationale directly with reviewing physician

5. File Internal Appeal if Denied

Who: Patient or provider
Action: Submit appeal with additional evidence within 180 days
Timeline: 30 days for standard, 72 hours for expedited
Forms: Cigna medical appeal form

Appeals Playbook for California

Internal Appeal (First Level)

  • Deadline: 180 days from denial notice
  • Timeline: 30 days for determination (72 hours if expedited)
  • Submit to: Cigna Appeals Department
  • Required: Denial letter, medical records, physician statement

Independent Medical Review (External Appeal)

California's IMR process provides binding external review through the Department of Managed Health Care (DMHC).

  • Eligibility: After internal appeal or if Cigna doesn't respond within 30 days
  • Cost: Free to patients
  • Timeline: 45 days standard, 7 days expedited
  • Apply: DMHC website or call 888-466-2219
  • Binding: Cigna must follow IMR decision
California Advantage: The state's IMR system has historically favored patients in rare disease cases when proper medical evidence is provided.

Common Denial Reasons & How to Fix Them

Denial Reason Fix Strategy Documentation Needed
"Not medically necessary" Provide attack frequency logs and quality of life impact 3-6 months of attack records, specialist letter
"Step therapy not completed" Document prior therapy failures or contraindications Pharmacy records, prior authorization denials, adverse event reports
"Age restriction" Confirm patient ≥12 years Birth certificate or medical records
"Insufficient diagnosis" Submit complete HAE workup C4, C1-INH levels, genetic testing if available
"Concurrent prophylaxis" Clarify single-agent therapy plan Treatment plan showing discontinuation of other prophylaxis

Re-trying for Orladeyo Later

If you start with an alternative and want to switch to Orladeyo later, document:

During Alternative Therapy

  • Attack frequency and severity
  • Side effects or injection site reactions
  • Compliance challenges
  • Quality of life impacts
  • Any treatment gaps or failures

For Future Exception Request

  • Comparative effectiveness data
  • Reasons alternative therapy is inadequate
  • Patient preference for oral therapy
  • Updated clinical status

The key is maintaining detailed records that demonstrate why Orladeyo would be clinically superior for your specific situation. Counterforce Health helps patients and providers compile this evidence into compelling appeals that address each payer's specific coverage criteria.

FAQ

How long does Cigna prior authorization take for Orladeyo in California?
Standard review takes 15 business days; expedited review for urgent cases takes 72 hours. Source: Cigna PA policy

What if Orladeyo is completely non-formulary on my Cigna plan?
You can request a formulary exception with medical necessity documentation. California law requires insurers to have an exception process for non-formulary medications.

Can I request an expedited appeal in California?
Yes, if your condition is urgent. Both Cigna's internal appeal and California's IMR process offer expedited timelines (72 hours and 7 days respectively).

Does step therapy apply if I tried alternatives in another state?
Yes, documented prior therapy failures from any location should satisfy step therapy requirements if properly documented in medical records.

What's the success rate for HAE medication appeals in California?
While specific data isn't available, California's IMR system historically favors patients when proper medical evidence supports rare disease treatment requests.

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

Clinician Corner: Medical Necessity Letter Checklist

When preparing a medical necessity letter for Orladeyo, include:

  • Problem statement: HAE diagnosis with attack frequency/severity
  • Prior treatments: Specific medications tried, duration, outcomes
  • Clinical rationale: Why oral therapy is medically necessary
  • Guideline citations: Reference US HAEA guidelines supporting Orladeyo as first-line prophylaxis (81% expert agreement)
  • Dosing plan: 150 mg once daily with monitoring plan
  • Contraindications: Why alternatives are inappropriate
From our advocates: One patient's initial Cigna denial was overturned after their allergist documented severe injection anxiety that prevented consistent use of Takhzyro, leading to breakthrough attacks. The appeal included psychological evaluation and attack logs showing the correlation between missed injections and symptoms. This comprehensive approach addressed both medical necessity and patient-specific factors that made oral therapy essential.

Disclaimer: This information is for educational purposes only and does not constitute medical or legal advice. Always consult with your healthcare provider and insurance plan for specific coverage decisions. For assistance with appeals or coverage questions in California, contact the DMHC Help Center at 888-466-2219.

Sources & Further Reading

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