Is Vyepti (eptinezumab) therapy effective for a patient with chronic and disabling migraine who has failed multiple prior preventive treatments and only received two doses?

Recommendation on Vyepti Coverage Appeal

Based on Aetna's own coverage policy and FDA-approved prescribing information, this patient requires a third dose (completing 24 weeks of treatment) before treatment failure can be determined, and the current denial after only two doses contradicts both the insurer's stated criteria and the clinical evidence supporting extended treatment trials. 1

Aetna's Coverage Policy Supports Continuation

Aetna's Clinical Policy Bulletin 0970 explicitly states that continuation of Vyepti therapy is medically necessary when the patient has received "at least 3 months of treatment" - this patient has received 6 months (two doses) but requires assessment after the third dose at 24 weeks to properly evaluate response. 1 The policy requires demonstration of reduction in migraine days from baseline, but premature discontinuation at 6 months prevents accurate assessment of this endpoint, as clinical trial data measured primary efficacy at 12 weeks with sustained or improved response through 24 weeks. 2

FDA-Approved Treatment Duration and Response Assessment

The FDA label for Vyepti demonstrates that:

• Primary efficacy endpoints in both pivotal trials (episodic and chronic migraine) were measured over Months 1-3 (12 weeks), with studies continuing through 6 months to assess sustained response. 2
• In the chronic migraine trial (Study 2), patients received doses every 3 months for 6 months, with efficacy assessed across this full treatment period. 2
• The 300 mg dose this patient is receiving showed mean reductions of -8.2 monthly migraine days compared to -5.6 for placebo in chronic migraine patients, with responder rates continuing to improve through the second infusion. 2

Clinical Trial Evidence Demonstrates Response After Second Infusion

The DELIVER trial, which specifically enrolled patients with 2-4 prior preventive treatment failures (matching this patient's profile), showed that among initial non-responders during weeks 1-12,30.4% of patients receiving eptinezumab 300 mg became responders after their second infusion. 3 This means nearly one-third of patients who did not initially respond achieved meaningful benefit with continued treatment - denying the third dose eliminates this opportunity for response.

Key findings from DELIVER:

• Responder rates (≥50% reduction in monthly migraine days) increased from weeks 1-12 to weeks 13-24, rising from 71.0% to 74.5% with the 300 mg dose. 3
• The largest increase in responder rates occurred after the second infusion, demonstrating that treatment response develops or increases with subsequent dosing. 3
• Among patients who did not achieve ≥30% reduction during weeks 1-12,30.4% became responders after the second infusion with 300 mg dosing. 3

Real-World Evidence Supports 24-Week Treatment Duration

The EMBRACE II real-world study, which followed patients for 24 weeks (three doses), demonstrated that 69% of patients achieved ≥50% response and 39.2% achieved ≥75% response by week 24. 4 This study is particularly relevant because:

• It included patients with multiple prior treatment failures, including those who had failed other anti-CGRP monoclonal antibodies (32.4% of the cohort). 4
• Approximately one-third of patients escalated to 300 mg at week 12 (before the third dose) and achieved further significant reductions in migraine-related disability. 4
• Significant improvements were sustained through the full 24-week period, with continued benefit observed after the third dose. 4

Guideline-Based Treatment Duration for Preventive Therapy

Current migraine treatment guidelines recommend assessing efficacy of monoclonal antibody treatments targeting CGRP only after 3-6 months of treatment. 5 The Nature Reviews Neurology consensus statement specifically notes:

• For monoclonal antibody treatments that target CGRP or its receptor, efficacy should be assessed only after 3-6 months. 5
• Patients should be discouraged from abandoning treatment in early stages on grounds of apparent inefficacy, as efficacy is rarely observed immediately and may take several weeks or months to ascertain. 5
• Failure of one preventive treatment does not predict failure of treatment with other drug classes, except when failure is due to poor adherence. 5

Treatment-Refractory Population Indication

This patient's extensive treatment failure history (multiple oral contraceptives, baclofen, Flexeril, prior uterine ablation) makes her an ideal candidate for eptinezumab per FDA labeling and clinical trial populations. 2, 6 The DELIVER trial was specifically designed to evaluate eptinezumab in patients with 2-4 prior preventive treatment failures, demonstrating:

• Statistically significant reductions in mean monthly migraine days (-5.3 days with 300 mg compared to -2.1 days with placebo, p<0.0001). 6
• Efficacy across clinically relevant subgroups, including patients with chronic migraine, medication overuse, and multiple prior treatment failures. 6
• The VA/DoD Clinical Practice Guideline explicitly recognizes that eptinezumab "has value among patients who have been treating refractory migraine." 1

Dose Escalation to 300 mg Provides Additional Benefit

The FDA label explicitly notes that some patients may benefit from the 300 mg dose every 3 months, and this patient is appropriately receiving this higher dose given her refractory disease. 2 Real-world evidence demonstrates:

• Patients escalating to 300 mg at week 12 achieved further significant reductions in migraine-related disability beyond what was observed at lower doses. 4
• The 300 mg dose showed numerically greater efficacy than 100 mg across all responder rate thresholds in treatment-refractory patients. 6

Rapid Onset and Sustained Effect

Eptinezumab demonstrates onset of effect from day 1 after infusion, with benefits sustained and often increasing with subsequent doses lasting up to at least 2 years. 7 This rapid onset combined with sustained effect supports:

• Continued treatment through at least the third dose to allow full assessment of therapeutic benefit. 7
• The potential for cumulative benefit with repeated dosing, as demonstrated by increasing responder rates after the second infusion. 3

Safety Profile Supports Continued Treatment

Treatment-emergent adverse events with eptinezumab occur at low frequency (≥2% of patients), with the most common being upper respiratory tract infection and fatigue. 7, 8 The favorable safety profile supports:

• Continuation of treatment through the third dose poses minimal safety risk. 8
• Adverse events are typically mild and do not necessitate treatment discontinuation. 8

Clinical Justification Summary

This patient meets all criteria for continued Vyepti coverage:

1. Formal diagnosis of chronic migraine with daily headaches and menstrual exacerbation. 2
2. Extensive history of failed preventive treatments, making her an ideal candidate per FDA labeling and DELIVER trial population. 2, 6
3. Received only two doses (6 months) when evidence demonstrates that responder rates increase after the second infusion and that 24 weeks (three doses) is the appropriate duration to assess efficacy. 3, 4
4. Already receiving the appropriate 300 mg dose for treatment-refractory disease. 2, 4
5. Aetna's own policy requires at least 3 months of treatment before determining failure, and clinical evidence supports assessment after three doses (24 weeks). 1

Denying coverage after only two doses contradicts Aetna's stated coverage criteria, FDA-approved treatment duration, clinical trial evidence, real-world data, and current treatment guidelines - all of which support continuation through at least the third dose before determining treatment failure. 1, 2, 3, 4, 5