Iptacopan and danicopan are two first-in-class agents that provide important health benefits, but there are uncertainties regarding long-term efficacy and safety —

BOSTON, February 1, 2024 – The Institute for Clinical and Economic Review (ICER) today posted its revised Evidence Report assessing the comparative clinical effectiveness and value of iptacopan (Novartis) and danicopan (Alexion Pharmaceuticals) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).  While important health benefits for patients were shown in clinical trials for both agents, there is uncertainty about long-term efficacy and safety. ICER’s model for iptacopan, which is already FDA-approved, using a shared-savings approach (described in more detail below), suggests that the drug would need to be priced 70% lower than the current list price to meet commonly accepted thresholds. For danicopan, which is not yet FDA-approved, ICER’s model suggests the price would need to be between $12,300 and $13,100 per year to achieve common thresholds for cost-effectiveness.

“PNH is a rare, acquired blood disorder that primarily manifests in fatigue, and if severe, requires lifelong dependence on blood transfusions,” said ICER’s Vice President of Research, Foluso Agboola, MBBS, MPH. “Complement C5 inhibitors, the current standard of care, have transformed this condition. However, C5 inhibitors are extremely costly, and patients, patient advocates, and clinical experts uniformly expressed concern about the access and affordability of these lifelong PNH treatments.  Iptacopan (as an alternative to C5 inhibitor therapy) and danicopan (as an add-on to a C5 inhibitor) are promising new oral options for PNH patients. We look forward to our public meeting at which all stakeholders can discuss the evidence for these new treatments, the tensions created by the cost of the current standard of care, and the extent to which the high costs of C5 inhibitors should drive considerations of fair pricing for new PNH treatments.”

This Evidence Report will be reviewed at a virtual public meeting of the California Technology Assessment Forum (CTAF) on February 16, 2024. The CTAF is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.

A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report and voting questions reflect changes made based on comments received from patient groups, clinicians, drug manufacturers, and other stakeholders. Detailed responses to public comments can be found here.

Key Clinical Findings

  • For treatment-experienced PNH patients on a stable C5 inhibitor: ICER rated the evidence for iptacopan versus continuing a C5 inhibitor as promising but inconclusive (“P/I”). For danicopan added to a C5 inhibitor, ICER rated the evidence as comparable or better than continuing a C5 inhibitor alone (C++). The current evidence is insufficient (“I”) to compare these agents to each other or to pegcetacoplan, another FDA-approved option for this population.
  • For treatment-naïve PNH patients: ICER rated iptacopan, which is also approved for this population, as insufficient (“I”) versus a C5 inhibitor, given the lack of comparative efficacy data.   

Key Cost-Effectiveness Findings

Iptacopan has been approved by the FDA (branded as Fabhalta®) and carries a list price of $550,377 per year. ICER’s analysis estimated that approximately 94% of the traditional cost-effectiveness value-based price of iptacopan comes from the cost offsets generated by eliminating the costs of the C5 inhibitor ravulizumab, which is priced at a level unaligned with its health benefits to patients. As detailed in our Value Assessment Framework, ICER applied an alternative cost-effectiveness methodology that shares the savings from cost offsets between the product innovator and the health system to calculate the health-benefit price benchmark (HBPB). Using these calculations, the HBPB for iptacopan is estimated to range between $156,000 and $157,000 annually.

Danicopan, an add-on therapy to a C5 inhibitor, has not yet been approved by the FDA, and the manufacturer has not yet announced the US price if approved. The HBPB range for danicopan is between $12,300 and $13,100 per year.

ICER’s HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, net of all rebates and discounts, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.