Cost-Utility Analysis of Ravulizumab Compared with Eculizumab in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria

O’Connell, Thomas; Buessing, Marric; Johnson, Scott J.; Tu, Lufei; Thomas, Simu K.; Tomazos, Ioannis

doi:10.1007/s40273-020-00929-z

Cited by 17 publications

(12 citation statements)

References 31 publications

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“…It does, however, remain a very costly drug, with access likely remaining limited for patients worldwide. 33,34 Whilst receiving licensed approval, there are areas for improvement with ravulizumab. Patients are still committed long term to lengthly 2-3 hour intravenous infusion every 8 weeks, requiring healthcare staff for administration and in some countries attendance at hospital.…”

Section: Ravulizumab Mechanisms Of Action and Clinical Trialsmentioning

confidence: 99%

A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going?

Griffin

Kelly

Pike

2020

Therapeutic Advances in Rare Disease

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Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-orphan disease, which until 15 years ago had limited treatment options. Eculizumab, a monoclonal antibody that inhibits C5 in the terminal complement cascade, has revolutionised treatment for this disease, near normalising life expectancy and improving quality of life for patients. The treatment landscape of PNH is now evolving, with ravulizumab a second longer acting intravenous C5 inhibitor now licenced by the FDA and EMA. With different therapeutic targets in the complement cascade and difference modalities of treatment, including subcutaneous, oral and intravenous therapies being developed, increasing independence for patients and reducing healthcare requirements. This review discusses the current and future therapies for PNH. Lay title Review of current and future treatments for patients with Paroxysmal Nocturnal Haemoglobinuria Lay summary What is Paroxysmal Nocturnal Haemoglobinuria? Paroxysmal nocturnal haemoglobinuria (PNH) is a very rare disease. It arises from PNH stem cells in the bone marrow. In a normal bone marrow these are inactive; however, if there has been a problem in the bone marrow, the PNH stem cells can expand and make PNH red blood cells, white blood cells and platelets. The problem with these cells is that they lack the cell surface markers that usually protect them. Red blood cells are broken down in the circulation rather than the spleen, which gives rise to PNH symptoms such as abdominal pain, difficulty swallowing, erectile dysfunction and red or black urine (known as haemoglobinuria). The white blood cells and platelets are ‘stickier’ increasing the risk of blood clots. Previously life expectancy was reduced as there were limited treatment options available. What was the aim of this review? To provide an overview of current and future treatment options for PNH Which treatments are available? • Eculizumab is an treatment given through a vein (intravenous) every week for 5 weeks then every 2 weeks after this, and has been available for 13 years, improving life expectancy to near normal. • Ravulizumab is a newer intravenous treatment similar to eculizumab but is given every 8 weeks instead of every 2 weeks. In clinical studies it was comparable with eculizumab. • Future Treatments - There is new research looking at different methods of treatment delivery, including injections under the skin (subcutaneous) that patients can give themselves, treatments taken by mouth (oral) or a combination of an intravenous and oral treatment for those patients who are not optimally controlled on eculizumab or ravulizumab. What does this mean? PNH is now treatable. For years, the only drug available was eculizumab, but now different targets and drug trials are available. Ravulizumab is currently the only second licenced product available, in USA and Europe, there are other medications active in clinical trials. Why is this important? The benefit for patients, from treatment every 2 weeks to every 8 weeks is likely to be improved further with the development of these new treatments, providing patients with improved disease control and independence. As we move into an era of more patient-friendly treatment options, the PNH community both physicians and patients look forward to new developments as discussed in this article.

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Section: Ravulizumab Mechanisms Of Action and Clinical Trialsmentioning

confidence: 99%

A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going?

Griffin

Kelly

Pike

2020

Therapeutic Advances in Rare Disease

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“…While such studies are limited in patients with aHUS, similar work has been carried out in different populations. Ravulizumab was found to be cost saving in a cost-utility analysis conducted by O'Connell et al, which compared the costs and benefits of both treatments in adults with PNH from a US payer perspective [50]. A semi-Markov model was used for analysis, and lifetime costs and benefit (assessed in quality-adjusted life-years [QALYs]) were discounted at 3.0% per year.…”

Section: Pediatric Patientsmentioning

confidence: 99%

“…Alexion Pharmaceuticals. A similar example of this scenario is the cost-utility analysis of ravulizumab and eculizumab conducted in patients with PNH[50]. Regardless of treatment manufacturer, the insights into the financial implications of treatment choice in aHUS provided here remain vital for guiding healthcare decision-making in this field.…”

mentioning

confidence: 98%

A US cost-minimization model comparing ravulizumab versus eculizumab for the treatment of atypical hemolytic uremic syndrome

Wang

Johnston²,

Popoff³

et al. 2020

Journal of Medical Economics

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Aims: Ravulizumab, engineered from eculizumab, provides sustained C5 inhibition in atypical hemolytic uremic syndrome (aHUS) while reducing dosing frequency (every 8 versus 2 weeks, respectively). Treatment choice often carries significant financial implications. We compared the economic consequences of ravulizumab and eculizumab for treating aHUS. Materials and methods: A cost-minimization model compared direct medical costs for ravulizumab and eculizumab in treating aHUS, assuming equivalent efficacy and safety, and took a US payer perspective, a lifetime horizon, and 3.0% cost discount rate. The base case modeled adult and pediatric treatment-naïve populations, with characteristics based on clinical trials, and treatment patterns (duration, discontinuation, re-initiation) derived from eculizumab studies with long-term follow-up. Treatment costs (2019 US$) were based on wholesale drug acquisition costs, Centers for Medicare & Medicaid fee schedules, and published disease management studies. Sensitivity analyses were conducted by adjusting relevant variables. Results: Ravulizumab provided lifetime per-patient cost reductions (discounted) of 32.4%

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“…However, the same complement tests (i.e., CH50 and sC5b-9) used for eculizumab may not consistently indicate adequate complement blockade (free C5 < 0.5 μg/mL) in monitoring therapy with ravulizumab ( 20 ). While this is an active area of research ( 21 , 22 ), recent studies suggest that ravulizumab offers a cost-savings and improved quality of life with less frequent dosing compared to the current cost of eculizumab ( 23 ) and adapted monitoring parameters (such as free C5 assays) are expected to be useful in individualizing the dosing of this drug as well.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Atypical HUS Presenting With Acute Rhabdomyolysis Highlights the Need for Individualized Eculizumab Dosing

et al. 2022

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BackgroundAtypical hemolytic uremic syndrome (aHUS) is an ultra-rare orphan disease caused by dysregulated complement activation resulting in thrombotic microangiopathy. Although complement-mediated endothelial injury predominantly affects the renal microvasculature, extra-renal manifestations are present in a significant proportion of patients. While eculizumab has significantly improved the morbidity and mortality of this rare disease, optimizing therapeutic regimens of this highly expensive drug remains an active area of research in the treatment of aHUS.Case PresentationThis report describes the case of a previously healthy 4 year-old male who presented with rhabdomyolysis preceding the development of aHUS with anuric kidney injury requiring dialysis. Clinical stabilization required increased and more frequent eculizumab doses compared with the standardized weight-based guidelines. In the maintenance phase of his disease, pharmacokinetic analysis indicated adequate eculizumab levels could be maintained with an individualized dosing regimen every 3 weeks, as opposed to standard 2 week dosing, confirmed in this patient over a 4 year follow up period. Cost analyses show that weight-based maintenance dosing costs $312,000 per year, while extending the dosing interval to every 3 weeks would cost $208,000, a savings of $104,000 per year, relative to the cost of $72,000 from more frequent eculizumab dosing during his initial hospitalization to suppress his acute disease.ConclusionThis case exemplifies the potential of severe, multisystem involvement of aHUS presenting with extra-renal manifestations, including rhabdomyolysis as in this case, and highlights the possibility for improved clinical outcomes and higher value care with individualized eculizumab dosing in patients over the course of their disease.

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Cost-Utility Analysis of Ravulizumab Compared with Eculizumab in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria

Cited by 17 publications

References 31 publications

A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going?

A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going?

A US cost-minimization model comparing ravulizumab versus eculizumab for the treatment of atypical hemolytic uremic syndrome

Case Report: Atypical HUS Presenting With Acute Rhabdomyolysis Highlights the Need for Individualized Eculizumab Dosing

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