16 October 2020
aHUS patients envisage a treatment that is affordable for all one day. That will be a good day. For now all that can be hoped is that what ever complement inhibitor treatments there are become more cost effective and affordable as time moves on. That is the hope for Ravulizumab.
But what is cost effective? And cost effective in comparison with what treatment?
The only other clinically effective complement inhibitor is Eculizumab. How can Ravuliumab be compared with that?
That is a job for the Health Economists , using their cost -utility analysis tools. The most well known being the Incremental cost-effectiveness ratios ( ICERs). These are used to calculate a Cost per QALY.
As yet there is no cost per QALY result for Ravulizumab for aHUS in the public domain.
But there is one for the use of Ravulizumab to treat PNH.
It is a SAVING….just over -$1,000,000 per QALY
Compared with Eculizumab, a life time use of Ravulizumab is more affordable for treating PNH patients.
How did the Health Economists arrive at that figure? (It is fully explained in this article HERE)
Firstly there is a need to understand what a “QALY“ is.
A QALY is the benefit a patient gains from a treatment- it is a “product” ,so to speak, and as with any product it can be costed. It is a quality adjusted life year.
A QALY is arrived at by multiplying life years gained from a treatment and the change in quality of life to be expected in those life years for a patient on that treatment.
Quality of life (QoL) is measured on a scale from 1 to 10, from low to high quality. The difference in the quality of life gained between two treatments, say a score of 7 for a new treatment and 6 for its comparator adjusts any difference in life years.
Assuming 44 life years are forecast on a new technology whilst the old technology gave only 18 years , that would make a difference of 26 life years. Both the quality score and life years added are multiplied together i.e. 1 X 26 to give the number of QALYs. In this example it would be 26 QALYs gained from the new technology.
A “cost per QALY” is derived by dividing the total costs of treatment over a specific period of time, sometimes called a life time horizon, e.g example the average age of a patient needing treatment to the average life expectancy, or a stated number of years, 20 or maybe 25.
The average age at a PNH onset is around 46 if with treatment a patient can expect average life expectancy , say 72 , then the cost comparison could be based on 26 years of treatment. The average age when aHUS onsets is much younger, mid 20s, or a life time horizon of 46 years, so an aHUS economic evaluations might be limited to 25 years.
In the PNH calculation the number of QALYs gained were found to be 1.67. That is rather surprising since eculizumab and ravuliumab are just the same drug. Only one lasts longer between treatments than the other.
The quality of life improvement from fewer infusions would add something to the QALY, but not all of it. So what is it about?
Apparently the quality of life of PNH patients on Eculizumab has been reducing because of “breakthrough hemolyis” or “BTH”. The recommended label doses for Eculizumab has not been enough to block Complement and additional Eculizumab (at the aHUS adult dose levels) has had to be prescribed for some PNH patients. Up to 25% of PNH patients have been so affected.
Ravulizumab dose levels prevent BTH. So that would add to those patient’s quality of life and any patients in the future who will experience it (it can take about 12 years of use for it to happen).
But PNH researchers have also studied patients’ treatment preference. In a study of PNH patients, 93 % said they preferred Ravulizimab to Eculizumab for the kind of reasons which appeared in Global Action’s study of aHUS patients who have had experience of both treatments (that study report can be viewed in Article 384 ).
According to research, which collected feedback from patients, Ravulizumab produces 0.72 of a QALY for those PNH patients who do not experience BTH. That is lower than the overall QALY quoted above.
Most likely aHUS patients would say the same about their quality of life improvement from fewer infusions.
The life time horizon used in the costs of treatments is not stated, but the relative life time costs are reported at around $9.4m for Eculizumab and $7.8m for Ravulizumab. Hence a saving of more than $1.6m from Ravulizumab treatment.
Adult doses of Eculizumab for aHUS are higher than for PNH, (except for the PNH patients with BTH who get the same dose levels as aHUS patients). So the aHUS life time horizon costs for Eculizumab could be thousands of dollars more per year, say an additional $150 k for each year adding up to a life time cost of around £12.0 m at the same present day value as those reported for PNH ( i.e. reduced by 3% per year in the economic model, but so is the QALY- it is what economists do).
Yet Ravulizumab costs would remain roughly the same for both PNH and aHUS patients. So for aHUS there might be $4.2 m life time cost savings.
Putting the two figures, 0.72 and $4.2m, together and an incremental cost effectiveness ratio for Ravulizumab for aHUS results.
It would be a saving of around -$5.8 Million per QALY.
Maybe the lifetime savings are not as high relative to the PNH results nor the QALY be as high too. So other results are possible.
What ever the precise estimates will be, it is likely to remain that at list prices and label doses compared with Eculizumab, Ravulizumab is much more affordable.
And that is before the impact on the average cost of treatment from withdrawal of the treatment for some patients who no longer need it. Be it intermittently or permanently. Or off label dose adjustments.
Factor that in and the cost effectiveness of Ravulizumab could then even be challenging the much less clinically effective and burdensome PEX and dialysis treatment costs in some countries/ regions which turned Eculizumab down.
Future technologies will have to show at least the same clinical effectiveness and even more cost effectiveness than Ravulizumab and also make life freer and easier for aHUS patients.
.Previous articles about Ravulizumab