Article No. 375
6 September 2020
Earlier this year, aHUS alliance Global Action wrote to a number of contacts it has around the world. Some information was sought about access to eculizumab in their countries. These contacts were from continents other than Europe ( including the EU) and also other than the USA in the Americas.
Nineteen contacts were identified , some were clinicians and some patient advocates .
Twelve replies were received from all but one continent and then sadly “events” overtook our programme of work.
With aHUS awareness day approaching, it is timely that we now report on what we were told by those respondents.
The twelve responses were from the following countries in alphabetical order Brazil, Canada, Chile, China, Egypt, India, Iran, Israel, Japan, Pakistan, South Africa and South Korea
The role of the respondents is shown in Table 1.
It may seem obvious but if Alexion is not prepared, for what ever reason, to market their products in a country for any of the diseases that would benefit them , then patients cannot access them.
In Table 2 the marketing status for eculizumab (and ravulizumab) is summarised.
Table 2: Is Eculizumab/Ravulizumab marketed in the country for aHUS/PNH?
|Continent||Country Responding||Eculizumab||Ravulizumab||Eculizumab Available for aHUS||Available for
|South Africa||Yes||No||No||Not known|
|ME & Asia||China||No||No||No||No|
In only 7 out the 12 countries responding was eculizumab marketed by Alexion: South Africa, Brazil, Canada, Chile, Israel, Japan and South Korea. In only one of those countries was Ravulizumab available i.e. Japan for PNH at that time; but it was expected that it would become available for aHUS soon.
Where known, in all countries where Alexion markets eculizumab it is available for PNH. As eculizumab for PNH precedes marketing for aHUS, it may be a predictor for the aHUS market to follow. This may be a predictor for ravulizumab too.
But if Alexion were prepared to market eculizumab would there be universal availability? If not what would restrict availability? . In 1 of those 7 countries, South Africa, there is currently no funding for eculizumab yet but the drug could be imported for limited use in some cases.
The first consideration would be how it would be funded and how affordable it would be?
. Table 3 shows how drugs like eculizumab would be paid for. The funding options would be private insurance , government funds or out of the patient’s pocket or combinations of each e.g all three may apply in Canada.
Table 3 How would eculizumab/ravulizumb be paid for ?
|Continent||Country Responding||Private Insurance||Government Funds||Out of pocket||Ecu Available||Income (k) per capita* (US $)|
|ME & Asia||China||*||No||10.4|
So in all cases where eculizumab is accessible , government funds are available to pay towards its costs. In three of those countries the patient would also be expected to contribute from out of their own pockets. In three countries private insurance would be needed to top up contributions. Not all private insurance will cover treatments like eculizumab.
All countries, but one, which funded eculizumab had a Gross National Income per capita greater that $11.5k ( world median level) . Only Brazil had a per capita income which was below I.e. $9:1k. Social funding of treatment is key to access and social funding generally depends on the Gross National Income per capita in the country. A consideration maybe, that underpins Alexion’s marketing strategy.
The six countries where eculizumab is not sold represent over 40% of the world population. China’s health policy precludes import of foreign orphan drugs, and the USA has a trade sanctions with Iran even if eculizumab was affordable there.
In those countries with access to eculizumab the barriers to universal access for the aHUS patients within each country was examined and summarised in Table 4.
Table 4 What are the restrictions to eculizumab/ravulizumab availablity for all aHUS patients?
|Continent||Country Responding||Restrictions on availability of ecu.||Regional policy variation||Legal approval||Scope -new onsets only||Time limits||Import controls
|ME & Asia||China||Yes||*||*|
|South Korea||Not known|
In only Japan and Israel is there unfettered access by all aHUS patients. In Canada and Chile some patients cannot access treatments because it may not be available in some parts of the country or only available to new onset patients or maybe time limited.
It is not known if there are any restrictions in South Korea. Advocates seeking access in countries with additional internal barriers face a bigger challenge in having to go through several different decision making groups , even legal groups and also fight discrimination against some patients.
Global Action also looked at other enablers to access which are found where freer access is available and may even encourage it.The existence of support practices which would back up a treatment if it were to become available, including expert centres, genetic testing facilities, vaccines and antibiotics against meningitis. Each was examined.
Table 5 Are meningococcal mitigating practices available?
|Continent||Country||Meningococcal Vaccination ACWY B||Prophylactic
|Africa||Egypt||Not known||Not known|
|South Africa||Not known||Yes|
|Americas||Brazil||Yes (ACWY only)||Yes|
|ME & Asia||China||Yes||Not known|
Countries had access to Meningococcal infection vaccines, which would be needed if eculizumab was to be used, although Brazil had no access the serotype B vaccination. Only five countries had access to prophylactic antibiotics too.
The existence of a national lead aHUS clinician, centre or professional organisation advocating for aHUS patients in their country is important and would be an enabler for aHUS patient treatment access
Table 6: Are there national expert and genetic testing centres for aHUS?
|Continent||Country||Recognised aHUS expert centre||Centre for genetic testing|
|ME & Asia||China||No||No|
Only one country, Chile, reported that there was an expert centre for aHUS. Four countries said there were natonal genetic testing facilities in their country including Iran which does not have access to eculizumab. Those with access, but no identifiable expert centre, were likely to have had some unknown clinicians participating in healthcare policy decisions which permitted use.
Table 7: Are the national treatment guidelines, eculizumab withdrawal and interval extension protocols
|Continent||Country||Are there national aHUS treatment guidelines?||Is there a national controlled ecu withdrawal process?||Are patients included in withdrawal decision?||Is there a national eculizumab dose extension process?||Is dose extension decided on case by case basis?|
|South Africa||Not known||No||–||No||–|
|Chile||Not known||Not known||Not known||Not known||Yes|
|ME & Asia||China||No||Not known||Not known||No||Yes|
|Israel||Yes||Not known||Yes||Not known||–|
In only four countries, Japan, South Korea and Iran are there national treatment guidelines for aHUS. No country reported a withdrawal from treatment national protocol but where it might happen three countries reported that patients would be included in the decision, Israel , Japan and South Korea.
Four countries Chile, China, Japan and South Korea reported that extension of dose intervals could be considered. It would seem that practices that could make eculizumab more cost effective are little known in countries in which it is unaffordable.
The Pharma supply and demand interface across different countries is complex. Asis shown in this study, pre-conditions are needed for both sides and then a “chicken and egg” situation needs to be resolved.
For the vast majority of aHUS patients around the world the current state is not in their favour and may never be. It cannot be down to a single solution for them and other ways need to be found and worked on to bring about the supply and demand equilibrium needed.
When that day comes there will be wellness and well-being for more.
aHUS Awareness Day is on 24 September 2020.