Access to eculizumab

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.

Role   No. responding
Clinician /Researcher 3
Patient Advocate  3
Patient Carer 6

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
Africa Egypt No No No Not known
South Africa Yes No No Not known
Americas Brazil Yes No Yes Yes
Canada Yes No  Yes Yes
Chile Yes* No Yes Yes
ME & Asia China No No No No
India No No No No
Iran No No No No
Israel Yes  No Yes Yes
Japan Yes Yes* Yes Yes
Pakistan No No No No
South Korea Yes No Yes Yes
Oceania None 

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 $)
Africa Egypt *     No 2.7
South Africa *   * No 6.0
Americas Brazil * *   Yes 9.1
Canada * * * Yes 46.4
Chile * *   Yes 15.0
ME & Asia China   *   No 10.4
India       No 2.1
Iran     * No 5.4
Israel   *   Yes 43.3
Japan   * * Yes 41.7
Pakistan       No 1.5
South Korea   * * Yes 31.4
Oceania None

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
Africa Egypt Not applicable 
South Africa Yes *
Americas Brazil Yes *
Canada Yes * * *
Chile Yes * * *
ME & Asia China Yes * *
India Not applicable
Iran Yes *
Israel None
Japan None
Pakistan Not applicable
South Korea Not known
Oceania None

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
Canada Yes Not known
Chile Yes Yes
ME & Asia China Yes Not known
Iran No
Israel Not known Yes
Japan Yes Yes
South Korea Yes No
Oceania None

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
Africa Egypt No No
South Africa No No
Americas Brazil No No
Canada No No
Chile Yes Yes
ME & Asia China No No
India No Yes
Iran No Yes
Israel No No
Japan No No
Pakistan No No
South Korea No Yes
Oceania None

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?  
Africa Egypt No No Not known
South Africa Not known No No
Americas Brazil No No No
Canada No No No No  No*
Chile Not known Not known Not known Not known Yes
ME & Asia China No Not known Not known No Yes 
India No
Iran Yes
Israel Yes Not known Yes Not known
Japan Yes No Yes No Yes
Pakistan Not known
South Korea Yes No Yes* No Yes
Oceania None

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.

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