There are now licensed biosimilars to eculizumab available in Europe and also in the USA ( see previous article and further FDA announcement).
Biosimilars can be made available once the patent for the reference technology has elapsed.
There is not yet a biosimilar for Ravulizumab as it will be protected by a patent until the mid 2030s.
The brand names of the eculizumab biosimilars are Bekemv and Epysqli.
They are only available for the treatment of PNH and aHUS in countries which have approved the use and funding of eculizumab. If eculizumab is approved by the licensing bodies like the EMA or FDA then the procedures for biosimilars is much more simplified.
They do not need to go through the usual stages of getting approval by countries which approved eculizumab. Not even a clinical trial as is the case of aHUS .
The safety of the new drugs has been established in trials of PNH patients which is considered enough evidence for the drugs to be used for aHUS too.
No separate health technology appraisals and approvals are needed. So the drugs can swiftly become available as alternatives to Soliris.
A quick comparison of the drugs; delivery, ingredients, any patient exclusions , storage conditions and costs follows.
Equal efficacy is a given.
Bekdmv is manufactured by Amgen, Epysqli by Samsung Bioepsis, and we know already about Soliris and Alexion Astra Zenecca.
The monoclonal antibody ingredient eculizumab is the same for each.
All are infused at two weekly intervals. They are diluted with Sodium chloride 0.45% or 0.9% Glucose 5% for the infusion.
Undiluted Soliris has 500mmol of sodium in each 300 mg vial. Bekemv is more or less sodium free , i.e. with less than 1mmol per 300mg. So too is Epysqli, it has less than .57 mmol of sodium.
Bekemv contains sorbitol at 50ml and therefor is considered not suitable to be used in patients with HFI, i.e. heredity fructose intolerance.
Also use in children less than 2 years old use is not recommended because children that young may not well have been diagnosed with HFI yet.
Given intravenously it may be life threatening for HFI patients.
Soliris and Epysqli do not contain sorbitol.
The acidity (pH) of Soliris and Epysqli is 7.4, which would be around the acidity equivalent of blood, almost neutral. On the other hand Bekemv has a pH of 5.2 , less acidity but close to black coffee! Acidity is important for drug absorption, neutral is between 6 and 8 pH.
The recommended storage condition for each drug is similar i.e. in a fridge at 2 to 8 degrees C.
There are differences though in how long each drug can be kept at ambient temperatures.
Once out of a fridge all three undiluted vials should be used immediately. Soliris can be kept out a fridge for 3 days and then put back in a fridge but this can only be done once. So can Bekemv, but for 7 days and also only once. The same for Epysqli for 2 months before returning to a fridge.
Once vials of these drugs are diluted Bekemv can be stored for 96 hours in a fridge or 48 hours at room temperature (< 30 degrees). Diluted Epysqli can stored for 3 months in a fridge or 72 hours at room temperature. Diluted Soliris cannot be stored and must be used quickly.
The relative costs of a vial of the new drugs is not known. At present there is nothing published about the biosimilars prices. The list price of a vial of Soliris although known has remained the same for well more than a decade so it has gone down in real terms over time.
Also there are price agreement made between Alexion and health care organisations around the world which remain confidential but are likely to be lower than the list price. Biosimilar suppliers will have price agreements too.
Finally discontinuation of treatment practices of biosimilars would be the same as for Soliris.
A look now at what the NHS in England has said to patients about eculizumab biosimilars.
“Original version prepared the NHS Specialist Pharmacy Service: March 2024.
Eculizumab biosimilar: Patient Information Sheet
What is eculizumab?
Eculizumab is a medicine used to treat a number of different conditions including paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS). It belongs to a group of medicines called monoclonal antibodies.
How does eculizumab work?
In conditions where eculizumab is used the body’s inflammatory systems attacks its own cells. Eculizumab binds to a protein that causes the inflammation and prevents it attacking and destroying the body’s cells.
How is eculizumab made?
Eculizumab is a biological medicine. Biological medicines are medicines made or derived from living cells. Biological medicines were first used to treat people with serious illnesses in the UK over 20 years ago and they have improved the lives of millions of people worldwide.
What versions of eculizumab are available in the UK?
Until recently, only one pharmaceutical company made eculizumab. Now two other companies make a biosimilar eculizumab.
What is biosimilar eculizumab?
Biosimilar eculizumab is a highly similar copy of the original eculizumab medicine. The World Health Organisation (WHO) defines a biosimilar as a medicine that is similar in terms of quality, safety and effectiveness to the original licensed product.
Are biosimilars safe?
The body in the UK who regulate medicines is the Medicines and Healthcare products Regulatory Agency (MHRA). All medicines have to pass rigorous tests for quality, biological activity, safety and effectiveness. Biosimilar medicines pass the same tests as the original medicine.
What does treatment with biosimilar eculizumab mean for you?
Whether you are due to start treatment with eculizumab for the first time or have agreed with your clinician that your treatment will change from Soliris® to biosimilar eculizumab (Bekemv® or Epysqli®), you can expect the same results.
The National Institute for Health and Care Excellence (NICE) produces guidance for healthcare. If NICE recommends the original biological medicine in their guidance, the same recommendation applies to the biosimilar medicines.
All versions of eculizumab can cause similar side effects. If you experience any problems with your treatment, report it promptly to your treating clinician, nurse or pharmacist.
What are the benefits of biosimilars?
Many original biological medicines are expensive and the number of conditions they treat is increasing. Biosimilar medicines are highly similar to the original medicines and have the same quality, safety and effectiveness as well as being less expensive.
Therefore, the savings made by using biosimilars allow the NHS to treat more patients.
Further advice
If you have further questions about eculizumab or biosimilars, then please speak to a member of your specialist or pharmacy team.
Article No. 695
