There is no evidence that ‘switching’ increases immunogenicity over time or reduces treatment efficacy
- Immunogenicity is a known risk for all biologics.
- A biosimilar will never be approved if there are any doubts that the immunogenicity is not comparable to the originator. The evaluation of comparable immunogenicity is a key element for regulators (US, EU, Japan, Australia and Canada) in their assessment of a biosimilar candidate prior to approval.
- The scientific principles for establishing biosimilarity are the same as those for demonstrating comparability after a change in the manufacturing process of an already licensed biological. Such changes or shifts, occur frequently and must be approved by regulators, that the product is equally safe and effective post-shift.
- Each individual batch of a biologic and biosimilar displays microheterogeneity. So by giving a patient continuing therapy of a “brand” biologic you always run a theoretical risk of inducing immunogenicity as the products are not the same and therefore the body will not recognise them as “self”.
- The overarching scientific understanding of inter-batch microheterogeneity is that the potential of immunogenicity in switching from an originator to a biosimilar is agreed to be no more or no less than using different batches of the same drug over time.
- In Australia, GCSF and EPO biosimilars have been successfully used since 2011 with over 1.5m patient days experience.
- GCSF is used per cycle for 5-10 days at a time with patients receiving multiple cycles and on-going chemotherapy when 1st line treatment fails. There are over 400 million patient days experience globally with GCSF biosimilars with no immunogenicity safety concerns. Data shows neutralizing antibodies aren’t common and, if detected, do not alter efficacy.
- Dialysis patients receive EPOs for many years and there is a huge amount of data showing this and also showing that immunogenicity does not increase over time. Data, as well as 400 million patient days experience globally with biosimilar EPO shows identical (or slightly less) issues with EPO immunogenicity in terms of PCRA and therefore treatment failure, as well as demonstrating the immunogenicity does not increase over time.
Substitution and switching will not impact safety and efficacy monitoring
- Substitution is recommended by the PBAC only after the TGA has determined that a medicine is comparable to the reference medicine. Both determinations are reliant on the government authorities evaluating data and providing a recommendation on whether the biosimilar is similar enough to the biologic so that approval of the product with reduced clinical and preclinical data can take place.
- If not, they would ask for it or reject the application. Substitution has not lead to confusion in the marketplace amongst healthcare professionals for generic medicines, and it is not expected that it would be any different for biologics.
- Current reporting has not identified a different rate or type of AE being reported for biosimilars, even though there is heightened awareness of the potential and hence potentially increased reporting of AEs.
Australia’s robust regulatory framework supports biosimilar market entry and patient access to life changing medicines
- Australia has a robust policy and regulatory framework, which ensures the quality, safety and efficacy of all medicines, including generic and biosimilar medicines, and allows generic or biosimilar medicines to be included on the pharmaceutical benefits list without the need to submit additional clinical data, beyond evidence of bioequivalence or biosimilarity, to be accepted as cost effective.
Based on the recommendations of the TGA, the PBAC and Minister can recommend listing of biosimilars, with the conditions of listing specified according to the demonstrated and accepted standard of equivalence