The United Kingdom now has its first biosimilar insulin, following the 2015 launch of Abasaglar, a version of U100 insulin glargine made by Eli Lilly. The same insulin, but branded Basaglar, has also been approved by the Food and Drugs Administration (FDA) in the United States, this following on from their first biosimilar approval – Zarxio (filgrastim) – in March 2015. The term ‘biosimilar’ is preferred to ‘generic’ because the complexity of insulin production techniques mean that small differences from the already-approved reference product cannot be excluded. The biosimilar must show it has no clinically meaningful differences in terms of safety and effectiveness from the reference agent and only minor differences in clinically inactive components are allowable in biosimilar products.
These events are in contrast to the decision made in November 2015 by the Committee for Medicinal Products for Human Use (CHMP) to recommend refusal for marketing authorisation of Solumarv. Solumarv is another biosimilar insulin, this time a short-acting one, made by Marvel Lifesciences Limited and the reference product is Humulin S.
The different responses probably indicate that the regulatory authorities take into account more issues other than just the clinical studies. For example, the CHMP commented that Marvel ‘did not define the manufacturing process for Solumarv in sufficient detail. As such, it was not possible to show that Solumarv used in clinical studies was representative of batches intended for the market and that its quality was comparable to Humulin S’s’. There are also concerns about companies’ ability to maintain supplies of their biosimilar product; since the biosimilars are inevitably cheaper than reference insulins, widespread switching is possible and any supply issues could have major consequences. In this respect Eli Lilly’s heritage in diabetes is important – they were the first company to commercially produce insulin in 1921 and have done so ever since.
Perhaps these considerations should also apply to generic molecules, where pharmacy-led switching is now commonplace? A case in point is that of pioglitazone (Actos, produced by Takeda) which went off-patent in 2012. Immediately, generic versions became available at a large price discount and NICE in the first draft of its type 2 diabetes guideline update moved pioglitazone into the preferred second-line option following metformin. Then in December 2015, United Kingdom Medicines Information (UKMi) issued a memo on ‘shortage of supply’ for all strengths of pioglitazone. Limitation of prescribing to 28 days was suggested as an option to reduce the risk of stocks running out (odd, given that almost all patients renew their prescribed medications on a monthly basis) with medication review recommended for those patients who cannot obtain supplies. What was not mentioned was that the shortage was down to supply-chain issues in the generic companies, with Takeda being able to make up the short-fall (which would probably not have happened if patients had remained on or been initiated with the branded reference product). I suspect the costs of this episode will never be calculated and there will be little account taken of the concerns and inconvenience suffered by patients.
More insulin biosimilars will emerge over the coming years and more anti-diabetic medicines will lose patent protection. The potential for future mishap seems very real…
Professor Steve Bain