Biosimilars – obtaining market access in Europe

Gaining freedom to operate was a central theme raised at the C5 Global Legal and Regulatory Summit on Biosimilars that we attended in Munich earlier this month.

Biosimilars are a category of medicines that seek to compete with originator biologic products. Biologics contain active substances derived from biological sources, such as human cells, and are often large, complex molecules with an inherent small degree of heterogeneity. Biosimilars are therefore not 'generic' products - where the active ingredient is chemically identical to the originator drug - but are highly similar alternatives to the originator reference product.

It costs more to make biologic products than small molecule drugs. This is reflected in the sale price of those medicines as manufacturers seek to make a return on their investments.

Patent rights play a central role in enabling biologic originators to protect their substantial investments and commercially exploit their time-limited monopoly in the market place. These patents and sister intellectual property rights, such as supplementary protection certificates (SPCs) in Europe and Patent Term Extensions (PTEs) in the US, can serve as a block to the launch of rival biosimilars. In Europe, SPCs can extend monopoly rights for up to a further five years following the expiry of the basic patent.

In many cases, biologics will be protected by both a product patent and a number of secondary patents. The more complex patent landscape can be attributed to the increased scope for patent claims that arise in the context of biologics than for traditional small molecule pharmaceutical products. While patent claims for small molecule drugs will commonly centre on a single compound, biologics claims often protect not just the molecule but also the mechanism of action, for example the ability of the drug to bind to or block a target, formulation, dosing regimen, medicinal uses and manufacturing processes.

In Europe, biologics are subject to a regulatory regime that provides originators with regulatory data protection for a period of eight years, such that the clinical trial data relied on by the originator for the purpose of obtaining a marketing authorisation cannot be relied on by a biosimilar manufacturer in obtaining their own marketing authorisation. There is also marketing protection, usually of a further two years, where the biosimilar manufacturer can submit an application for a marketing authorisation but cannot launch.

Orphan designated drugs, those for very rare diseases, may benefit from a 10 year period of market exclusivity, but such designations can be hard to come by and retain.

Paediatric extensions may prolong periods of exclusivity of SPCs by six months or orphan drugs by two years.

In practice the landscape of both patent and regulatory protection for biologics must be taken into account by manufacturers in developing their strategy to bring a biosimilar to the market.

For biosimilars, experience in Europe to date has shown that being one of the first to market following expiry of the originator product patent or SPC is important, otherwise rivals stand to gain first mover advantage and second or later entrants are forced to lower their prices or reconsider entering the market altogether.

In some cases it will be prudent to seek declaratory relief or challenge the validity of certain secondary patents held by biologic originator manufacturers that might otherwise hold up the launch of products. In other cases it might be more appropriate to seek a licence to use patented processes to guarantee market access for rival biosimilars.

A further factor that will shape where biosimilar manufacturers seek to launch their products is the local prescribing practice and reimbursement model.

In the US, biosimilars can struggle to penetrate a market where much of the power over what to prescribe rests with clinicians and where the market for reimbursement is more complicated with the involvement of doctors, health insurers and patients directly.

In Europe, reimbursement is more often handled through national health care systems, such as the UK's NHS, and in some countries biosimilar manufacturers have been boosted by initiatives to promote the use of their products in favour of more expensive originators. In Denmark, for instance, biosimilars approved by the European Medicines Agency based on reference originator biologics are automatically considered to be interchangeable and there is a mandate to switch to the lowest cost medicine.

While it is suggested that Europe is about 10 years ahead of the US in terms of the development of an established biosimilars market, it nevertheless remains necessary to navigate any barriers to launch. A product launch strategy that understands the opportunities and challenges of the patent and regulatory landscape will give biosimilar manufacturers the best chance of achieving commercial success and improving the lives of patients.