Biosimilars in the EU: delivering the goods?

The Forum Institute's 2009 seminar on biosimilars aimed to highlight the challenges facing their development and launch within the European market. Since the first biosimilar approval in early 2006, when Sandoz received backing for biosimilar human growth hormone (hGH) Omnitrope, the biosimilars market has evolved at considerable speed. Now, in 2009, payers, physicians and patients in the EU have the choice of multiple biosimilar medicines spanning several classes of biologic therapy, including hGH, erythropoietin (EPO) and filgrastim (G-CSF). However, while some would say the EU is indeed delivering the goods, significant challenges still exist.

The process is delivering the goods, but always evolving

During the seminar, leading experts from some of Europe's regulatory bodies discussed these challenges from a regulatory perspective. A representative from Germany's BfArM reaffirmed a belief held by many attendees that the EU system for reviewing and approving biosimilars worked and that the decisions emerging from the European Medicines Agency (EMEA) were based on sound scientific principles. That said, there are still concerns within the BfArM and the EMEA regarding low quality biosimilar products, immunogenicity, naming, and how each of the EU member states is handling the issue of interchangeability and automatic substitution. Moreover, despite the established nature of the biosimilars market in the EU, guidance is constantly evolving and guidelines will always need refining to include new scientific data and ongoing experience.

Automatic substitution (the ability for a pharmacist to automatically substitute a generic product when a brand is prescribed, without medical supervision) has been a critical driver of generics' uptake in many countries (e.g. France, Poland, Netherlands). In others, it has contributed to the lowering of generic prices (i.e. 'aut idem' rules in Germany) and has been a key influence on the speed of generic penetration (e.g. the US). Datamonitor believes that allowing automatic substitution within the biosimilars market is truly market shaping: with substitution in place, the decision to switch a patient's treatment is out of the physician's hands, placing the onus on the pharmacist, who would traditionally benefit financially from using the generic drug. It will also shape competition, as promotion and branding will not be required in a substitution market. Biosimilars would become attractive for classic generic players, shifting the base of competition firmly towards price. Indeed, without automatic substitution, biosimilars will be at the mercy of prescribers, who themselves are more likely to be influenced by promotional efforts and base their decisions on issues of efficacy and safety.

Biosimilar mAbs: the Holy Grail?

Perhaps the most hotly discussed topic at the moment is the concept of biosimilar monoclonal antibodies (mAbs). A presentation on the activities within the Committee for Medicinal Products for Human Use's (CHMP) biosimilars working party aimed to provide insight into the processes of the EMEA. Most attendees, however, were particularly interested in the comments on biosimilar mAbs. A key question raised was how far it is possible to go in providing guidelines for the development of biosimilar products. In principle, the concept of biosimilarity applies to any biological product, but the question remains as to whether regulators are able to provide guidance to the industry on the development of biosimilar mAbs. Ultimately, is the development of a biosimilar mAb possible at all?

The key driver of biosimilar mAb development is the commercial success of the wider mAb market. Datamonitor's analysis has shown that at the end of 2007, mAbs generated sales of $26 billion across the seven major markets and this is forecast to double by 2013. Moreover, highly sophisticated analytical and validation tools are now available which can aid in the characterization of biosimilar mAbs. However, concerns persist: mAbs are the most complex biologic therapies on the market, with glycosylation patterns critical to the overall activity of the final product. Poor reproduction of the correct glycosylation patterns has the potential to reduce biological activity of biosimilar mAbs, and could even render the biosimilar product extremely toxic.

It was argued that all of these issues represent significant regulatory challenges to the expansion of current biosimilar development guidelines, and multiple questions and concerns remain unanswered, specifically the extrapolation of indications to biosimilar mAbs, the design of clinical trials and what endpoints would be needed to prove safety and efficacy. The leading question, however, remains: considering their complexity, can there ever be a biosimilar mAb?

Biosimilar launch strategy: the case of Omnitrope

Many consider Sandoz to be one of the pioneers of the biosimilars segment in the EU. The approval of Omnitrope in 2006 heralded the birth of the biosimilars market, and since that time Sandoz has received approval for additional biosimilars EPO and G-CSF. While EPO has been well received in Europe, particularly in Germany, the uptake of biosimilar hGH has been tepid. A representative from Sandoz provided commentary on the launch of Omnitrope with a view to highlighting some of the key challenges of launching a biosimilar product.

Dedicated sales, marketing and medical support functions within a company are critical to the successful launch of a biosimilar. Datamonitor shares Sandoz's belief that until extensive positive experience with biosimilars has been obtained, member states are unlikely to allow automatic substitution for branded products, thereby defining biosimilar products as competitively priced me-too brands.

Datamonitor foresees a time when automatic substitution of simple proteins (e.g. insulin, hGH) is the norm across the EU, driven by payer pressure and the search for cost savings. Until that time, companies such as Sandoz must treat the biosimilars market as a branded market, committing significant clinical, medical and sales resource to any biosimilar projects in their pipelines. Moreover, in segments of the market that are device-driven (such as insulin and hGH), companies must provide competitive devices in order to drive uptake. Indeed, one criticism of Sandoz's early launch strategy for Omnitrope focused on the lack of a device, a factor that has potentially contributed to the poor uptake of the product. Following the company's launch of a competitive device, the OmniPen, uptake of Omnitrope is likely to improve.

'Generic biotech' - Obama's challenge in the US healthcare market

Aside from the potential for biosimilar mAbs, delegates were very keen to understand how the biosimilars market is likely to evolve in the US. Critically, concerns were raised as to how the newly elected US president, Barack Obama, will handle the 'generic biotech' issue that is generating extensive coverage. A key element of President Obama's election manifesto was "to provide quality, affordable and portable healthcare insurance to all US citizens." In order to achieve this, however, multiple issues must be resolved, including improved generic prescribing rates and the development and implementation of a biosimilars approval pathway. Datamonitor believes that progress on the implementation of the pathway will now gather momentum in the US, and will be approved by Congress in 2010. Key to this is the issue of data exclusivity: although branded pharmaceutical firms are arguing for 14 years of exclusivity, generic companies have provided compelling arguments that half of that time will allow innovator companies to recoup their investment.

Ultimately, for President Obama's universal access plan to succeed, all key stakeholders involved in the biosimilar debate-payers, physicians, patients and manufacturers-must be convinced of biosimilar safety and efficacy, first and foremost. Additionally, there must be adequate and sensible incentives in place for companies to develop biosimilars, physicians to prescribe them and patients to use them. For the affluent, privately insured segment of American society, the cost of therapy may not be much of an issue at the moment. However, for the uninsured, access to cheaper but equally effective biological therapies will represent a significant landmark.

Related research

Negotiating the Emerging Biosimilars Landscape: Key developments in the regulatory environment

Report: Biosimilars in the EU: delivering the goods?