|The general configuration AIPPI attendee's|
saw the AmeriKat in during this year's Congress
"In the second Pharma session on Monday, Moderator Dominic Adair (Bristows, UK) and panellists Fritz Reiter, (Regulatory CMC Team Leader, Sandoz GmbH, AT), Prof. Mei-Hsin Wang (National Yunlin University of Science and Technology, TW) and Bryan Zielinski (Vice-President, Assistant General Counsel, Pfizer, US) debated the regulatory, substitution and interchangeability issues biosimilars are currently facing around the world, before giving an overview of relevant patent litigation strategies.
Dominic reminded the audience of a few interesting facts in the growing field of biosimilars. By way of background, small molecule drugs made of chemical substances have a structure which can be easily identified, and an identical compound can easily be synthesised. A chemical generic is an exact copy of the original molecule. In contrast, biological medicines are very complex. They involve living organisms and are thus more difficult to identify and characterise. Each biomolecule has a different "fingerprint" and it is impossible to obtain an exact copy of the original molecule. Thus, biosimilars have no generic "equivalent". This means that there is a much higher level of R&D investment in biosimilars as they take twice as long to develop as chemical generics. The R&D process is between 50-100 times more expensive. The consequence of this longer and higher cost developmental pathway is that companies who manufacture biosimilars may be more risk averse than small molecule generics in terms of their litigation appetite (in particular the consequence of injunctions). In addition, given the high cost and risk of bringing a biosimilar to market, the competitor landscape is less crowded. These factors directly impact litigation strategy.
From a regulatory perspective, biosimilars are expected to have no clinically meaningful difference for the patient in terms of safety and efficacy, and should be highly comparable to the reference biological medicine. They are interchangeable with the reference product. The global market of biosimilars has increased dramatically over the last few years and is currently worth one billion dollars. An ageing population and the increase in chronic diseases are driving a dramatic market expansion. Needless to say, biosimilar markets are having a significant impact on healthcare systems. Many innovator biopharma companies have thus developed and/or are developing biosimilars. Seven out of the top ten selling drugs are biosimilars. But how does one decide to chose a molecule to develop?
As Fritz pointed out, from a technical perspective, the past hurdles of manufacturing biosimilars have been successfully overcome. However, as a regulatory framework is not available in all markets, and due to the high value investments biosimilars require, the biosimilar market includes few players. Prof. Mei-Hsin Wang, dealing with the Asian perspective, explained how Asian countries, and Korea in particular, are massively investing in biosimilars.
All panellists agreed that the timing of the approval process of biosimilars products is the most significant factor in deciding whether or not a molecule should be developed and where, rather than the size of the market itself. According to Bryan Zielinski, the EU is the clear leader in setting up an appropriate regulatory framework for biosimilars. Although the US has already a different regime for biosimilars than for small molecule drugs, it is quite recent. The first regulation dates from 2010, and the implementing guidelines from 2012. The US and EU regulatory frameworks are not that dissimilar, just that the US trails the EU in time.
In this context, data and market exclusivity for originator products is a major issue. The panellists addressed the differences between the various systems. Prof. Mei-Hsin Wang explained the Japanese and Korean systems, where data exclusivity derives from Post Marketing Surveillance (PMS). During the PMS period, originator data cannot be referenced. The total RDP in Japan for a new drug is 8 years, 6 years in South Korea, contrasting with the 12 years in the US and 10 (+1) in the EU. Asian countries, as well as the US, are keen to push for a longer data exclusively period. Fritz Reiter specified that from a technical perspective, it does not really matter whether companies are locked out from filing a "dossier" for a biosimilar for a certain period of time, as the information included in the product label of the originator product is what biosimilars companies actually need.
The panel also discussed substitution and interchangeability. Bryan Zielinski explained the US perspective, where the FDA is reluctant to approve any biosimilar interchangeability designation. Even if the FDA sets up the overarching principles, it will still be up to the individual states to apply the rules on interchangeability. Reaching consistency throughout the different states seems unlikely. China and Taiwan are also very reluctant. In contrast, Japan and South Korea already agreed on interchangeability provisions.
The final debate focused on patent issues, in particular features of patent office post grant challenges, widely available and seen as a cheaper way to achieve freedom to operate in a patent landscape where there can be dense follow-on patent real estate ["Or thickets, if you are trying to appeal to the judge" declares Merpel]. Concerns were raised in relation to the estoppel issue under US law. A review of the main biosimilars patent litigation strategies closed the debate, with a particular focus on the pros and cons of the US declaratory judgment actions, as well as the patent resolution procedure which is currently under review before US courts. Dominic's final remarks related to the latest developments in the ongoing Fujifilm v Abbvie proceedings (see AmeriKat reports here), where the Arrow declarations sought are being used to clear the path with effective lifetime clearance."A recent Business Insider article reports that Pfizer estimates that with biologics with sales over $100 billion losing patent protection over the next few years, the biosimilar market is likely to increase to approximately $20 billion in 2020. Pfizer, who this spring obtained FDA approval for its Remicade biosimilar - Inflectra (infliximab-dyyb)- will join the likes of Novartis, Sandoz, Biogen and Amgen on the scene. This will mean that that the patent battles will start heating up over the next few years. Whether or not biosimilar manufacturers can effectively clear the path in a short, sharp burst with Arrow declarations in the UK or will have to clear the path the hard way, the patent litigation landscape on both sides of the Atlantic and further afield will be closely watched.