Considered one of the biologics most likely to meet a biosimilar competitor anytime soon, Enbrel’s newly granted patent should help Amgen in any infringement squabbles that are surely set to ensue.
Granted unexpectedly by the US Patent and Trademark Office yesterday, the new patent describes the protein and has a term of 17 years - a substantial stretch thanks to long-lapsed rules that apply to patents filed before mid-1995. Encouraging news no doubt, but the development is unlikely to deter the numerous companies developing copycat versions of the blockbuster arthritis therapy (see table below).
Amgen announced the patent’s allowance last night; referred to as ‘182, this was filed before the US brought its patent laws in line with international standards in 1995 and was therefore entitled to a 17 year term from issuance. Patents filed after 1995 get 20 years from the date of filing.
Like any small molecule manufacturer, biotech giant Amgen is of course keen to protect its brand for as long as possible and this is exactly the strategy here. Describing very specifically the sequence of amino acids in the protein and method of production, the company is attempting to make life harder for biosimilar challengers.
While this patent should achieve this to a certain extent, it is unlikely to throw up an impenetrable barrier, analysts believe.
“This is obviously a positive for Amgen but not a huge positive. There are ways to get around this and precedent has shown this can be done,” says Ram Selvaraju, biotech analyst at Morgan Joseph TriArtisan. He does not cover Amgen.
“The reason why Shire has the ability to sell Vpriv in the US is that even though it is the same molecule [as Genzyme’s Cerezyme] they changed one amino acid residue and used a different method of production. So the original patents were not enforceable because they don’t infringe,” he says.
However while the new patent will not deter challengers from emerging, until it is tested its usefulness will remain unclear.
“Given its specificity, and the clear utility of the fusion protein invention, it is hard to imagine it being completely invalidated or overruled in litigation,” Geoffrey Porges at Bernstein wrote today. He has an outperform rating on the stock.
Mr Selvaraju believes companies are likely to be employing different production techniques to generate a biosimilar Enbrel protein anyway, getting around this aspect of the new patent. For example Protalix Biotherapeutics is using its plant-based technology platform. Meanwhile by making a very small change in the amino acid sequence, the sequence claims could also be circumvented.
“The problem then is by changing the sequence, would you change the immunogenicity and would the FDA ask for head-to-head trials? I think the answer is probably no,” he says, given that Enbrel is a very well known and well studied molecule.
One of the most prominent developers of an Enbrel biosimilar is Merck & Co. Only this year the pharma giant paid an undisclosed sum to Korean company Hanwha for global rights to HD203, now called MK-8953 (Jostling for position continues in biosimilars market, June 14, 2011).
The compound is currently undergoing phase III therapeutic equivalence testing versus Enbrel in Korea and is in phase I in the US. Long awaited guidance from the FDA on the path to market for these products will influence how quickly pivotal testing can start (US biosimilar rules due by year end, November 23, 2011).
Merck is considered one of the leading candidates to blaze a trail for biosimilars in the US, and analysts reckon generic Enbrel could be the flagship product for its BioVentures business. MK-8953 is thought to use the same amino acid sequence as Enbrel while details of the production technology have yet to emerge.
The original patents protecting Enbrel lapse towards the end of 2012, although biosimilars are not anticipated until 2015 at the very earliest given the challenges in getting them to market quickly.
Global sales of Enbrel are seen peaking at $8.21bn in 2014, and falling back to $7.35bn by 2016, consensus data from EvaluatePharmashow. This predicted decline is likely due to a numbers of factors, biosimilars being one, but also competition from other RA therapies, in particular Pfizer’s tofacitinib.
As the first oral therapy its appearance potentially next year is arguably as big an event on the horizon for Enbrel as more direct competitors.
|Anti-TNF biosimilars in development|
|Phase III||CT-P13||infliximab (Remicade)||Celltrion|
|MK-8953 (HD203)||etanercept (Enbrel)||Merck & Co / Hanwha Group|
|TuNEX||etanercept (Enbrel)||Mycenax Biotech|
|Phase I||GS071||infliximab (Remicade)||Nichi-Iko Pharmaceutical / Schnell Biopharmaceuticals|
|TNFcept||etanercept (Enbrel)||LG Life Sciences|
|Etanercept||etanercept (Enbrel)||Bio Sidus|
|Pre-clinical||TNF MAb||infliximab (Remicade)||LG Life Sciences|
|CT-P13||infliximab (Remicade)||Nippon Kayaku|
|Etanercept||etanercept (Enbrel)||Daewoong Pharmaceutical|
|PRX-106||etanercept (Enbrel)||Protalix Biotherapeutics|