One of the first major incursions of biosimilars into the US market should happen by the end of the year when Teva launches Granix, a treatment for chemotherapy-induced neutropenia that will compete with Amgen’s Neupogen.
Although Granix achieved FDA approval on its own clinical merits under a BLA, it has the exact same recombinant active ingredient, filgrastim. It is not the first time biologicals have been subject to copycat competition in the US – after all, human insulin has been an intense rivalry for some time – but with many long-standing franchises reaching the end of their patent lives and regulators more receptive to biosimilars, Granix’s progress will be closely watched.
|G-CSF landcape - Major products in US and EU with sales forecasts||Annual sales ($m)|
|Product||Generic name||Proprietary level 1||Company||US patent expiry||2008||2012||2016||2018|
|TevaGrastim||filgrastim||Biosimilar||Teva Pharmaceutical Industries||-||-||-||100||150|
|Total WW sales (incl others)||5,238||5,819||4,899||4,119|
Short-acting under threat, what of long-acting?
The good news for Amgen’s granulocyte colony stimulating factor (G-CSF) franchise is that the Israeli generics giant has withdrawn its BLA for a Neulasta rival, Lonquex, a long-acting pegylated version of filgrastim.
This is a bit of cold comfort, however; the FDA still is reviewing the application for the long-acting albumin-fusion filgrastim called balugrastim. This could be launched at the same time as Granix if approval is granted, though this is not widely expecteed. A 2014 launch has been mooted by Teva, but the lack of sales forecasts attached to the product suggests that its arrival date is still hard to call.
Both Granix and balugrastim were subject to a 2011 patent settlement under which Teva cannot sell copycat versions of either product until November 10, 2013. Neupogen is a once-daily medication, while Neulasta can be used once per chemotherapy cycle.
In a technical sense, neither Teva product is a biosimilar in that the generics company applied for US licences under section 351(a) of the US Public Health Service Act, which governs novel biologicals; the true biosimilar pathway is section 351(k), which allows applicants to use data from the innovative product to support their applications. This is this technicality that has resulted in different international nonproprietary names, tbo-filgrastim and balugrastim.
Teva has a big opportunity in that Neupogen and Neulasta both are often on many pharmacy benefit plans' highest tier – number three or four. At a lower price, Granix and balugrastim stand a fairly good chance of being listed on the second, “preferred”, tier of those plans, offering patients an opportunity to have a lower cost-sharing burden at a time when they will have many medical expenses.
Still, as products that are incredibly similar, they serve as an example for what could happen in the US as biosimilars begin to enter the market as they have in Europe – Ratiograstim, a filgrastim biosimilar Teva obtained with the Ratiopharm acquisition, has been on the European market since 2008.
Significantly, all of the Teva filgrastim competitors in its various markets have resulted from an acquisition spree that has slowed in recent years. Their advantage is that they fit into the group’s emerging strategy of developing and marketing what it calls “new therapeutic entities” (Teva looks for plan B as investors desert, October 4, 2013).
|Teva's G-CSF portfolio|
|Product||Generic name||Current status||Originator|
|TevaGrastim||filgrastim||Marketed in EU||Sicor|
|Granix (Neutroval)||tbo-filgrastim||Approved in US Aug 2012||Sicor|
|Balugrastim||balugrastim||Filed in US||CoGenesys|
|Filgrastim BS||filgrastim||Marketed in Japan||Kowa Joint Venture|
|Ratiograstim||filgrastim||Marketed in EU||Ratiopharm|
|Lonquex||lipegfilgrastim||Approved in EU; filing withdrawn in US||Ratiopharm|
Learning from Europe
With the experience of European generic entry behind it, Amgen should be somewhat prepared for US competition for the short-acting drug. The peak year for Neupogen sales was 2008, the year of TevaGrastim’s entry, when it hit $1.34bn in sales; revenue has plateaued since, and is forecast to shrink to $701m in 2018.
On the other hand, the threat to Neulasta is a bigger deal, as the once-per-cycle product is second only to Enbrel in the California group’s sales rankings at $4.33bn this year. These worldwide revenues are expected to drop to less than $3bn in 2018, representing the biggest brake on growth over that time.
Biosimilar competition is emerging more slowly than expected as a result of disappointing regulatory guidance (FDA punts on interchangeability in biosimilar rule, February 10, 2012). In pushing near-generic versions of Neupogen and Neulasta through the regulatory process, Teva is showing one way competitors can succeed in getting to market; how the launch matures will be another lesson.