The FDA is a stone's throw away from approving its first official biosimilar a filgrastim follow-on developed by Sandoz International GmbH.
Holzkirchen, Germany-based Sandoz reported Thursday that the agency accepted its 351(k) biologics license application (BLA) for its biosimilar of Amgen Inc.'s Neupogen, a granulocyte-colony stimulating factor (G-CSF) used to treat neutropenia that came off patent last year. It's the first biosimilar BLA the FDA has accepted.
In keeping with the biosimilar user fee agreement, the agency now has 10 months to review the application before deciding whether to approve it. Barring regulatory issues or litigation, Sandoz may be able to launch its biosimilar as Zarxio in the U.S. in May 2015 as a competitor to Neupogen and Teva Pharmaceutical Industries Ltd.'s Granix (tbo-filgrastim), which was approved as a new, or 351(a), BLA in 2012 and launched late last year. (See BioWorld Today, May 7, 2013.)
It isn't surprising that, of all the reference biologics commonly targeted in the EU, Neupogen would be the first to face biosimilar competition in the U.S., as it is the first BLA-approved blockbuster to lose U.S. patent protection. Other biologics with biosimilar competition in the EU are still under patent in the U.S.
Outside the U.S., Sandoz 's filgrastim biosimilar has been making ripples for the past six years. Marketed as Zarzio in more than 40 countries, it was approved in the EU in 2009, in Australia in 2013 and in Japan earlier this year.
While Sandoz's G-CSF could be the first biosimilar approved in the U.S., it is one of 19 in the EU and the eighth in both Australia and Japan. A number of those approvals reference Neupogen. So far, eight filgrastim biosimilars have been approved in the EU, three in Australia and five in Japan. (Some of those are the same product, but they are being marketed by more than one company and under different names.)
Despite the crowded market, Zarzio is the No. 1 filgrastim biosimilar globally and is the leading daily G-CSF in Europe with 30 percent volume market share, making it the first biosimilar to overtake its reference product, according to Sandoz.
AMGEN'S FRANCHISE
Although still a blockbuster drug with nearly $1.4 billion in global sales in 2013, Neupogen is likely to lose that status once it faces biosimilar competition in the U.S., which accounted for nearly 84 percent of those sales. Outside the U.S., Neupogen recorded $229 million in 2013 sales. Its U.S. numbers were boosted by a $155 million order last year from the U.S. government, which added the leukocyte growth factor to the national stockpile as a radiation countermeasure. Amgen attributed the 11 percent increase in Neupogen's annual sales to that order. (See BioWorld Today, May 2, 2013, and Jan. 24, 2014.)
Ever since filgrastim biosimilars started coming on the market in the EU in 2008 and Neupogen faced competition from other G-CSF agents such as Chugai Pharmaceutical Co. Ltd.'s Granocyte (lenograstim), Amgen has been looking to its next-generation product, Neulasta (pegfilgrastim), to boost its filgrastim franchise. Neulasta saw $4.39 billion in global sales in 2013 up 7 percent from the $4.09 billion realized in 2012. Again, about 80 percent of those sales were in the U.S.
As with Neupogen, the sales of Neulasta are expected to drop when biosimilars of the long-acting G-CSF hit the EU and U.S. That could happen within a year or so, as Neulasta will lose patent protection in 2015 in both markets.
The product already has competition in emerging markets where follow-ons such as Intas Biopharmaceuticals Ltd.'s Neupeg and Amega Biotech SA's Peg-Filgrastim have been approved.
Several companies also are developing pegfilgrastim biosimilars for the highly regulated markets. Sandoz, for example, completed two phase III trials last year for LA-EP2006, a pegfilgrastim biosimilar, and is preparing to file for approval in the EU and U.S.
WHAT'S NEXT FOR SANDOZ
Sandoz also has a number of other biosimilars in the works, with four more molecules in phase III trials:
GP2015 (etanercept), referencing Amgen's Enbrel;
GP2017 (adalimumab), referencing Abbvie Inc.'s Humira;
GP2013 (rituximab), referencing Roche AG's Rituxan/Mabthera;
Epoetin alfa, referencing Janssen Pharmaceutica NV's Procrit.
The company's epoetin alfa, approved in the EU in 2007 as Binocrit, is the top-selling epoetin biosimilar on the market, with double-digit growth in 2013. Sandoz's other biosimilar, Omnitrope (somatropin), is No. 1 in its category, claiming more than 15 percent of the market in the EU and U.S., where it was approved in 2006 as a 505(b)(2) drug rather than as a biosimilar. When Omnitrope was approved in the EU in 2006, it became the world's first follow-on officially approved as a biosimilar.
An FDA approval of Zarxio would solidify Sandoz's position as the global biosimilar market leader, as it already has more than a 50 percent share of all biosimilars approved in the highly regulated markets of Australia, Canada, Europe and Japan.