Celltrion's Biosimilar Strategy Includes Simultaneous EMA/FDA Reviews

Herceptin and Rituxan biosimilar applications expected to reach FDA early next year while EMA review is ongoing; timing could be another test for 351(k) pathway in US.

Celltrion Inc. plans to send its two upcoming biosimilar applications to FDA in the next few months while their European approval process is ongoing.

The company told the Pink Sheet that it intends to file for FDA approval of its biosimilars of Biogen Inc.'s Rituxan (rituximab) and Genentech Inc.'s Herceptin (trastuzumab) "early next year."

EMA review likely will be ongoing at the time Celltrion submits applications to the US FDA.

Celltrion submitted CT-P10, the proposed Rituxan biosimilar, for EMA approval in October 2015. CT-P6, the proposed Herceptin biosimilar, is expected to be submitted to EMA "this quarter," Celltrion told the Pink Sheet. CT-P10 and CT-P6 now are in late phase III development and have met their primary endpoints.

The news comes on the heels of Celltrion's announcement that Teva Pharmaceutical Industries Ltd. will commercialize both products in the US and Canada. Celltrion is responsible for completing the clinical development and regulatory activities for both products. (Also see "Teva Plugs Gap With Celltrion Deal For Rituxan And Herceptin Biosimilar Candidates" - Scrip, 6 Oct, 2016.)

Celltrion seems likely to commercialize the products itself in Europe, where it launched the company's only approved product, Remsima – a biosimilar of Janssen Biotech Inc.'s tumor necrosis factor blocker Remicade (infliximab) – in 2015.

Celltrion also has signed a deal with Pfizer Inc. to market Inflectra (infliximab-dyyb), its US version of Remsima. The product was approved in April and has passed its 180-day launch notification period, but Pfizer has not started marketing yet. (Also see "Inflectra Launch Prep Continues Post-Deadline, Pfizer Says" - Pink Sheet, 6 Oct, 2016.)

Will Dueling FDA/EMA Reviews Create Problems?

FDA and EMA could be conducting parallel reviews of one or both of Celltrion's upcoming applications, which could create a new situation for FDA's fledgling biosimilars program.

The company said the "FDA approval process is not correlated with [the] EMA timeline."

Some of the 351(k) products that the agency already has approved had been approved by EMA prior to seeking US clearance. That allowed FDA to use the sponsor's European experience and post-marketing data to help with its approval process.

In the case of Sandoz Inc.'s Zarxio (filgrastim-sndz), a biosimilar of Amgen Inc.'s Neupogen (filgrastim), advisory committee members in particular were comforted in recommending approval by Sandoz's extensive post-marketing experience with the product outside the US. (Also see "Neupogen Off-Label Use Complicates Data Extrapolation For Sandoz’s Biosimilar" - Pink Sheet, 19 Jan, 2015.)

Without an approval in the EU, Celltrion may face more scrutiny from FDA as well as the advisory committee, should the application reach that stage.

But FDA does have experience reviewing biosimilars without a prior post-marketing history. The agency reviewed Sandoz's Erelzi (etanercept-szzs), a biosimilar of Amgen's Enbrel (etanercept), while EMA's review was ongoing. FDA approved the product in late August. (Also see "FDA Biosimilar Policy Continues To Evolve With Approval Of Sandoz Erelzi" - Pink Sheet, 30 Aug, 2016.)

The advisory committee meetings already conducted for biosimilars in some cases have been difficult due to the complicated science and unfamiliar regulatory concepts.

Even though the agency does not focus on clinical data in biosimilar reviews, preferring to rely on analytical characterization, advisory committees have looked to clinical data for reassurance. (Also see "Amgen's Humira Biosimilar Gains Nod From Panel Perplexed By Regulatory Pathway" - Pink Sheet, 12 Jul, 2016.)

Start Of A 351(k) Wave

No applications for Rituxan and Herceptin biosimilars have reached FDA to date. And neither have been approved by EMA.

But Celltrion's filings also could be the beginning of a wave of 351(k) submissions in both drug classes.

Pfizer also is conducting studies of Herceptin and Rituxan biosimilars and Samsung Bioepis Co. Ltd. also is working on a Herceptin biosimilar. (Also see "Samsung Enters Oncology as Trastuzumab Accepted For EU Review" - Scrip, 4 Oct, 2016.)

FDA likely is expecting a number of 351(k) applications in the next few years, in part because it has many more biosimilar development programs in its system than anticipated. The agency changed the biosimilar user fee in part to deal with the workload. (Also see "Biosimilar User Fee Reboot: Resource Challenges Make FDA Eye New Structure" - Pink Sheet, 2 May, 2016.)