FDA Biosimilar Policy Continues To Evolve With Approval Of Sandoz Erelzi

Third biosimilar approved in US brings another iteration of FDA thinking on labeling and naming; etanercept-szzs, which references Amgen's Enbrel, suggests agency might be backtracking on its suffix policy.

"Szzs" is probably a combination of letters only a linguist could love. But for sponsors hoping that FDA might change its policy on suffixes for biosimilars, it’s a syllable in the right direction. The Aug. 30 approval of Sandoz Inc.'s Erelzi (etanercept-szzs) means that the agency has now used three different approaches for adding suffixes for each of the three biosimilars it has approved – going from meaningful to random and now back toward somewhat meaningful.

Erelzi, which references Amgen Inc.'s TNF inhibitor Enbrel (etanercept), is Sandoz's second biosimilar approved in the US. The company's first, Zarxio, which references Amgen's Neupogen (filgrastim), was also the first biosimilar approved by FDA, and remains the only biosimilar to actually reach the US market. Zarxio's nonproprietary name, filgrastim-sndz, has a meaningful suffix, essentially an abbreviation of Sandoz.

When it approved Zarxio in 2015, FDA said the filgrastim-sndz name was a "placeholder" since it had not finished its policy development on biosimilar naming. The agency subsequently decided that biosimilars should have random, non-meaningful suffixes, and issued a proposed rule that both Neupogen and Zarxio get new nonproprietary names. (Also see "FDA Biosimilar Naming Policy Takes Middle-Of-The-Road Approach" - Pink Sheet, 27 Aug, 2015.)

There And Almost Back Again

FDA put its proposal into action in April when it approved Celltrion Inc.'s Inflectra, which references Johnson & Johnson's Janssen Biotech Inc.'s TNF blocker Remicade (infliximab). Inflectra's nonproprietary name, infliximab-dyyb, contains a random suffix, although the agency allowed Celltrion to provide both meaningful and non-meaningful suffixes for consideration. (Also see "Biosimilar Naming: FDA Asked Celltrion For Two Kinds Of Suffixes" - Pink Sheet, 15 Jul, 2016.)

Now with Erelzi, FDA seems to have taken a third approach. The szzs sequence isn't as identifiable as sndz, but it's also hard to say that a suffix which includes the first and last letters of the sponsor's name is non-meaningful.

FDA's thinking on suffixes could be further illuminated shortly. Amgen's pending biosimilar of AbbVie Inc.'s Humira (adalimumab) has a user fee date of Sept. 25, and it seems likely to be approved by then because it, like Erelzi, got a ringing endorsement from the Arthritis Advisory Committee last month. (Also see "Biosimilar Advisory Committee Reviews: Necessity Or Nuisance?" - Pink Sheet, 20 Jul, 2016.)

If FDA does formally change its policy on suffixes, it would represent a rare collaborative success by brand and generic firms on a biosimilar issue. The two sides can hardly agree on any aspect of how FDA should be implementing the review pathway, but one area where they do see eye to eye is in not liking non-meaningful suffixes – though of course the generic camp wouldn't like to see any suffixes at all. (Also see "Biosimilar Labeling: Should FDA Just Throw Up Its Hands And Finalize Guidance?" - Pink Sheet, 5 Aug, 2016.)

Regardless of how the suffix issue shakes out, it's likely to be an involved process for sponsors (Also see "FDA's Biosimilar Suffix 'Error': Molehill Withdrawn But Mountain Coming?" - Pink Sheet, 27 Jun, 2016.)

More Labeling Language On Biosimilarity

Beyond its nonproprietary name, Erelzi's prescribing information offers yet another iteration of FDA labeling ideas for biosimilars. Zarxio's label was basically identical to Neupogen (Also see "How To Label A Biosimilar? Copy The Reference Product, FDA Told Sandoz" - Pink Sheet, 15 Jun, 2015.). Inflectra was approved after subsequent FDA policy development, and its label mentions the brand, notes the product is a biosimilar, and describes biosimilarity (Also see "Biosimilar Template Revisited: Inflectra Approval Binds And Separates From Remicade" - Pink Sheet, 5 Apr, 2016.).

Erelzi's label adds another statement delineating the nature of the approval: "Biosimilarity of Erelzi has been demonstrated for the condition(s) of use (e.g. indication(s), dosing regimen(s)), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information."

That statement may be related to the limited range of dosing that Erelzi has relative to Enbrel. The biosimilar is approved for all Enbrel's indications, but because it's only available in prefilled syringes, Erelzi label says there is no weight-based dosing for children less than 63 kg, unlike Enbrel.

Enbrel also has a lyophilized powder. Those presentation differences could be a challenge for Sandoz seeking an interchangeability claim. (Also see "Biosimilars' Pediatric Pressures Could Push Them Toward Interchangeability" - Pink Sheet, 15 Jul, 2016.)

For now though, Sandoz first challenge will be getting Erelzi on the market after approval. The product is facing patent litigation from Amgen and Roche. (Also see "Biosimilar Litigation: Battles Continue Over Launch Notification, Access To FDA Info" - Pink Sheet, 26 Jul, 2016.).