Orphan drug protection attached to a new claim for Amgen Inc.’s Neupogen (filgrastim) may preclude Sandoz Inc. from adding the same indication to labeling for its biosimilar Zarxio (filgrastim-sndz) in the near future.

On March 30, FDA approved Neupogen, a granulocyte colony-stimulating factor, for treatment of patients acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome, H-ARS).

The sBLA approval brings on-label an indication for which Neupogen has been stockpiled as a medical countermeasure.

Neupogen is the first FDA-approved medical countermeasure to increase survival in this patient population, the agency said.

FDA conducted a priority review of the supplemental BLA, and the indication carries orphan drug designation.

Seven Years Of Exclusivity

In November 2013, both filgrastim and Amgen’s Neulasta (pegfilgrastim) received orphan drug designation for treatment of subjects at risk of developing myelosuppression after a radiological or nuclear incident.

Under the agency’s orphan drug regulations, when a designated drug receives approval, “no approval will be given to a subsequent sponsor of the same drug for the same use or indication for seven years.”

This exclusivity would appear to have ramifications for Zarxio, which was approved March 6 as a biosimilar to Neupogen, with all five of the indications found on the Neupogen label at that time ([A#00150309013]).

FDA told “The Pink Sheet” that a biosimilar applicant that seeks approval for an additional condition of use after licensure must submit an efficacy supplement to its 351(k) application containing the necessary data and information.

The agency briefly addressed the impact of orphan drug exclusivity on biosimilar products in a 2012 Q&A guidance on implementation of the Biologics Price Competition and Innovation Act, which created the 351(k) biosimilar pathway.

The guidance states that FDA “will not approve a subsequent application for the ‘same drug’ for the same indication during the seven-year period of orphan exclusivity, except as otherwise provided in the FD&C Act and 21 CFR part 316.”

However, questions about the intersection of the 351(k) pathway and FDA’s orphan drug regulations have already arisen in the context of another biosimilar product.

Celltrion Inc. is seeking approval of CT-P13, a proposed biosimilar to Johnson & Johnson’s Remicade (infliximab), for all nine of the indications found on the reference product’s label. However, one of those indications is protected by orphan drug exclusivity until September 2018.

This situation led a former head of FDA’s Office of Orphan Products Development to point out that what is the “same” for purposes of biosimilarity might not be the “same” for purposes of orphan drug exclusivity ([A#14150209003]).

Although FDA’s review of CT-P13 was expected to shed some light on how orphan drug issues will play out in a biosimilar context, Celltrion’s application has hit a road bump. FDA postponed a March 17 advisory committee review due to information requests that were pending with the sponsor ([A#14150225006]).

The agency has not announced a new date for the meeting. The user fee date for the application, which is partnered with Hospira Inc., is June 8.

Sandoz said it would have to seek FDA approval to add the H-ARS indication to the Zarxio label and “at this time, we’re considering all of our options.”

Orphan exclusivity’s power to hold off subsequent approvals also is among the issues at play in Otsuka Pharmaceutical Co. Ltd.’s attempt to block FDA from approving generic versions of Abilify (aripiprazole) ([A#14150422008]).

‘Animal Rule’ Approval

Neupogen’s new indication was cleared under the “animal rule” because human studies are neither ethical nor feasible. Approval was based on animal models and data from adequate and well-controlled animal efficacy studies sponsored by the National Institute of Allergy and Infectious Diseases’ Radiation Nuclear Countermeasures Program, FDA said.

An FDA advisory committee considered the NIAID data during a May 2013 meeting, at which it voted 17-1 that filgrastim is reasonably likely to produce clinical benefits in humans exposed to radiation that is likely to induce myelosuppression during or following a radiological/nuclear incident Also see "Filgrastim As Radiation Countermeasure Gets Panel OK Despite Animal Rule Limits" - Pink Sheet, 13 May, 2013..

The sBLA approval brings on-label an indication for which Neupogen has been stockpiled as a medical countermeasure.

In 2013 the Biomedical Advanced Research and Development Authority purchased Neupogen under Project Bioshield for the U.S. Strategic National Stockpile to support the nation’s preparedness against a possible radiological or nuclear emergency. However, because the H-ARS indication was not approved, such use would have been considered investigational and required an emergency use authorization, FDA said.

Neupogen Claim’s Orphan Protection May Keep Zarxio At Bay

More from United States

More from North America