And Now for Something Completely Different… Eflapegrastim vs. Pegfilgrastim

On January 2, 2020, Spectrum Pharmaceuticals announced that the FDA had accepted its 351(a) application for a novel granulocyte colony-stimulating factor (G-CSF), eflapegrastim. And no, the name is not misspelled here; the name is a close cousin of pegfilgrastim.

As reported in 2018 by the Center for Biosimilars, this agent showed promise versus pegfilgrastim. As with the pegfilgrastim biosimilars, the road to approval for Spectrum has been bumpy. The manufacturer decided to withdraw its original application for approval in 2019 after FDA required more information on manufacturing of the eflapegrastim.

Not a follow-on agent or a biosimilar, eflapegrastim is intended to be introduced as a new innovative brand. As the early results hinted at somewhat greater potency than Neulasta®, the current application cites clinical data that supports noninferiority of eflapegrastim to Neulasta in terms of preventing febrile neutropenia. The study objective was to demonstrate noninferiority, not superiority. The phase 3 RECOVER investigation also found no significant differences in terms of safety between the agents.

One might ask, what’s the point of this product if it isn’t an improvement over pegfilgrastim? Well, it may be proven to be superior in some future study (though no further comparator investigations are currently listed on ClinicalTrials.gov).

It might possibly be an example of corporate inertia. Pfizer went through with its FDA approval of Ixifi™ (infliximab) even though it knew that it would not be marketing this biosimilar in the US. When Spectrum first submitted its application in December 2018, there were already two approved pegfilgrastim biosimilars, and one, Fulphila®, was being marketed. One wonders why Spectrum may have believed another branded G-CSF could still be an important player at that time.

Or the pharmaceutical company understood the small portion of marketshare that eflapegrastim could obtain, in the face of competition with three biosimilars and two forms of Neulasta in the long-acting G-CSF market. Even a small slice will be a difficult reach for Spectrum, especially since it will have to contend with actively lowering prices for the pegfilgrastim category.

The Food and Drug Administration set a PDUFA date of September 24, 2020 for eflapegrastim.

Evidence to Support Zarxio Use Presented at AMCP

Two posters presented at the Academy of Managed Care Pharmacy bolstered the case for moving away from the use of the originator filgrastim product Neupogen®.

In a study from Magellan Rx Management, Scottsdale, AZ, the researchers grouped both Zarxio® and Granixzarxio® together as alternatives to the originator filgrastim in the granulocyte-colony-stimulating factor (G-CSF) category as supportive oncological care. They studied the effect of a step edit, requiring the use of either Zarxio or Granix first, and its effect on utilization trends and cost savings among 2.7 million covered lives.

The step edit was implemented in October 2016 and the results for the fourth quarter of 2016 were compared with utilization and cost data from the first three quarters of that year. In terms of utilization, the marketshare of Neupogen dropped from 18% in early 2016 to only 2% by the third quarter of 2017. As expected, the drop in utilization occurred just after the step edit was introduced a year ago. The combined marketshare of Granix and Zarxio jumped from 9% to 21% over that time, but the dominant player in the G-CSF space, Neulasta® (pegfilgrastim), maintained utilization, rising from 73% to 77%. Over the one-year period since the step edit was introduced, the authors calculated a cost savings of $662,278; the cost savings in the quarter after the policy change was $106,980, or approximately 8% of the total spent for the G-CSF category.

The authors noted that the cost savings were calculated using wholesale acquisition cost (WAC) not average sales price (ASP), and manufacturer discounts or rebates were not considered in the estimates.

The second poster, sponsored by Sandoz, was a retrospective claims analysis of the incidence of febrile neutropenia in patients receiving chemotherapy who were treated with Zarxio or Neupogen. This study covered 13 months of claims (from Optum) from 162 patients taking Zarxio compared with 3,297 receiving Neupogen. The groups did not differ significantly in terms of demographics, insurance, or tumor type.

The researchers found that the incidence of neutropenia (in addition to fever and/or infection) was nonsignificantly greater in those receiving the biosimilar compared with the reference product (2.3% vs. 1.7%, respectively).