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10/25/2016

Filgrastim Becomes Biosimilar Test Case for Hospitals

Kate Traynor

Kate TraynorNews Writer
News Center

Steve Pickette, assistant director of clinical services at the University of Washington Harborview Medical Center, expects the Seattle facility to reap substantial savings after adding Zarxio, Sandoz Inc.'s biosimilar version of filgrastim, to the formulary.

But at Indiana University Health in Indianapolis, a different projection led to a decision to exclude the biosimilar from the formulary, said Jennifer Reddan, director of the organization's Center for Medication Management.

Reddan said that limiting the formulary's filgrastim to two Amgen products—Neupogen and Neulasta, a pegylated filgrastim formulation—is the best financial option for the health system, for now.

"With our system contract and our significant use of pegfilgrastim in the outpatient setting, it was not cost-beneficial for us to use or convert away from the Neupogen, because it impacts our pegfilgrastim pricing," Reddan explained.

Lisa Bendz, clinical pharmacist at the Center for Medication Policy at Duke University Hospital in Durham, North Carolina, said her health system completed a full review of the filgrastim class and opted to retain Neupogen and Neulasta on the formulary.

"We looked at the efficacy, safety, and cost," Bendz said. "We considered these all therapeutically equivalent, and the final decision came down to efficacy in special patient populations as well as costs."

Biosimilars

FDA approved Zarxio last year as a biosimilar version of Neupogen. Another filgrastim product, Teva's Granix, was approved in 2012 through FDA's standard licensing process and is not considered a biosimilar.

The agency this year approved biosimilar versions of infliximab, etanercept, and adalimumab, none of which are available yet on the U.S. market.

"I think everyone is hoping that there will be opportunities for cost savings with biosimilars," Bendz said. "Hopefully, this will also improve patient access to these high-cost medications."

Janet Woodcock, director of FDA's Center for Drug Evaluation and Research, said in written testimony this past February that the agency is working with manufacturers of 59 proposed biosimilar products for 18 different reference biologicals.

Biosimilars, in theory and by statute, come in two official types: those that are interchangeable and those that are biosimilar.

A biosimilar must be highly similar to its reference product, with only minor differences in clinically inactive components and no clinically meaningful differences in safety, purity, and potency.

An interchangeable product must meet all biosimilarity criteria and is expected to produce the same clinical result as the reference product in any patient.

Manufacturers must decide whether to apply for approval of their products as biosimilar or interchangeable. But FDA hasn't finalized its guidance for industry on interchangeability, and no product designated as interchangeable has been approved by the agency.

Evaluation and Use

Reddan said members of her hospital's pharmacy and therapeutics committee were briefed on biosimilars but decided not to develop a unique policy for the products.

"They basically said, 'We're comfortable with them being considered generic equivalents,...so you guys make the adjustments and make the decisions,'" Reddan said.

Pickette said his medical center's first-ever evaluation of a biosimilar product wasn't straightforward and took longer than usual.

For inpatient use, he said, the clear decision was to use Zarxio, which was "the lowest-cost agent."

"However, in the ambulatory [care] setting, it depended on the patients' insurance. So we left the other agents available for use" in ambulatory care clinics, he said.

But even on the inpatient side, a snag arose because of differences in the filgrastim products' packaging that affect their use.

Zarxio and Granix are available only in single-dose syringes. Neupogen is available in vials as well as single-dose syringes.

"For large doses that we use for stem-cell mobilization in the oncology setting, the patient would have to receive five shots" from a prefilled syringe, Pickette explained. Instead, these patients receive Neupogen, which can be prepared from multiple vials and administered as a single injection.

He said Neupogen is used when a filgrastim dose greater than 960 µg is required, in patients with latex allergy, in neonates, and in pediatric patients who require doses less than 300 µg or more than 480 µg.

Pickette said after the decision was made to use both Zarxio and Neupogen, an unexpected technological hurdle arose.

"One of the interesting things about implementing this interchange is that our electronic health record program couldn't distinguish between the two. It saw them as AB-rated interchangeable because they're both filgrastim. So we had to actually make modifications to distinguish them, because we were splitting hairs about who gets what," he said. "It's not clean; it's not easy."

And he said decisions about when to use Zarxio have been affected by resistance among the medical center's hematologists and oncologists—specifically, their "reluctance to use it for anything outside of the approved indications."

Zarxio shares five labeled indications with Neupogen but, unlike Neupogen, is not indicated for urgent administration to increase survival in patients acutely exposed to myelosuppressive doses of radiation. The labeling for Granix, or tbo-filgrastim, which is also on the formulary, has just one indication.

Pickette said the filgrastim discussion reminded him of what occurred years ago when dalteparin entered the market as a competitor to enoxaparin, the first FDA-approved low-molecular-weight heparin.

"There was no evidence to say that they were any different," Pickette said of the anticoagulant drugs. "But we still had to convince everybody that they were OK to interchange. So it's a lot of perception, a lot of education."

Reddan noted that similar perceptions at her institution have affected the acceptance of biosimilars.

"We've not been able to treat them like generics even though we're able to evaluate them similarly to how we would evaluate a generic equivalent," she said.

The Next Time

Reddan said the pharmacy staff keeps abreast of the biosimilars landscape in order to prepare to evaluate new products as they become available.

And she's discussed biosimilars with the hospital's director of purchasing so that he will be ready to handle any information technology issues related to acquiring the products.

Reddan said products biosimilar to infliximab are likely to be of particular interest at the hospital. Pickette said he's "very excited" about the prospect of a biosimilar version of rituximab entering the U.S. market.

But Bendz cautioned that until review teams gain more experience evaluating biosimilars, the arrival of new products could be a mixed blessing.

"One of our concerns, from our first experience, is having to review a class multiple times because of staggered entries of biosimilars into the market, as well as a lot of price negotiations, which may change formulary decisions," Bendz said. "So we're trying to get ahead of that, and we're starting to think about ways we can abbreviate the process if necessary. But I think that won't come until we've [reviewed] a few and everyone feels comfortable."

[This news story appears in the Nov. 15, 2016, issue of AJHP.]

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