The FDA’s approval this month of the first U.S biosimilar, Zarxio from Sandoz, has formally opened the floodgates for sponsors seeking approval of lower-cost biologics to compete with expensive brand-name prescription drugs.
Already, the FDA is working with sponsors on the development of 50 biosimilars of 15 different branded or reference biologics.
“In terms of the FDA meeting the challenges ahead we are very positive, having created a robust review program that has generated interest in biosimilars,” said Leah Christl, Ph.D., the FDA’s associate director for therapeutic biologics, part of the Center for Drug Evaluation and Research (CDER).
She said biosimilar approvals can take 10 months and include a series of FDA-mandated development steps, criteria evaluations and clinical trials to ensure safety and efficacy closely matches the reference drug.
Zarxio is a close copy of Neupogen from Amgen, a treatment for chemotherapy patients to boost blood cells that help them fight off infections from cancer. The biosimilar, which is allowed to carry nearly identical labeling language to Neupogen, has been approved and on the market in Europe since 2009, after Amgen’s U.S. patent expired. Overseas, Zarxio sells for 20% to 30% less than Neuopogen.
In January, an FDA advisory panel unanimously recommended the agency approve Zarxio, sending the signal to other biosimilar developers to ready their applications.
“The biological products tend to be products that have very high prices,” John K. Jenkins, M.D., director of the Office of New Drugs at CDER, said in a call with reporters. “With competition, one of the goals is to hopefully see lower prices to make access better for patients who need these products.”
With Zarxio’s entry into the U.S. market, Express Scripts, the nation’s largest prescription benefit manager, estimated a $5.7 billion savings in drug costs over the next 10 years. It also estimated $250 billion in drug costs could be saved over the next decade if 11 biosimilars, in various stages of development, are approved. These include biosimilars of blockbuster reference drugs Remicade (Janssen) and Humira (AbbVie), both anti-inflammatories, and Herceptin and Avastin (both from Genentech), both cancer medications. The savings from the biosimilar pathway is likely to grow significantly greater once an additional set of major biologic drug patents expire between 2026 and 2028.
Research group IMS Health estimates low-cost versions of biotech drugs will account for 4% to 10% of the global $250 billion forecast to be spent on biologics by 2020.
“This (Zarxio) approval is good news for the entire healthcare system and brings us one step closer to making the important medications available for the patients who need them,” Sumant Ramachandra, Ph.D., senior vice president, R&D, medical & regulatory affairs at Hospira, said in a statement.
Hospira, soon to be a subsidiary of Pfizer, has two biosimilar applications currently under FDA review and in Europe and Australia has been marketing biosimilars for five years that sell for up to 30% less than the name-brand biologics they copy.
In the U.S., the actual savings could depend on the FDA’s future regulatory decisions, including whether biosimilars will share the generic name of the drugs they copy, which would benefit the name recognition of biosimilars. For example, the generic name for Neupogen is filgrastim. To separate the biosimilar version, the Sandoz label says filgrastim-sndz, the suffix standing for the manufacturer, which identifies it as a biosimilar version of Neupogen. However, the Sandoz example is not a general policy for biosimilar naming.
Another issue requiring further FDA guidance is “interchangeability,” which also could lead to greater acceptance of biosimilars. Christl explained that Zarxio is an approved biosimilar but is not interchangeable, because patients must communicate with their insurers and/or physicians for permission to bypass the branded drug.
“Physicians can write a prescription for biosimilars just like any other drug product, but if the brand name is specified, their patients cannot automatically substitute it at the pharmacy level,” said Christl. “The pharmacy has to contact the prescriber for permission to switch to the biosimilar, and if the pharmacist receives an okay from the physician only then can the substitution be made.”
However, Christl cautioned that the FDA has not issued guidance on interchangeability. Sandoz could return to the FDA seeking interchangeability status with additional data from a clinical trial that shows taking the biosimilar and alternating it with the brand drug virtually had identical results and no difference in safety or effectiveness.
“We’re giving advice to improve interchangeability requirements,” said Christl, explaining that generic products can be substituted easily because they are replicas of the brand-name small molecule medicines that are chemically synthesized.
Biologics, however, are more complex than traditional drugs, as they are made from living organisms, so they cannot be replicated precisely by another product. Thus, biosimilars are viewed as copycat products that are similar enough in safety and effectiveness.
In outlining its approval of Zarxio, the FDA stressed there was very little clinical difference compared to Neupogen.
“We did not see any differences that would suggest there would be any situations where a prescriber would have to choose one or the other based on safety and efficacy,” said Jenkins of the FDA. “They should perform the same.”
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