Biosimilars are poised to flood the U.S. pharmaceutical market, bringing biologic therapies within reach of many patients who previously could not pay for them. In a position statement issued last month, the American College of Rheumatology voiced its support for the new agents, but only if they are carefully regulated and tracked – and if prescribing decisions are left up to physicians and patients, not pharmacists or payers.
“As more biologic drugs are used to treat rheumatic diseases, rheumatologists are increasingly concerned about their high cost and patients being unable to afford them,” ACR president William St.Clair said in a written statement. “We agree that less-expensive biologic therapies are needed, and recognize that biosimilars provide an opportunity to reduce treatment costs.”
Dr. William St.Clair
The ACR position statement follows the U.S. Food and Drug Administration’s approval on March 6 of the first biosimilar, Sandoz’s Zarxio (filgrastim-sndz), which is used in cancer treatment and is based on Amgen’s Neupogen (filgrastim). Patents on many other biologics will expire by about 2020, clearing the way for biosimilars used in rheumatology, dermatology, and other fields. Among these, Celltrion’s infliximab biosimilar Remsima (CT-P13) was submitted for FDA approval last year for the treatment of rheumatoid arthritis, Crohn’s disease, and several other conditions. The FDA postponed a March 17 meeting to review Celltrion’s application, stating that it had requested more information from the company.
The ACR has echoed the FDA’s apparent caution regarding biosimilars. Although only the clinically inactive components of biosimilars are allowed to differ from their reference agents, today’s biologics are so molecularly complex that biosimilars need rigorous studies in humans to assess their safety and efficacy, the organization stated. “It is uncertain whether patients will respond to these drugs the same way they would to an original biologic, because biologics are very sensitive to manufacturing changes,” Dr. St.Clair said. “Even minor differences in a biosimilar’s molecular structure, purity, or other chemical properties could change the way a patient responds to the drug.”
Dr. Scott Zashin
For this reason, postmarketing studies in children and adults also will be essential, the ACR stated. Dr. Scott Zashin, a rheumatologist at Presbyterian Hospital, Dallas, and who is also with the University of Texas in Dallas, agreed. “Studies will need to be conducted to determine the benefit and risks,” he said in an interview. “In addition, registries would be needed to help assess long-term safety in larger numbers of patients than is feasible in a clinical trial.”
The ACR also raised concerns about switching patients back and forth between originator biologics and biosimilars, even if the biosimilar met stringent criteria demonstrating its interchangeability with the reference agent. “Experience outside the United States with biosimilar erythropoietin has indicated that a serious adverse reaction due to immunogenicity is a valid and very real concern for biosimilar products,” the ACR stated. “At this time, there are too many unknown variables to presume that repeated switching of biologic drugs would be safe practice.”
Because the FDA has not specified what would be needed to prove that a biologic and its biosimilar are truly interchangeable in the treatment of rheumatic conditions, pharmacists should not be allowed to substitute a biosimilar for a prescribed biologic without written approval from the physician, the ACR stated. But if pharmacists are legally allowed to substitute a biosimilar, they should be required to notify both physicians and patients so that patients can be monitored for adverse effects, the organization added.
Dr. Zashin agreed. “I would pretty much treat the biosimilars as generics, and leave it up to the FDA to decide if they are inferior,” he said. “But there are some generics on the market now (small molecules, not biologics) that I feel are inferior to the brand drug. This would be no different if biosimilars are approved.” For that reason, he would not accept a pharmacist substituting a biosimilar if he prescribed the branded drug, unless the patient preferred and specifically requested the less-expensive product, he said.
Along the same lines, the ACR believes that physicians should be able to designate a prescription as “brand only” if they are concerned about the safety of a biosimilar and that payers should not be able to force patients to switch to a biosimilar if they are already responding well to the biologic. But under current circumstances, “the insurance company would dictate what the patient could receive,” Dr. Zashin cautioned. If the patient refused the biosimilar, “I expect they would penalize the patient and make the brand quite costly.”