Melissa Dillmon, MD
The FDA’s approval in March of the first biosimilar drug for the US market has aroused much concern among physicians, who fear that these complex drugs will not be perfect substitutes for the branded drugs they will replace and who insist that certain standards be attached to their approval and distribution.
“There is no doubt that biosimilars will play a large role in the future treatment of our patients, and hopefully that they will fulfill their goal of bioequivalence and decreased cost,” said Hillary Hahm, MD, a medical oncologist with Northwest Georgia Oncology Centers and also a board member of the Georgia Society of Clinical Oncology (GASCO). “However, there need to be safeguards concerning the development and clinical use of each of agents, so that our patients are assured the best possible treatment from both an efficacy and safety standpoint.”
Georgia is one of at least 23 states so far whose legislatures have considered regulating the prescription, doctor and patient notification, recordkeeping, and approvals of biosimilars. GASCO has sought to block legislation in Georgia that would allow Georgia pharmacists to dispense biosimilar drugs as a substitution for brand name drugs without physicians being informed about the substitutions.
Melissa Dillmon, MD, president of GASCO and a medical oncologist at the Harbin Clinic in Rome, Georgia, is pushing for a requirement that pharmacists notify physicians and patients about potential biosimilar substitutions. “The patient has to know they are not getting the same thing, and the physician has to be notified,” said Dillmon, adding that the US has no track record on researching the safety and efficacy of biosimilars.
Biosimilars—complex molecule drugs that are administered intravenously—have been marketed in Europe since 2007, and they are now entering the US via a pathway established by The Biologics Price Competition and Innovation Act of 2009, as part of the Affordable Care Act.1
The first FDA-approved biosimilar is Zarxio (filgrastim-sndz), a Sandoz drug that can boost white blood cell counts for cancer patients whose immune systems have been weakened by chemotherapy. The drug would compete with Amgen’s Neupogen, whose patent expired in December 2013.
There are legal obstacles to overcome before Zarxio is offered for sale. Amgen has challenged the sale of the drug, saying it was not given sufficient notice by Sandoz that the company was about to launch a biosimilar that would compete with Neupogen. In late March, a federal judge in San Francisco dismissed Amgen's claims, which led to an appeal in the US Court of Appeals for the Federal Circuit in Washington. This decision, which was handed down on May 5, blocked Zarxio from entering the market until oral arguments could be heard. The next court date is scheduled for June 3, 2015.
In granting approval, the FDA stated that Zarxio would not be regarded as “interchangeable” with Neupogen, despite its close similarity and “biosimilar” status.2
This means it cannot be substituted for Neupogen without the involvement of the prescribing physician. Much of the controversy surrounding biosimilars has to do with the variability of the manufacturing process of these large molecule drugs, which vary slightly from one batch to another in the same factory and also among batches produced by brand name manufacturers.
Many more biosimilars from Sandoz are on the way. Those that are undergoing or have completed clinical trials and are in line for FDA consideration include pegfilgrastim (comparable to Amgen’s Neulasta) for chemotherapy-induced febrile neutropenia; rituximab (comparable to Rituxan/MabThera) for patients with rheumatoid arthritis and follicular lymphoma; epoetin alfa (comparable to Johnson & Johnson’s Procrit and Eprex) for patients with anemia associated with chronic kidney disease; etanercept (comparable to Amgen’s Enbrel) for patients with plaque psoriasis; and adalimumab (comparable to AbbVie’s Humira) for patients with plaque psoriasis, according to Sandoz.An Ongoing Review of Pharmacy Laws
In contrast to generics, biosimilars aren’t perfect copies of brand name drugs, and as a result “all 50 states either have or will be reviewing their pharmacy laws about how to offer substitution,” predicts Mark Fleury, the policy principal of emerging sciences for the American Cancer Society Cancer Action Network (ACS CAN), a Washington, DC, group that advocates on behalf of patients. “Because all the existing laws are written for small molecules, not biosimilars, you can’t just apply the same law. The drugs are highly similar but may not be exactly the same. It boils down to the issues of consent and notification and what is considered interchangeable, and each state has to figure out how they want to handle it,” Fleury said.