By Marilynn Larkin
NEW YORK (Reuters Health) - Colony-stimulating growth factors (CSF) biosimilars filgrastim-sndz and filgrastim-tbo are comparable in terms of safety and efficacy to the reference drug (Neupogen and other brand names), researchers say.
"Equivalency in efficacy and safety of biosimilar and originator products cannot be assumed," Dr. Abiy Agiro of HealthCore Inc. in Wilmington, Delaware, told Reuters Health by email. "The FDA's abbreviated approval pathway does not require a randomized clinical trial comparing biosimilar products to the reference drugs."
However, he added, "even if randomized clinical trials showed no clinically meaningful difference between biosimilar and originator products, real-world results could differ. Since equivalence cannot be inferred without additional post-approval observational studies, healthcare providers, pharmacies, and health insurers still have concerns regarding the use of biosimilar drugs."
Dr. Agiro and colleagues studied 11,202 commercially insured adults at risk for chemotherapy-induced neutropenia who received reference or biosimilar filgrastim from September 2012 through April 2017.
As reported online November 1 in JAMA Oncology, half the participants were older than 61, 62% were women, and 1,531 (13.7%) used biosimilar CSFs.
No significant differences in baseline risk factors were seen between the reference and biosimilar groups. Biosimilars accounted for 7% of filgrastim users in 2014, 16% in 2015, and 36% in 2016.
With respect to febrile neutropenia (FN), incidence rates for strict (neutropenia and fever) and broad (neutropenia or fever) definitions were similar in both groups: 11% for biosimilars and 9.4% for brand-name drugs. For strict FN specifically, incidence rates were 4.5% for the biosimilar group and 3.9% for the brand-name group.
Adverse events rates were similar: 6.9% for biosimilars and 6.4% for brand-name drugs.
Mean drug costs also were similar: $2,522 for biosimilars and $2,516 for brands. However, the daily cost was 2.3% less for biosimilars: $731 versus $748.
Average total costs per patient and per day of use, respectively, were marginally higher for tbo-filgrastim: 2.7% versus 2.3% for the reference drug. The authors say savings have been "modest" with biosimilars because early adoption has been slow; therefore, current pricing closely tracks that of the brand-name products.
"A real-world post-approval analysis like ours should be conducted for every biosimilar product that is approved in the U.S.," Dr. Agiro said. "Demonstrating similarity in efficacy and safety will increase the interchangeability of biosimilar and originator products."
"Our results show increased uptake of biosimilar filgrastim, which we anticipate will rise even more with evidence from studies like ours reassuring stakeholders," he concluded.
Dr. Roy Browne, Director, Oncology Pharmacy Services at Montefiore Health System in New York City, agreed with the findings. However, he said by email, "technically tbo-filgrastim is not a biosimilar as it was not approved using the biosimilar pathway. It was approved with the NDA (new drug application) pathway...with only one indication and still only has one indication as far as I know."
"Neupogen currently has six indications," he told Reuters Health. "Use of tbo-filgrastim would require a practitioner to have reviewed any existing data and find it equivalent for the other five indications before using it outside of its singular indication. This process slows adoption."
Often, he noted, insurers or pharmacy benefit managers (PBMs) "dictate what agents they pay for. It would have been helpful in this study to see the categorization of insurances for the different patients, and for us to know if substitutions were allowed...It would be important to know if insurers or PBMs influenced which product patients would receive."
With regard to the influence of insurers, Dr. Eyal Meiri, Interim Chief of Medical Oncology at Cancer Treatment Centers of America in Atlanta, Georgia, said, "Clinicians today are using biosimilars because the commercial carriers are requesting they be used preferentially."
"Future studies are needed to determine the best strategy to employ in utilizing biosimilars," he said in an email to Reuters Health. "Insurers should participate in studies proving the hypothesis that a biosimilar is more cost-effective than a brand name."
Dr. Zvi Loewy, Immediate Past Dean, Touro College of Pharmacy in Staten Island, New York, commented by email, "Much progress has been made in the broad field with several biosimilars."
However, the current study "falls short," he said, "because it did not address immunogenicity, pharmacokinetics and pharmacodynamics - the data need to determine efficacy."
The study was funded by Anthem. One author is an employee; he and another author own stock in the company.
JAMA Oncol 2018.