A retrospective, postmarketing study demonstrates higher incidence of joint and bone pain, neutropenia with certain filgrastim biosimilars, compared with Neupogen.
Editor's Note: Since publication of this article, the findings in the study by Rastogi S et al referenced below have been criticized as having been based on poor scientific methodology. Reliance upon data from the VigiBase adverse event database of the World Health Organisation, which is not intended for the testing of medical hypotheses, is one of the criticisms leveled against this study. The Center for Biosimilars® is preparing a follow-up article on this issue.
A new study has associated a higher incidence of certain adverse events with the filgrastim biosimilars, Zarzio, Grasin, Nivestim, and Tevagrastim compared with the reference product Neupogen.
These biosimilar products are marketed outside the United States under these brands and have US equivalents.
Filgrastim was originally approved in 1991 for the treatment of patients with cancer who are receiving myelosuppressive chemotherapy. It was subsequently approved for multiple oncology related indications and severe chronic neutropenia. Multiple filgrastim biosimilars have been approved in the United States, Europe, and elsewhere since 2008.
The retrospective, postmarketing study comprised data from 1991 to May 2018 from VigiBase, a World Health Organization database of adverse events information. VigiBase is often used to aid postmarket studies.
Distribution of Adverse Events
Investigators identified 11,183 adverse drug reaction reports, of which 51.5% (5764) were related to Neupogen, the originator. Leucostim had 680; Zarzio, 622; Grasin, 545; Nivestim, 359; and Tevagrastim, 152.
Grasin was associated with higher reporting of pyrexia, or fever, compared with neupogen (11.5% vs 7.9%, reporting odds ratio [ROR] 1.52); myalgia, or muscle pain, (37% vs 2.2%, ROR 25.94); and back pain (11.3% vs 4%, ROR 3.09).
Findings showed that Zarzio was associated with increased reporting of arthralgia, also known as joint pain (4.5% vs 2.9%, ROR 1.59). Zarzio also had higher reporting of neutropenia, or low white blood cell count (11.4% vs 4%, ROR 2.59).
Bone pain was reported more often for Nivestim than reference filgrastim (14.4% vs 8.3%, ROR 1.87).
Drug ineffectiveness was reported in cases with Zarzio (35.9%), Nivestim (19.4%), and Tevagrastim (42.2%).
Efficacy Differences Also Observed
The authors also observed significant differences between the originator and biosimilars in regard to efficacy, adverse events reported, and time to onset of occurrences.
They stressed that epidemiologic studies are needed to confirm these findings and provide additional insights.
Zarzio is owned by Sandoz and is marketed is as Zarxio in the United States. Grasin is owned by Teva Pharmaceuticals Japan and is marketed in Republic of Korea. Tevagrastim is marketed in Europe and is owned by Teva Generics GmbH, a Teva Pharmaceuticals company. Tevagrastim is marketed as Tbo-filgrastim in the United States. Nivestim is owned by Pfizer and is marketed as Nivestym in the United States.
Leucostim is marketed in Peru, the Republic of Korea, and Turkey.
In the United States, the FDA recently launched the FDA adverse Event Reporting system (FAERS). FAERS is a public search engine for drugs and biologics and contains adverse event reports submitted by healthcare providers, consumers, manufacturers of drugs and biologics, and other stakeholders.