A research poster presented by at the Academy of Managed Care Pharmacy Annual Meeting, held March 27-30 in Denver, Colorado, explored the effectiveness and safety outcomes of the branded and biosimilar versions of filgrastim in a real-world comparative study.
Sandoz, the maker of a biosimilar version of filgrastim-sndz sold as Zarxio, has been locked in legal battles with Amgen, manufacturer of the branded filgrastim sold as Neupogen, for almost 2 years. A Supreme Court decision on the “patent dance” fight is expected by this June, but in the meantime, researchers have continued to investigate whether the drugs are clinically equivalent.
In randomized trial settings, filgrastim-sndz has demonstrated a high degree of similarity to the reference drug with no clinically meaningful differences in effectiveness. The drugs are granulocyte-colony stimulating factors (G-CSFs), which work to prevent chemotherapy-induced febrile neutropenia by imitating natural proteins that spur neutrophil production in the bone marrow. Febrile neutropenia was defined as hospitalization with a diagnosis of infection and/or neutropenia, within 14 days post-index (broad definition). The narrow definition was hospitalization with a diagnosis of infection and neutropenia within 14 days post-index.
Although randomized trials have demonstrated equivalent outcomes sufficient for FDA approval, a group of researchers from Humana decided to investigate the real-world effectiveness and safety outcomes of filgrastim and filgrastim-sndz, as well as pegfilgrastim, which is another G-CSF sold as Neulasta by Amgen. The researchers used administrative claims data from the Humana Research Database of around 19 million patients enrolled in commercial or Medicare plans.
Beneficiaries with medical and pharmacy coverage were included in the study if they had a claim for a G-CSF during the study period and had received chemotherapy within 6 days prior to the G-CSF claim. The research outcomes were the incidence of neutropenia, using both the broad and the narrow definitions, and the incidence of adverse events, defined as a claim for spleen rupture, acute respiratory syndrome, serious allergic reaction, capillary leak syndrome, thrombocytopenia, leukocytosis, cutaneous vasculitis, or bone and muscle ache.
The researchers determined that filgrastim and filgrastim-sndz had less than a 1% difference in the incidence of febrile neutropenia, using both the broad and narrow definitions. This small difference in incidence combined with a confidence interval that crossed 0 indicated statistical equivalence. The incidence of adverse drug events, however, was higher among the patients with claims for filgrastim-sndz (5.9% vs 3.4%).
In a separate analysis comparing filgrastim to pegfilgrastim, which has greater bioavailability, the researchers found that the only measure for which the 2 drugs were equivalent was the narrower definition of febrile neutropenia, which required the presence of both infection and neutropenia—patients taking pegfilgrastim had significantly higher rates of adverse medication events (5.8% vs 3.4%) and febrile neutropenia when defined broadly as infection and/or neutropenia (6.8% vs 3.4%).
The study authors concluded that this real-world evidence does not necessarily support equivalence between branded filgrastim and the biosimilar or the newer pegfilgrastim. They acknowledged, however, that the study group sizes were imbalanced and they could not control for differences in cancer type or chemotherapy exposure, which could have accounted for some of the variability in outcomes.
“The study findings should be interpreted in context given that chemotherapy regimens vary based on patient and cancer type/stage,” the poster explained.
The researchers also indicated that they could not include tbo-filgrastim, sold by Teva as Granix, in the statistical comparison due to low sample sizes in the claims database. Tbo-filgrastim’s approval predated the initiation of the FDA’s biosimilar approval pathway, so it is not technically considered a biosimilar, but it has demonstrated comparable safety, efficacy, and pharmacokinetic activity to the branded version of filgrastim.
Douglas AG, Schwab P, Lane D, Kennedy K, Slabaugh L, Bowe A. A comparison of brand and biosimilar granulocyte-colony stimulating factors for prophylaxix of chemotherapy-induced febrile neutropenia. Presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2017, Denver Colordao.