Adalimumab biosimilars on the horizon
medwireNews: A number of sessions at the Annual European Rheumatology Conference (EULAR) this year have focused on the efficacy and equivalence of biosimilars for the treatment of rheumatoid arthritis (RA); positive findings for two related to the anti-tumor necrosis factor (TNF) inhibitor adalimumab are reported here.
FKB327 shows therapeutic equivalency
Phase III study findings show therapeutic equivalency between FKB327, a proposed biosimilar of adalimumab, and the adalimumab reference product.
Among 728 patients with RA treated with 40 mg of either FKB327 or adalimumab subcutaneously every 2 weeks alongside methotrexate treatment for 24 weeks, there was no difference between the two treatment groups in the percentage of participants who met the American College of Rheumatology (ACR) 20 response criteria, at 74.4% and 75.7%, respectively.
Rieke Alten (University Medicine Berlin, Germany) pointed out to delegates in Madrid, Spain, that the primary study objective was “well reached,” with the 95% confidence intervals of –7.6 to 5.0% for the 1.3% treatment difference within the prespecified 13% equivalence margins.
The ACR20 response rates over time were also very similar, with curves closely overlapping from week 4 through to week 24.
The patients, from 105 sites in 12 countries, had all had moderate-to-severe active RA for at least 3 months before treatment. None of the patients had received prior treatment with adalimumab, but had received previous treatment with one biologic or TNF inhibitor for RA, but not with lack of efficacy in the case of the latter.
At baseline, there was a good balance between the two groups for demographic factors, RA characteristics, including disease duration, swollen and tender joint counts, and mean Disease Activity Score at 28 joints (DAS28), and prior biologic and concomitant medication use, with 18.1% having received a prior biologic and a third of patients taking both concomitant oral steroid and non-steroidal anti-inflammatory treatment for their RA.
In addition to ACR20 responses, ACR50 and 70 responses were comparable, at 49.0% and 21.3%, respectively, with FKB327 versus 49.4% and 25.1% with adalimumab. As was seen for the primary end point, the curves over time for the secondary endpoint of least squares mean DAS28 based on C-reactive protein (DAS28-CRP) closely overlapped and at week 24 the 0.1 point difference between the FKB327 and adalimumab groups was within the prespecified equivalence margin of 0.6.
The two drugs showed comparable immunogenicity at all timepoints, with 61.7% of patients in the biosimilar group and 59.1% of those in the adalimumab group positive for anti-drug antibodies at 24 weeks. There was a similar distribution of titers for the two groups and almost all antibodies were neutralizing.
Pharmacokinetics according to mean serum trough concentration–time profiles for adalimumab were broadly comparable between the treatment groups, as were serum trough concentrations at steady state.
Alten reported a similar safety profile for the two treatments, highlighting a very low discontinuation rate in both groups, of about 3%. One patient from Romania died from tuberculosis and this was considered possibly related to FKB327 treatment, otherwise the adverse events were as expected for adalimumab, such as respiratory tract infections and urinary tract infections, and low in numbers. Alten pointed out that there were three further cases of TB in the adalimumab group, and suggested this may be related to the condition being endemic to some of the countries in which data were collected.
Alten said that the findings show that “this phase III study was appropriately designed to demonstrate equivalence.” And she concluded: “Overall, these results demonstrate that FKB327 is a candidate biosimilar to adalimumab reference product.”
Further support for SB5’s biosimilarity
In a separate session looking at the immunogenicity of biologics, Jonathan Kay (UMass Memorial Medical Center,Worcester, Massachusetts, USA) presented findings showing comparable effects for adalimumab biosimilar SB5 and reference adalimumab as further support of the agents’ biosimilarity.
In previous findings the two drugs were found to be equally effective in the treatment of RA over a 24-week period, according to ACR 20, 50 and 70 response criteria.
Kay pointed out that for all the ACR responses, most notably ACR20 response, the timelines for the two drugs were totally superimposed, with multiple early timepoints, and the lines crossed each other, which he explains “is highly characteristic of biosimilarity.”
Kay added to these findings in his presentation reporting that the two drugs also had similar post-dose adalimumab serum trough concentrations.
In 356 patients taking 40 mg of either SB5 or adalimumab subcutaneously every other week for 24 weeks, serum trough concentrations ranged from 3.850 to 6.761 µg/mL in SB5-treated patients and from 3.892 to 6.773 µg/mL in patients taking adalimumab.
Using a previously reported optimal serum trough concentration cut-off point of 1.274 µg/mL for achieving a good EULAR response with adalimumab at 24 weeks, Kay and colleagues found that treatment was more effective in patients whose levels were at or above this level, compared with below, irrespective of whether they were taking SB5 or adalimumab.
Good EULAR responses were achieved at 24 weeks by 32.9% of SB5- and 43.2% of adalimumab-treated patients with serum trough concentration at or above 1.274 µg/mL, compared with a respective 23.8% and 26.9% of patients with lower levels.
A variety of other efficacy measures were also more favorable in patients with elevated serum trough concentration in both treatment groups, including DAS28, the simplified disease activity index, the clinical disease activity index, and ACR 20, 50, and 70 responses. Low disease activity according to the Simplified Disease Activity index was the only measure that was similar in patients with levels above and below the serum trough concentration threshold.
The likelihood of having a low serum trough concentration was greater among patients with detectable anti-drug antibodies, Kay reports, and this was the same for both SB5 and adalimumab. Almost all patients without anti-drug antibodies (ADA) had serum trough concentrations above the cutoff, at 100.0% and 97.4% of SB5 and adalimumab patients, respectively, compared with just over half of patients in each group with detectable ADA.
Kay concluded: “These findings further support the biosimilarity of SB5 to adalimumab complementing the efficacy and safety data that we demonstrated previously.”
By Lucy Piper
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