Name:
Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn’s disease (VOLTAIRE-CD): a multicenter, randomized, double-blind, phase 3 trial
Description:
Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn’s disease (VOLTAIRE-CD): a multicenter, randomized, double-blind, phase 3 trial
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T00H13M20S
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Upload Date:
2023-06-13T00:00:00.0000000
Transcript:
Language: EN.
Segment:1 Introduction.
[MUSIC PLAYING]
STEPHEN HANAUER: My name is Professor Stephen Hanauer from the Feinberg School of Medicine at Northwestern University, and I am the lead author of the manuscript entitled "Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn's disease the VOLTAIRE-CD study, a multicenter, randomized, double-blind phase 3 trial", which was published in The Lancet Gastroenterology and Hepatology. On behalf of my co-authors, I am pleased to present the results from the VOLTAIRE-CD study, which aim to compare the efficacy and safety of BI 695501 with adalimumab reference product in patients with Crohn's disease.
Segment:2 What was the purpose of this study?.
STEPHEN HANAUER: Crohn's disease is a chronic inflammatory condition affecting the digestive tract that can cause abdominal pain, fever, diarrhea, and the passage of blood or mucus. Biologics that target tumor necrosis factor-alpha, such as the monoclonal antibodies infliximab and adalimumab, have greatly improved the management of patients with Crohn's disease who are not responding to initial therapy with corticosteroids, thiopurines, or methotrexate.
STEPHEN HANAUER: However, these drugs remain expensive. Biosimilars have the potential to increase the number of patients able to benefit from biologics, primarily by decreasing the treatment costs. The additional interchangeable designation allows a biosimilar to be substituted without the intervention of the health care professional who prescribed the reference product.
STEPHEN HANAUER: BI 695501 is a US FDA approved interchangeable biosimilar to adalimumab reference product. Bioequivalence between BI 695501 and adalimumab reference product has been previously demonstrated in a study of healthy volunteers in which the primary endpoints were pharmacokinetic parameters.
STEPHEN HANAUER: BI 695501 has also demonstrated similar efficacy, safety, and immunogenicity to adalimumab reference product in patients with rheumatoid arthritis and chronic plaque psoriasis. The VOLTAIRE-CD study aimed to compare the efficacy and safety of 695501 to adalimumab reference product in patients with Crohn's disease.
Segment:3 How was the study undertaken?.
STEPHEN HANAUER: VOLTAIRE-CD was a phase 3 multicenter, double-blind, parallel group, active comparator trial which was conducted at 92 treatment centers across countries in Europe and the USA. Patients were aged 18 to 80 years, with moderate to severely active Crohn's disease. This was defined as a Crohn's disease activity index score between 220 and 450 with confirmed endoscopic or radiological evidence of mucosal ulceration for longer than four months. Patients were also either naive to anti-TNF therapy or were previously treated with infliximab and had developed secondary resistance.
STEPHEN HANAUER: Doses of BI 695501 and adalimumab reference product were 160 milligrams on day one and 80 milligrams on day 15, followed by 40 milligrams every two weeks by subcutaneous injection. Patients with a decrease from baseline in the Crohn's disease activity index of at least 70 points at week four were classified as responders and were eligible to continue receiving study treatment. At week 24, patients in the adalimumab reference product group were scheduled to switch to BI 695501. Whereas those in the BI 695501 group received the same product throughout.
STEPHEN HANAUER: The primary endpoint was the proportion of patients with a clinical response at week four. This was defined as a decrease from baseline in the Crohn's disease activity index score of at least 70 points. Secondary efficacy endpoints were the proportion of patients with clinical response and the proportion of patients with clinical remission, which was defined as a Crohn's disease activity index score of less than 150 at week 24.
STEPHEN HANAUER: Secondary safety endpoints included the proportion of patients with adverse events, serious adverse events, adverse events of special interest, and injection site reactions. An exploratory noninferiority margin of 0.76 for the lower limit of the two-sided 90% confidence interval of the risk ratio was used for the primary analysis.
STEPHEN HANAUER: This analysis was conducted in a modified full analysis set of all patients who received at least one dose of study medication and had a baseline and at least one post-baseline Crohn's disease activity index assessment.
Segment:4 What were the results?.
STEPHEN HANAUER: In the primary endpoint analysis, the proportion of patients with the clinical response at week 4 was 90% in the BI 695501 group and 94% in the adalimumab reference product group. In an exploratory analysis, clinical response rates at week 4 remained similar between the groups after model adjustment for covariates. The rates were 88% in the BI 695501 group, and 93% in the adalimumab reference product group, with a risk ratio of 0.945. The associated 90% confidence interval was 0.870 to 1.028. This exploratory analysis indicated that BI 695501 is noninferior to adalimumab reference product because the lower limit of the 90% confidence interval for the risk ratio was above the prespecified threshold of 0.76.
STEPHEN HANAUER: Data for the two secondary efficacy endpoints were similar between treatment groups. After model adjustment for covariates, the risk ratio for week 24 for clinical response was 1.00. Additionally, the risk ratio for clinical remission was 0.900. The confidence intervals both contained one for these analysis, and there were no significant between group differences.
STEPHEN HANAUER: The mean CDAI, Crohn's disease activity index, scores in both treatment groups decreased markedly between baseline and week 4. Showing further small reductions at weeks 12 and 24. These results are shown in the figure. Overall, reductions versus baseline were similar in the two treatment groups.
STEPHEN HANAUER: In the safety analysis set, the safety profiles of BI 695501 and adalimumab reference product were similar, as shown by treatment emergent adverse events incidents from baseline to week 24. Results from study weeks 24 to 56 showed that BI 695501 was similarly well-tolerated in patients receiving BI 6955001 throughout the study as in those switching from adalimumab reference product to BI 695501.
STEPHEN HANAUER: The incidence of anti-adalimumab antibody formation was numerically higher in the BI 695501 group than the adalimumab reference product group at baseline, week 4, week 24, and week 48. However, across both treatment groups, the titers were generally low and were not considered clinically meaningful. When we compare the incidence of pharmacokinetically relevant antidrug antibodies, defined as a titer of greater than or equal to 256, the two treatment groups showed a similar incidence, confirming the observed similarity in the efficacy pharmacokinetics and safety over 48 weeks.
Segment:5 What is the significance of these findings?.
STEPHEN HANAUER: These results show similarly high clinical response rates among patients with Crohn's disease treated with either BI 695501 or adalimumab reference product. The exploratory analysis of the Crohn's disease activity index rates at week 4 indicated that BI 695501 is non-inferior to adalimumab reference product. Overall safety results were similar between the two treatment groups. Patients switching from adalimumab reference product to BI 695501 showed no reduction in efficacy and no increase in the incidence of adverse events.
STEPHEN HANAUER: Numerically higher proportions of patients who received BI 695501 throughout the study tested positive for antidrug antibodies compared to patients who received adalimumab reference product followed BI 695501. However, post-hoc analysis indicated that a similar proportion of patients in both groups had clinically relevant antidrug antibodies with a titer greater than or equal to 256.
STEPHEN HANAUER: The similar efficacies and pharmacokinetics of BI 695501 and adalimumab reference product reported here are consistent with earlier comparisons of the two drugs in patients with rheumatoid arthritis and chronic plaque psoriasis. The finding supports the principle of extrapolation, which, for BI 695501, enabled its approval across seven adalimumab reference product indications, including Crohn's disease. [MUSIC PLAYING]
