Biogen announce new daclizumab data at the 68th Annual Meeting of the American Academy of Neurology (AAN) in Vancouver, Canada. The data demonstrate daclizumab’s positive cognitive outcomes, targeted and reversible mechanism of action (MOA), and safety profile in patients with relapsing-remitting multiple sclerosis (RRMS).1,2,3
Sustained cognitive outcomes achieved with daclizumab
Data presented from the Phase III DECIDE study highlight the positive, sustained impact that daclizumab may have on cognitive function for patients with RRMS, in particular processing speed and attention. Cognitive impairment is a common symptom of MS affecting 43–70% of patients and causes significant functional disability, as well as decreased quality of life.4 Cognitive decline in MS can involve memory impairment, slowed information-processing speed (including difficulty following conversations or multitasking), impaired executive function (including difficulty with organisation or planning), and visual / spatial-processing (including difficulty with right-left orientation or navigation).5,6
In the multi-centre, double blind, active-controlled, Phase III study of 1841 patients, cognitive improvements were measured using the Symbol Digit Modalities Test (SDMT – a measure of information-processing speed and attention), across a daclizumab group and an intramuscular (IM) interferon beta-1a group. Improvements in SDMT ≥3 points or ≥4 points are deemed to be clinically meaningful.7
Clinically meaningful improvements in SDMT scores (≥3 points, ≥4 points) were observed in a higher percentage of patients receiving daclizumab versus interferon beta-1a IM at week 96 (60% versus 51.4% respectively for ≥3 point improvement (P=0.0153), and 55.4% versus 50.1% respectively for ≥4 points (P=0.0366)). These improvements were sustained at week 144 (65.5% vs 52.0% respectively for ≥3 point improvement (P=0.0028), and 61.7% versus 48.4% respectively for ≥4 points (P=0.0067)).1 Mean improvements from baseline at week 144 as measured using the SDMT were +6.30 for daclizumab-treated patients versus +3.09 for interferon beta-1a IM-treated patients (p=0.0024).1
Daclizumab targeted MOA supports safety profile
Daclizumab selectively modulates interleukin-2 receptor signalling, leading to selective antagonism of pro-inflammatory effector T-cell activity and increased numbers of immune-regulatory CD56 natural killer (NK) cells. Data presented from the SELECT and SELECTION studies demonstrated that decreases in total, and differential, lymphocyte counts during treatment were modest and reversible upon treatment discontinuation. The CD4+/CD8+ ratio remained stable in SELECT and SELECTION. The absence of profound depletion of total lymphocytes, CD4+ and CD8+ T cells, and CD56 NK cells during treatment, and the reversibility of the changes in cell counts, provide further evidence of the targeted immunomodulatory MOA of daclizumab in RRMS.2
Additional data presented from the DECIDE study assessed cutaneous adverse events (AEs) associated with daclizumab. The majority (94%) of AEs observed were mild or moderate.3 The rate of serious AEs remained low at 2%, and were resolved following topical and/or systemic steroids, antihistamines, other therapies or treatment discontinuation. These data highlight that although serious AEs were infrequent, physicians should be aware that these events can occur and may need to be managed with multiple therapies.3
- Benedict et al. Improved cognitive outcomes in relapsing-remitting multiple sclerosis with daclizumab in the phase 3 DECIDE study. P090. The 68th Annual Meeting of the American Academy of Neurology (AAN), Vancouver, Canada, 15–21 April 2016. Accessed April 2016.
- Fam et al. Reversible effects of daclizumab on lymphocyte counts in RRMS patients: data from the SELECT Trilogy studies. P5.281. The 68th Annual Meeting of the American Academy of Neurology (AAN), Vancouver, Canada, 15–21 April 2016. Accessed April 2016.
- Ford et al. Experience with serious cutaneous events in the DECIDE study. P2.083. The 68th Annual Meeting of the American Academy of Neurology (AAN), Vancouver, Canada, 15–21 April 2016. Accessed April 2016.
- Mitolo et al. Cognitive rehabilitation in multiple sclerosis: A systemic review. J Neurol Sci 2015;354(1–2):1–9.
- Multiple Sclerosis Society. Cognitive dysfunction in multiple sclerosis. Available at: www.mssociety.org.uk/what-is-ms/signs-and-symptoms/memory-and-thinking/cognitive-problems. Accessed April 2016.
- National MS Society. Cognitive dysfunction in multiple sclerosis. Available at: www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Clinical_Bulletin_Cognitive-Dysfunction-in-MS.pdf. Accessed April 2016.
- Benedict et al. Characterizing cognitive function during relapse in multiple sclerosis. Mult Scler 2014;20(13):1745–52.