Clinical Efficacy of Laquinimod for the Treatment of Multiple Sclerosis; Pooled Analyses from the ALLEGRO and BRAVO Phase III Trials (S01.007)

Vollmer, Timothy; Comi, Giancarlo; Sørensen, P. S.; Arnold, Douglas L.; Filippi, Massimo; Statinova, Olena; Kobys, Tetyana; Becker, Elke; Jeffery, Douglas; Montalbán, Xavier; Kappos, Ludwig; Boyко, Alexey; Selmaj, Krzysztof; Zipp, Frauke; Havrdová, Eva; Cohen, Jeffrey Jerome

doi:10.1212/wnl.78.1_meetingabstracts.s01.007

Cited by 5 publications

(3 citation statements)

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“…Two new oral therapies have recently been approved for the treatment of relapsing forms of MS: Dimethyl fumarate (BG-12, Tecfidera TM ) [Fox et al 2012;Gold et al 2012] and teriflunomide (Aubagio ® ) [O'Connor et al 2011], both having good safety profiles. Another oral agent, laquinimod, demonstrated only marginal efficacy in reducing relapse rate but was effective in reducing disability progression and the rate of brain atrophy and is very safe in RRMS [Vollmer et al 2012]. Alemtuzumab is soon expected to be approved after demonstrating superiority over SC IFNβ1a in both treatment-naïve and treatment experienced RRMS patients [Cohen et al 2012;Coles et al 2012].…”

Section: The Potential Role Of Daclizumab In the Treatment Of Msmentioning

confidence: 99%

The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis

Milo

2013

Ther Adv Neurol Disord

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Daclizumab is a humanized monoclonal antibody of the immunoglobulin G1 (IgG1) isotype that binds to the α-subunit (CD25) of the high-affinity interleukin-2 (IL-2) receptor expressed on activated T cells and CD4+CD25+FoxP3+ regulatory T cells. Based on the assumption that it would block the activation and expansion of autoreactive T cells that are central to the immune pathogenesis of multiple sclerosis (MS), daclizumab was tested in several small open-label clinical trials in MS and demonstrated a profound inhibition of inflammatory disease activity. Surprisingly, accompanying mechanistic studies revealed that the most important biological effect of daclizumab was rather a dramatic expansion and activation of immunoregulatory CD56 bright natural-killer (NK) cells that correlated with treatment response, while there was no or only minor effect on peripheral T-cell activation and function. These CD56 bright NK cells were able to gain access to the central nervous system in MS and kill autologous activated T cells. Additional and relatively large phase IIb clinical trials showed that daclizumab, as add-on or monotherapy in relapsing-remitting (RR) MS, was highly effective in reducing relapse rate, disability progression, and the number and volume of gadolinium-enhancing, T1 and T2 lesions on brain magnetic resonance imaging (MRI), and reproduced the expansion of CD56 bright NK cells as a biomarker for daclizumab activity. Daclizumab is generally very well tolerated and has shown a favorable adverse event (AE) profile in transplant recipients. However, several potentially serious and newly emerging AEs (mainly infections, skin reactions, elevated liver function tests and autoimmune phenomena in several body organs) may require strict safety monitoring programs in future clinical practice and place daclizumab together with other new and highly effective MS drugs as a second-line therapy. Ongoing phase III clinical trials in RRMS are expected to provide definite information on the efficacy and safety of daclizumab and to determine its place in the fast-growing armamentarium of MS therapies.

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Section: The Potential Role Of Daclizumab In the Treatment Of Msmentioning

confidence: 99%

The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis

Milo

2013

Ther Adv Neurol Disord

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“…In both of these placebo-controlled trials, laquinimod slowed the progression of disability and brain atrophy and reduced the rate of relapse in patients with RRMS. 58,59 An additional phase 3 trial (CONCERTO) will be initiated to further evaluate 2 doses of laquinimod (0.6 milligrams [mg] and 1.2 mg) in approximately 1,800 patients for up to 24 months and to confirm its utility in relapsing forms of MS prior to seeking FDA approval.…”

Section: Mechanism Of Action Of Current and Emerging Dmtsmentioning

confidence: 99%

Evaluating Risks, Costs, and Benefits of New and Emerging Therapies to Optimize Outcomes in Multiple Sclerosis

Bandari¹,

Sternaman²,

Chan³

et al. 2012

JMCP

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“…The BRAVO study did not achieve its primary endpoint of reducing the annualized relapse rate, but led to significant reduction in EDSS progression (34%) and brain volume loss (27%) [Teva Pharmaceutical Industries, 2011]. Pooled results from both trials were recently presented at the American Academy of Neurology, and showed that laquinimod had beneficial effects on ARR (21.4% reduction), disability progression (34.2% reduction), and brain volume (30% reduction) when compared with placebo [Vollmer et al . 2012].…”

Section: Emerging Therapiesmentioning

confidence: 99%

Benefits versus risks of latest therapies in multiple sclerosis: a perspective review

Ontaneda

Capua

2012

Therapeutic Advances in Drug Safety

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Disease-modifying treatments for multiple sclerosis (MS) have now been available for almost 20 years. Interferon β (IFN-β) products and glatiramer acetate (GA) were the first available options and are now considered first-line agents for the treatment of MS. These medications have several years of favorable safety data, but are not effective in completely controlling disease activity in all patients. Alternate medications with increased efficacy have been developed and identified; however, these newer medications have known or potential safety concerns which have prompted clinicians to view them as second-line agents. Highly efficacious and safe medications are continuously being searched for and developed; however, time is needed to establish the long-term safety of any new therapeutic agent. MS practitioners are faced with the clinical dilemma of treating patients with very safe modestly effective medications or using more efficacious and potentially riskier agents. The risk-benefit profile of every medication will have to be weighed carefully and clinicians will need to gage the risk tolerance of each patient in order to tailor treatment. This review will summarize benefits and risks of recently approved therapies in MS and will provide a perspective view on the placement of these medications within the MS treatment algorithm in the near future.

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Clinical Efficacy of Laquinimod for the Treatment of Multiple Sclerosis; Pooled Analyses from the ALLEGRO and BRAVO Phase III Trials (S01.007)

Cited by 5 publications

References 0 publications

The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis

The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis

Evaluating Risks, Costs, and Benefits of New and Emerging Therapies to Optimize Outcomes in Multiple Sclerosis

Benefits versus risks of latest therapies in multiple sclerosis: a perspective review

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