-- Study in 14 Patients Shows Eculizumab Significantly Reduced Frequency of Attacks in Patients with Severe Relapsing NMO --
NMO is a devastating, life-threatening, ultra-rare neurological disease that leads to severe weakness, paralysis, respiratory failure, loss of bowel and bladder function, blindness and premature death.2-4 In patients with NMO, uncontrolled complement activation causes destruction of myelin-producing cells, leading to severe damage to the central nervous system (CNS), including the spinal cord and optic nerve.5-7 Patients with NMO have a life-long exposure to the uncontrolled complement activation due to chronic autoimmune attack, and most patients experience an unpredictable, relapsing course of disease with cumulative disability, as each attack adds to the neurologic disability.3,8,9 Fifty percent of relapsing NMO patients have been reported to sustain permanent severe disability, including paralysis and blindness, within 5 years of disease onset.10 Most NMO-related deaths result from respiratory complications from NMO attacks10,11; in one report, 30% of patients died within 5 years of disease onset.10
Eculizumab is approved in over 40 countries as a treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH) and in the
"NMO is a debilitating and potentially life-threatening disease in which attacks of inflammation of the spinal cord and eye nerves can lead to paralysis, blindness, and death. If we can completely stop such attacks in NMO, we can prevent disability and provide patients the opportunity for significantly improved outcomes," said study investigator
"This investigator-initiated study suggests that eculizumab, by inhibiting the activation of terminal complement, blocks the underlying disease mechanism that leads to progressive and severe disability in patients with severe relapsing NMO," said
About the Study
The single-arm, open-label, Phase 2 trial was conducted at two
The study achieved its primary efficacy endpoint with high levels of clinical and statistical significance: a decline in the median annualized attack rate from three attacks per patient pre-eculizumab treatment to zero attacks per patient during 12 months of chronic eculizumab treatment (p < 0.0001). After 12 months of treatment, 86% (12 of 14) of these severely affected patients were completely attack-free. Two of the 14 patients had single "possible" relapses as reported by the study investigators. One of those two patients had back pain only less than 30 hours after the first dose of eculizumab, without clinical or radiological evidence of myelitis (inflammation of the spinal cord). The second of these two patients, while experiencing a urinary tract infection, also reported new onset of visual blurring (without pain) with reduction in visual acuity, which returned to baseline after intravenous immunoglobulin (IVIG) treatment. The study investigators suggested that this event might have actually been what they term a non-disease-related "pseudo-exacerbation."1
Eculizumab was associated with significant improvements in key secondary endpoints. The median expanded disability status scale (EDSS) score improved from 4.3 pre-treatment to 3.5 after 12 months of treatment with eculizumab (p < 0.01). Importantly, all patients experienced either improvement or stability in all key outcome measures, including EDSS, ambulatory function as measured by the Hauser Ambulation Index, and visual function as measured by visual acuity.1
Eculizumab appeared to be well-tolerated in the study, with the three most common adverse events being headache, nausea, and dizziness. One patient was successfully treated for a meningococcal sepsis infection and resumed eculizumab treatment within the trial. One patient died of a myocardial infarction (heart attack) approximately 4 months after completing treatment with eculizumab; this event was deemed unrelated to eculizumab. During the first three months following the protocol-specified termination of eculizumab treatment, two patients, while continuing to receive immunosuppressive treatment, experienced three severe relapses.1
About Neuromyelitis Optica (NMO)
Neuromyelitis optica (NMO, also known as Devic's disease) is a severe, ultra-rare neurological disorder characterized by chronic autoimmune attack leading to life-long exposure to uncontrolled complement activation that causes destruction of myelin-producing cells, leading to severe damage to the central nervous system (CNS), including the spinal cord and optic nerve.5-8,12 As a result, patients with NMO develop transverse myelitis (inflammation of the spinal cord), which causes severe muscle weakness, numbness, and sometimes paralysis of the arms and legs, and optic neuritis (inflammation of the optic nerve), which causes eye pain and vision loss. Transverse myelitis can additionally cause respiratory failure, sensory disturbances and loss of bladder and bowel control.2-4
Within five years of disease onset, 50% of relapsing NMO patients sustain permanent, severe disability, including paralysis and blindness.10 Most NMO-related deaths result from respiratory complications from NMO attacks10,11; in one report, 30% of patients died within 5 years of disease onset.10
The relapsing form of NMO primarily affects women.13 There are no approved treatments for the disease. Current management focuses primarily on using immunosuppression in an attempt to reduce the frequency and severity of attacks.
About Soliris
Soliris is a first-in-class terminal complement inhibitor developed from the laboratory through regulatory approval and commercialization by Alexion. Soliris is not approved for the treatment of patients with NMO in any country. Soliris is approved in the US,
Important Safety Information
The US product label for Soliris includes a boxed warning: "Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Comply with the most current
In patients with PNH, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, nasopharyngitis (runny nose), back pain and nausea. Soliris treatment of patients with PNH should not alter anticoagulant management because the effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. In patients with aHUS, the most frequently reported adverse events observed with Soliris treatment in clinical studies were hypertension, upper respiratory tract infection, diarrhea, headache, anemia, vomiting, nausea, urinary tract infection, and leukopenia. Please see full prescribing information for Soliris, including boxed WARNING regarding risk of serious meningococcal infection.
About Alexion
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Safe Harbor Statement
This news release contains forward-looking statements, including statements related to anticipated clinical development, regulatory and commercial milestones and potential health and medical benefits of Soliris® (eculizumab) for the potential treatment of patients with severe and relapsing neuromyelitis optica. Forward-looking statements are subject to factors that may cause Alexion's results and plans to differ from those expected, including for example, decisions of regulatory authorities regarding marketing approval or material limitations on the marketing of Soliris for its current or potential new indications, and a variety of other risks set forth from time to time in Alexion's filings with the
References
1 Pittock SJ, McKeon A, Mandrekar JN, Weinshenker BG, Lucchinetti CF, Wingerchuk DM. Pilot clinical trial of eculizumab in AQP4-Ig-G-positive NMO. Presented at the 2012 annual meeting of the
2 Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6(9):805-15.
3 Wingerchuk DM. Diagnosis and treatment of neuromyelitis optica. Neurologist. 2007;13(1):2-11.
4 Wingerchuk DM, Weinshenker BG. Neuromyelitis optica. Curr Treat Options Neurol. 2008;10(1):55-66.
5 Jarius S, Wildemann B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol. 2010;6:383-92.
6 Hinson SR, Romero MF, Popescu BFG, et al. Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Nat Acad Sci. 2012;109(4):1245-50.
7 Hinson SR, Pittock SJ, Lucchinetti CF, et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology. 2007;69:2221-31.
8 Tuzun E, Kurtuncu M, Turkoglu R, et al. Enhanced complement consumption in neuromyelitis optica and Behcet's disease patients. J Neuroimmunol. 2011;233(1-2):211-5.
9 Kuroda H, Fujihara K, Takano R, et al. Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica. J Neuroimmunol. 2012; pii: S0165-5728(12)00275-5.
10 Wingerchuk DM, Hogancamp WF,O'Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology 1999 Sep 22;53(5):1107-14.
11 Kitley J, Leite MI, Nakashima I, et al. Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the
12 Mata S, Lolli F. Neuromyelitis optica: an update. J Neurol Sci. 2011;303(1-2):13-21.
13 Wingerchuk DM. Neuromyelitis optica.
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