scholarly journals Comparative Long-Term Preclinical Safety Evaluation of Two Glatiramoid Compounds (Glatiramer Acetate, Copaxone®, and TV-5010, Protiramer) in Rats and Monkeys

2011 ◽  
Vol 40 (1) ◽  
pp. 40-54 ◽  
Author(s):  
Yuval Ramot ◽  
Moti Rosenstock ◽  
Ety Klinger ◽  
Dizza Bursztyn ◽  
Abraham Nyska ◽  
...  
Keyword(s):  
Glatiramer Acetate ◽  
Complex Mixture ◽  
Safety Evaluation ◽  
Sprague Dawley ◽  
Subcutaneous Injections ◽  
Toxicity Studies ◽  
Sprague Dawley Rats ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Glatiramer acetate (GA), the active ingredient in Copaxone®, is a complex mixture of polypeptides used for the treatment of relapsing remitting multiple sclerosis. Glatiramoids are related mixtures that may differ in some characteristics of the prototype molecule. Our aim is to describe the long-term toxicity studies with protiramer (TV-5010), a new glatiramoid, in comparison with similar studies conducted with GA. The toxicity of twice-weekly subcutaneous injections of protiramer to Sprague-Dawley rats (twenty-six weeks) and cynomolgus monkeys (fifty-two weeks) was compared with similar studies done with daily subcutaneous injections of GA. Daily treatment with GA was safe and well tolerated, without systemic effects or death. Protiramer administration was not as well tolerated as GA and led to dose- and time-related mortalities, probably mediated through severe injection-site lesions both in rats and in monkeys. Bridging fibrosis in the liver and severe progressive nephropathy were seen in rats. A dose-related increase in eosinophils was observed in monkeys. The protiramer toxicity studies show that minor variations in the manufacturing of glatiramoids may lead to significant toxic effects. It is therefore essential that the safety of any new glatiramoid be studied in long-term preclinical studies before exposing humans.

Long-term (up to 22 years), open-label, compassionate-use study of glatiramer acetate in relapsing—remitting multiple sclerosis

2008 ◽  
Vol 14 (4) ◽  
pp. 494-499 ◽  
Author(s):  
Aaron Miller ◽  
Vincent Spada ◽  
Dorothy Beerkircher ◽  
Rivka Riven Kreitman
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Glatiramer Acetate ◽  
Open Label ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Pretreatment Score

To evaluate the safety and efficacy of long-term glatiramer acetate (GA) therapy, 46 patients with relapsing—remitting multiple sclerosis (RRMS) were treated for up to 22 years in an ongoing, open-label study. Kurtzke expanded disability status scale (EDSS) was measured every six months, relapses were reported at occurrence and patients self-reported adverse events (AEs). At GA initiation, disease durations ranged from 0—20 years (median 6.0 years) and at data cut-off (October 2004), GA therapy duration ranged from 1—22 years (median 12.0 years). Mean EDSS score increased 0.9 ± 1.9 from the pretreatment score (3.0 ± 1.8; P = 0.076). Only 10/28 (36%) patients with baseline EDSS <4.0 had a last observed value ≥ 4.0 and 8/34 (24%) with entry EDSS < 6.0 reached EDSS ≥ 6.0. A majority (57%) maintained improved or unchanged EDSS scores. Annualized relapse rate decreased to 0.1 ± 0.2 from 2.9 ± 1.4 prestudy ( P < 0.0001). Of the 18 remaining patients in October 2004 (average disease duration 23 years), 17% with baseline EDSS scores < 4.0 reached EDSS ≥ 4.0 and 28% with baseline scores < 6.0 reached EDSS ≥ 6.0. Adverse events were similar to those reported in short-term clinical trials. This study shows a low rate of relapses and EDSS progression in RRMS patients on GA for up to 22 years. Multiple Sclerosis 2008; 14: 494—499. http://msj.sagepub.com

The incidence of chronic progressive nephrosis in young Sprague-Dawley rats from two different breeders

1998 ◽  
Vol 32 (4) ◽  
pp. 477-482 ◽  
Author(s):  
Maud Palm
Keyword(s):  
Kidney Function ◽  
Young Female ◽  
Female Rats ◽  
Common Finding ◽  
Sprague Dawley ◽  
Laboratory Rats ◽  
Toxicity Studies ◽  
Sprague Dawley Rats ◽  
Males And Females

Chronic progressive nephrosis (CPN) in rats may not only become a problem in long-term toxicity studies but also in short-term studies, if the breeding stock is not carefully selected with respect to the kidney function. This paper presents differences in kidney function between young rats of the same strain, Sprague-Dawley, but from two different breeders ('set A' and 'set B' rats). In set A rats, protein in the urine was present in the males, which is a common finding. In set B rats, not only the males but also the females excreted protein in the urine. The method used to detect protein in the urine does not normally show a positive protein result in the young female rats. At the age of 3 months signs of chronic progressive nephrosis were observed in 55% of the males and in 15% of the females in set B. Two months later, the incidence had increased to about 70–80% in males and 50% in females. At 8 months, the incidence was similar, but the severity had increased. These values were compared with those obtained from the set A rats, none of which showed any signs of the disease at the age of 5 months and only 5% of the males and females at the age of 8 months. The results indicated that an increased excretion of protein in the urine may be used as an indicator for chronic progressive nephrosis in the rat and that not only the strain but also the source is important in selecting laboratory rats for toxicity studies.

scholarly journals Clinical Utility of Glatiramer Acetate in the Management of Relapse Frequency in Multiple Sclerosis

2012 ◽  
Vol 4 ◽  
pp. JCNSD.S8755 ◽  
Author(s):  
Oscar Fernández
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Clinically Isolated Syndrome ◽  
Common Disease ◽  
Definite Multiple Sclerosis ◽  
Relapsing Remitting ◽  
Clinical Episode ◽  
Clinically Definite Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Glatiramer acetate (GA) represents one of the most common disease-modifying therapies for multiple sclerosis. GA is currently approved for patients at high risk of developing clinically definite multiple sclerosis (CDMS) after having experienced a well-defined first clinical episode (clinically isolated syndrome or CIS) and for patients with relapsing-remitting multiple sclerosis (RRMS). GA's efficacy and effectiveness to reduce relapse frequency have been proved in placebo-controlled and observational studies. Comparative trials have also confirmed the lack of significant differences over other choices of treatment in the management of relapse frequency, and long-term studies have supported its effect at extended periods of time. Additionally, RRMS patients with suboptimal response to interferon β may benefit from reduced relapse rate after switching to GA, and those with clinically isolated syndrome may benefit from delayed conversion to CDMS. All these results, together with its proven long-term safety and positive effect on patients’ daily living, support the favorable risk-benefit of GA for multiple sclerosis treatment.

Benefit of Endermology on Indurations and Panniculitis/Lipoatrophy During Relapsing–Remitting Multiple Sclerosis Long-Term Treatment with Glatiramer Acetate

2014 ◽  
Vol 31 (8) ◽  
pp. 904-914 ◽  
Author(s):  
Carmen Márquez-Rebollo ◽  
Luisa Vergara-Carrasco ◽  
Rosa Díaz-Navarro ◽  
Delia Rubio-Fernández ◽  
Pablo Francoli-Martínez ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Contact dermatitis induced by glatiramer acetate

2011 ◽  
Vol 17 (11) ◽  
pp. 1390-1392 ◽  
Author(s):  
S Haltmeier ◽  
M Yildiz ◽  
S Müller ◽  
MD Anliker ◽  
L Heinzerling
Keyword(s):  
Contact Dermatitis ◽  
Glatiramer Acetate ◽  
Lymphocyte Transformation ◽  
Lymphocyte Transformation Test ◽  
Topical Steroids ◽  
Scratch Testing ◽  
Subcutaneous Injections ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Safe Treatment Option

Glatiramer acetate (Copaxone®) is an immunomodulatory polypeptide used in patients with relapsing–remitting multiple sclerosis. It represents a safe treatment option with mild side effects. In this study, we look at a 39-year-old woman who received glatiramer acetate as subcutaneous injections for two months and developed contact dermatitis. The drug had to be stopped, and treatment with topical prednisone was initiated. Prick/scratch testing was negative but the lymphocyte transformation test was highly positive for glatiramer acetate. This is the first report on contact dermatitis induced by glatiramer acetate injections. The treatment consisted of local topical steroids and cessation of the drug.

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