Branded glatiramer acetate (Copaxone) was approved by the FDA in 1995 at a dose of 20 mg per day, injected subcutaneously for the treatment of relapsing-remitting MS. It is a “immunomodulatory” medication, and it seems to stimulate protective immunity in MS. It was created to reduce The Costs of treating multiple sclerosis. It is manufactured by Teva Pharmaceuticals and may account for over 50% of that firm’s profits. In 2014, it had sales of almost 4 billion dollars and was in the top 10 of all drugs sold in the US. The patent for this medication expires this year.
The medication is difficult to manufacture. It is a complex and not a simple small-molecule drug. It was first studied in the 1960s, and it took Teva years to produce a commercial product.
The Food and Drug Administration recently approved a generic glatiramer acetate termed Glatopa, manufactured by Sandoz / Novartis. The FDA did not require that a clinical trial be performed to demonstrate equivalence but rather that the generic product met bioequivalence standards consistent with other injectable generic drugs. The agency concluded that the manufacturing method, the physicochemical properties, and the effects on the animal model termed experimental autoimmune encephalitis met these criteria.
By contrast, the European Medicines Agency (EMA) required a clinical trial before considering approval of another generic made by Synthon. This study was recently completed and reported, and the generic seemed as effective as the brand in the primary outcome measure, which was based on MRI findings.
So, Will Generic Copaxone Reduce The Costs Of Treating Multiple Sclerosis? The US product, Glatopa, is priced at $63,000 per year. This is $11,000 a year lower than the brand Copaxone 25 mg a day but is only $2,000 a year lower than the new brand of Copaxone 40 mg 3 times a week, which costs $65,000 per year. Most Copaxone 20 mg a day patients have switched to 40 mg 3 times a week. The generic thus does not replace that product. It takes several years for prices of a generic drug to fall. At some point, we will see generics for beta interferons. Likely, they will not have substantially lower prices than the branded drugs.
This combination seems too good to be true. Fifty-seven patients with episodic migraine, meaning 14 or less attacks per month, were given Zocor (simvastatin) 20 mg and vitamin D3 1000 units twice daily. The treatment group had a very high reduction of 8 migraine days per month compared to only 1 in the placebo group. Twenty-five percent of patients in the treatment group had a 50% reduction in headache days compared to only 1 patient (3%) in the placebo group. As expected, adverse effects were similar in both groups. This was a small study and needs to be replicated, but the treatment effect seems very high and placebo effect very low. This low placebo effect is unusual in migraine studies, as it is usually higher.
See Annals of Neurology, 2015, with lead author Buettner.
Saying “persons with MS” seems clumsy, but when MS patients are asked what they want to be called, they often choose phrases such as people with MS, persons with MS, or MSers.
Back to vitamin D. Many studies have shown that low vitamin D levels increase the risk of being diagnosed with MS and correlate with a higher number of new MRI lesions, relapses, and probably disability. Thus, raising vitamin D levels in the blood has been a target for years, but how much vitamin D to take?
In the United States, vitamin D levels are usually reported as nanograms per mL. Most laboratories establish a level of at least 30 to be acceptable. Many MS specialists believe that levels above 50 and perhaps above 75 are desirable. This, however, is not universally accepted, and there may be risks at higher levels.
There is a new study, analyzing blood that was stored from a large Betaseron study from 2003 to 2005 of over 1400 patients. It seems that increasing vitamin D levels from 20 to 40 reduced new MRI lesions by over 30%. Despite the effects on MRI, the higher levels did not seem to be correlated with brain atrophy or clinical outcomes.
It is possible that increasing the levels above the physiological limit of vitamin D, which is 60, is not beneficial and potentially harmful. A recent study utilized 14,000 units a day, and this showed no added benefit. For most patients, a dose of 2000 to 4000 units a day would probably achieve a level of at least 40. To me, levels between 40 and 60 seem optimal. Some patients may require 5000 units a day or higher. New studies may alter these recommendations.
For more information, see JAMA Neurology, December 2015, page 1458.
Progressive multifocal leukoencephalopathy (PML) is the most feared serious adverse effect of use of Tysabri for relapsing MS. The medication is given by infusion every 4 weeks, with that interval determined by studies showing that 80% of the receptors continued to be blocked at that point. At 12 weeks, the therapeutic effect is reduced to 50% and at 6 months almost to zero. When Tysabri is stopped, there may be clinical and MRI worsening (rebound), but this usually starts at 10 to 12 weeks.
Several reports indicate that women who weigh less than 160 pounds may safely be dosed every 6 weeks with no loss of efficacy of the medication. A new study did not limit patients by weight. About 1000 patients who received standard dose Tysabri were compared with about another 1000 who received extended interval dose therapy, usually 6 to 8 weeks and as long as 8-1/2 weeks. No patient in the extended dose arm had a relapse and none developed PML. On the other hand, the standard dosing group had 4 PML cases during the study.
This strategy may allow continued dosing of a very effective medication for relapsing MS.
This study was presented at the 2015 ECTRIMS Meeting. Lead author was Zhovtis Ryerson, MD.
They may, but only if combined with cognitive and physical training. This is the conclusion of a 3-year study from Toulouse, France, presented at the most recent Clinical Trials on Alzheimer’s Disease Conference. The lead author was Bruno Vellas, MD. Sixteen hundred and eighty people who reported subjective memory complaints were followed for 3 years. Cognitive training was to teach the use of adaptive strategies to solve everyday problems, such as using mnemonics to remember grocery lists. Physical training involved at least 150 minutes of moderate exercise each week, mainly walking 30 minutes a day. Further, there was an at-home exercise plan that was reviewed and updated. Nutritional counseling was also done. Subjects also took a twice-daily, specially compounded combination of 400 mg of DHA and 112.5 mg of EPA. These are the components of omega-3 supplements.
Subjects were randomized to 1 of 4 arms: omega-3 supplements alone, placebo capsules alone, cognitive and physical training without supplements, and both training and supplements.
Patients taking supplements alone or placebo were similar in the rate of decline from baseline. Those in the training program, with or without supplements, had a significant improvement in cognitive score during the first year, less so in the second year but remained above baseline. The best outcome occurred in the training program plus omega-3 supplement group. Their test scores remained completely stable during the entire 3-year period.
The results of the study seem intuitive. The program is easy to implement.
Some parents believe that vaccinating their children puts them at risk for numerous disorders, including autism. A new study adds weight to the considerable amount of evidence that says otherwise. In adults, vaccination against influenza has been shown to reduce risk of stroke, heart attack, and all-cause mortality. Stroke in children was analyzed as well. Infection was reported within a week of stroke in 18% of patients compared to 3% of controls. Children with stroke were less likely to have received all or most of the recommended vaccinations. The idea that vasoactive medications present in common cold medicines was the cause was not supported.
Infection seems to act as a trigger for childhood stroke, while routine vaccinations appeared protective. A preceding infection in fact increases the risk sixfold.