Copaxone® (Glatiramer Acetate) Multiple Sclerosis (MS) Injectable Disease Modifying Therapy

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Copaxone® (Glatiramer Acetate)

Overview:

Copaxone® (glatiramer acetate) is a synthetic protein that simulates myelin basic protein, a component of the myelin that insulates nerve fibers in the brain and spinal cord. This drug seems to block myelin-damaging T-cells through a mechanism that is not completely understood.

Glatiramer acetate is approved by the U.S. Food and Drug Administration (FDA) to reduce the frequency of relapses in patients with relapsing-remitting MS. It is also approved for use in individuals who have experienced a first clinical episode (clinically-isolated syndrome) and have MRI features that are consistent with multiple sclerosis.

The mechanism(s) by which glatiramer acetate exerts its effects in patients with MS is (are) not fully elucidated. However, it is thought to act by modifying immune processes that are currently believed to be responsible for the pathogenesis of MS. This hypothesis is supported by findings of studies that have been carried out to explore the pathogenesis of experimental allergic encephalomyelitis (EAE), a condition induced in several animal species through immunisation against central nervous system derived material containing myelin and often used as an experimental animal model of MS. Studies in animals and in MS patients suggest that upon its administration, glatiramer acetate-specific suppressor T cells are induced and activated in the periphery.

In January, 2014, the FDA approved a new 40 mg/mL dose of this medication, injected three times per week, which is double the standard 20 mg/mL dose that is injected daily. The approval was based on benefits and safety demonstrated in a one-year phase III trial comparing the higher, less-frequent dose of the medication with placebo. The standard dosing option continues to be available.

Dosing:

Copaxone comes in a prefilled syringe and is given by subcutaneous (under the skin) injection once a day. The recommended daily dose of Copaxone is 20 mg. To keep track of your schedule for taking Copaxone, you should plan your injection at the same time every day. You’ll get your first injection of Copaxone in your doctor’s office. Your doctor will give you complete instructions about how to take Copaxone and will help you or a friend or family member learn to give the injection, so that you can take Copaxone on your own at home. The instructions for taking Copaxone illustrate 7 different areas on your body where the medicine can be injected. To reduce injection site reactions (swelling, redness, pain, or discoloration), choose a different place for the injection every day of the week.

In January, 2014, the FDA approved a new 40 mg/mL dose of this medication, injected three times per week, which is double the standard 20 mg/mL dose that is injected daily. The approval was based on benefits and safety demonstrated in a one-year phase III trial comparing the higher, less-frequent dose of the medication with placebo. The standard dosing option continues to be available.

Copaxone pre-filled syringes should be refrigerated. If this is not possible, the syringes can be stored at room temperature (not above 77ºF) for 1 month. Copaxone must be stored in a place away from the light and should never be frozen.

Efficacy Results:

A total of 269 patients have been treated with Copaxone in three controlled trials. The first was a two-year study involving 50 patients (Copaxone n=25, placebo n=25) who were diagnosed with relapsing-remitting MS by the then-applicable standard criteria, and who had at least two attacks of neurological dysfunction (exacerbations) during the preceding two years. The second study applied the same inclusion criteria and included 251 patients treated for up to 35 months (Copaxone n=125, placebo n=126). The third study was a nine-month study involving 239 patients (Copaxone n=119, placebo n=120) where inclusion criteria were similar to those in the first and second studies with the additional criterion that patients had to have at least one gadolinium-enhancing lesion on the screening MRI.

In clinical trials in MS patients receiving Copaxone, a significant reduction in the number of relapses, compared with placebo, was seen.

In the largest controlled study, the relapse rate was reduced by 32% from 1.98 under placebo to 1.34 under glatiramer acetate.

Exposure data are available for up to twelve years in 103 patients treated with Copaxone.

Copaxone has also demonstrated beneficial effects over placebo on MRI parameters relevant to relapsing-remitting MS.

Copaxone had, however, no beneficial effect on progression of disability in relapsing-remitting MS patients.

There is no evidence that Copaxone treatment has an effect on relapse duration or severity.

There is currently no evidence for the use of Copaxone in patients with primary or secondary progressive disease.

New Study:

A new study on Copaxone in 2013 called GALA 2013 took place. The study was a 12-month, double-blind, placebo-controlled, multinational study. Patients with RRMS were randomized to receive 3-times-a-week COPAXONE® 40 mg/mL (n=943) or placebo (n=461). The primary endpoint was total number of confirmed relapses.

COPAXONE® 40 mg/mL significantly reduced the total number of relapses by 34% compared with placebo.

A 45% reduction in the mean number of enhancing lesions on T1-weighted images with 3-times-a-week COPAXONE® 40 mg/mL compared with placebo.

Three times a week COPAXONE® 40 mg/mL demonstrated a 35% reduction in the cumulative number of new or enlarging T2 lesions compared with placebo at 6 and 12 month.

Side Effects:

COPAXONE® is contraindicated in patients with known hypersensitivity to glatiramer acetate or mannitol.

Approximately 16% of patients exposed to COPAXONE® 20 mg per mL compared to 4% of those on placebo, and approximately 2% of patients exposed to COPAXONE® 40 mg per mL compared to none on placebo experienced a constellation of symptoms immediately after injection that included at least 2 of the following: flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and urticaria. In general, these symptoms have their onset several months after the initiation of treatment, although they may occur earlier, and a given patient may experience 1 or several episodes of these symptoms. Typically, the symptoms were transient and self-limited and did not require treatment; however, there have been reports of patients with similar symptoms who received emergency medical care.

Transient chest pain was noted in 13% of COPAXONE® 20 mg per mL patients compared to 6% of placebo patients, and approximately 2% of COPAXONE® 40 mg per mL patients compared to 1% on placebo. While some episodes of chest pain occurred in the context of the immediate postinjection reaction described above, many did not. The temporal relationship of this chest pain to an injection was not always known. The pain was usually transient, often unassociated with other symptoms, and appeared to have no clinical sequelae. Some patients experienced more than 1 such episode, and episodes usually began at least 1 month after the initiation of treatment.

At injection sites, localized lipoatrophy and, rarely, injection site skin necrosis may occur. Lipoatrophy may occur at various times after treatment onset (sometimes after several months) and is thought to be permanent. There is no known therapy for lipoatrophy.

Because COPAXONE® can modify immune response, it may interfere with immune functions. For example, treatment with COPAXONE® may interfere with recognition of foreign antigens in a way that would undermine the body’s tumor surveillance and its defenses against infection. There is no evidence that COPAXONE® does this, but there has not been a systematic evaluation of this risk.

In controlled studies of COPAXONE® 20 mg per mL, the most common adverse reactions with COPAXONE® vs placebo were injection site reactions (ISRs), such as erythema (43% vs 10%); vasodilatation (20% vs 5%); rash (19% vs 11%); dyspnea (14% vs 4%); and chest pain (13% vs 6%).

In a controlled study of COPAXONE® 40 mg per mL, the most common adverse reactions with COPAXONE® vs placebo were ISRs, such as erythema (22% vs 2%).

SRs were one of the most common adverse reactions leading to discontinuation of COPAXONE®. ISRs, such as erythema, pain, pruritus, mass, edema, hypersensitivity, fibrosis, and atrophy, occurred at a higher rate with COPAXONE® than placebo.


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