How Well Do You Know COPAXONE® (glatiramer acetate injection)?

This year, Teva is celebrating the 25th anniversary of the FDA approval of COPAXONE® (glatiramer acetate injection), but the story goes back much further. Hear what some of Teva's most prominent R&D leaders have to say about the history and origins of the treatment.

Sponsored by Teva Pharmaceuticals

Teva has been committed to patients living with multiple sclerosis (MS) since COPAXONE® gained FDA (Food and Drug Administration) approval 25 years ago—but the story dates back much further and is a lot deeper than people may think.

About COPAXONE

COPAXONE is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. COPAXONE is contraindicated in patients with known hypersensitivity to glatiramer acetate or mannitol. For additional important safety information, please see below.

To celebrate this anniversary milestone and learn some lesser-known facts, a trivia session was organized with some of Teva’s most prominent R&D (Research & Development) leaders. In this test of knowledge on the history of multiple sclerosis (MS) and the origins of COPAXONE, fascinating details and insights into how data are impacting future outcomes for patients emerged.

Meet Our Players

Jessica Alexander, PhD, Global Medical Director, Neurology; Sivan Weiss, MSc, Senior Director, Statistical Therapeutic Area Head of Neurology, Psychiatry and Biosimilars; Levana Volovsky, MSc, Director, Global Regulatory; and Michaela Vardi, PhD, Director, Teva Specialty Pharmaceuticals.

To kick off the discussion, we revisited the origins of MS. The team did not hesitate before answering correctly, eager to add color to the beginnings of treating the complex disease that affects the central nervous system (CNS). How will you do? Try your knowledge below:

When was multiple sclerosis first recognized as a disease?


Who was “the father of neurology” who first noticed characteristic scars of multiple sclerosis?


MS is an autoimmune disorder1 characterized by immune-mediated demyelination, inflammation, and progressive neurodegeneration in the CNS.2 It was first recognized as a disease in 1868 by Jean-Martin Charcot, whose detailed description of MS, accompanied by drawings of lesions expanding from the ventricles into the cerebral hemispheres, provided the earliest insight into the pathology of MS involving both the brain and spinal cord.3,4

Talking about one pioneer naturally led to another prominent mind in the field. Ruth Arnon, an immunology professor at the Weizmann Institute of Science, is one of the scientists behind the development of COPAXONE, along with Michael Sela and Devorah Teitelbaum.5 “COPAXONE started in the lab in 1967,” Vardi said.

“The term ‘serendipitous’ has oft and appropriately been used to describe the development,” said Dr. Alexander, who revealed the lesser-known story of the true origins of COPAXONE.6 “In the 1960s, Arnon and Sela were seeking a synthetic encephalitogenic peptide resembling what we now know as myelin basic protein (MBP) to induce experimental autoimmune encephalomyelitis (EAE), the non-human animal model of MS. COPAXONE (then referred to as Copolymer 1, now formally known as Cop-1) was developed to cause the animal model of MS, and ensuing experiments revealed that it reduced the disease in the model.6 What followed was decades of further preclinical and clinical research by teams at Weizmann, Teva, and globally, by scientists and clinicians dedicated to the advancement of care of MS patients.”

“Teva purchased the license from the Weizmann Institute in 1987,” Vardi added. “At the time COPAXONE was developed and got approved in 1996, the field of treatment for MS was completely different than what it is today. 25 years ago, COPAXONE became the first in a new class of treatment.”

“Since then, we’ve collected a large database of clinical and real-world patient data,” noted Weiss.

The active pharmaceutical ingredient (API) in COPAXONE is glatiramer acetate (GA), which is a highly complex, synthetic mixture of polypeptides composed of four amino acids.1,7 Clinically, COPAXONE reduces the frequency of relapses in patients with relapsing forms of MS.8

Immediate Post-Injection Reaction: 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 that may occur immediately (within seconds to minutes, with the majority of symptoms observed within 1 hour) after injection and included at least 2 of the following: flushing, chest pain, palpitations, tachycardia, 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.

Ready to learn more? See how you do with the following trivia:

Relapsing-remitting multiple sclerosis is characterized by clearly defined attacks of new or increasing neurologic symptoms, followed by periods of partial or complete recovery.

How many people living with MS are affected by RMS?9


Globally, how many people are affected by multiple sclerosis?10


Men are 2 to 3 times more likely to have MS than women.11


With 23 FDA-approved therapies for RMS, representing diverse mechanisms of action,12 “the challenge ahead is to understand how to best apply the treatments to individual patients over the course of MS. This refers to treatment considerations at diagnosis, or even relative to RIS (Radiologically Isolated Syndrome), according to prognosis and through key milestones such as family planning,” noted Dr. Alexander.

According to the National Multiple Sclerosis Society, four times as many women have MS as men, and 2.8 million people are diagnosed. Women living with MS comprise 74% of all MS diagnoses.10,11 Teva continues its commitment to women’s health through real-world evaluation of COPAXONE safety during pregnancy and breastfeeding.

Volovsky added, “COPAXONE was also evaluated in a specific placebo-controlled study with clinically isolated syndrome (CIS) patients for three years, and subsequently in open-label for two more years.” Click here to see the studies.

“There is more and more interest in understanding the optimal approach to treat individual patients as early as possible,” Dr. Alexander said.

COPAXONE may have diverse effects on both the innate and adaptive immune systems. Several potential mechanisms of GA are supported by research data.2 GA may act on the immune system in an antigen-dependent1 or antigen-independent manner.2 The active moieties, including antigen epitopes of GA, that confer these immunomodulatory effects are unknown.7

The mechanism(s) by which glatiramer acetate exerts its effects in patients with MS are not fully understood. However, glatiramer acetate is thought to act by modifying innate and adaptive immune processes that are believed to be responsible for the pathophysiology of MS. This hypothesis is supported by studies in individuals with MS as well as in experimental autoimmune encephalomyelitis (EAE), a condition induced in non-human animals through immunization against central nervous system-derived material containing myelin and often used as an experimental animal model of MS. Studies suggest that upon its administration, glatiramer acetate-specific suppressor T-cells are induced and activated in the periphery. Because glatiramer acetate can modify immune functions, concerns exist about its potential to alter naturally-occurring immune responses. There is no evidence that glatiramer acetate does this, but this has not been systematically evaluated. Because COPAXONE can modify immune response, it may interfere with immune functions. For example, treatment with COPAXONE may interfere with the recognition of foreign antigens in a way that would undermine the body’s tumor surveillance and its defenses against infection.8

In the largest pivotal trial ever conducted for COPAXONE, taking COPAXONE 40 mg/mL 3-times-a-week significantly reduced the number of relapses at 1 year compared with placebo (an inactive substance).8,13

Chest Pain: 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 Post-Injection 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.

Please see additional important safety information at: www.copaxonehcp.com and full prescribing information here.

As part of the 25-year heritage of COPAXONE, Teva is celebrating the MS community with a new social campaign, #MySilverLining, which strives to amplify patient and Care Partner stories and experiences.

“COPAXONE still has a future,” Weiss punctuated. More than 50 years after its discovery and 25 years since FDA-approval, Teva is building from the legacy of COPAXONE to unlock new treatment possibilities for people living with MS. This includes increasing access for additional patient populations and expanding into international markets. More data and research for relapsing forms of MS mean an increase in understanding of how to better manage therapy for patients.

When writing prescriptions for COPAXONE, health care professionals should note “Dispense as written” to help ensure consistency for their patients.

To discover more, visit www.copaxonehcp.com, or see what is being shared with #MySilverLining.

Indication

COPAXONE® is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Important Safety Information

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

Immediate Post-Injection Reaction: 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 that may occur immediately (within seconds to minutes, with the majority of symptoms observed within 1 hour) after injection and included at least 2 of the following: flushing, chest pain, palpitations, tachycardia, 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.

Chest Pain: 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 Post-Injection 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.

Lipoatrophy and Skin Necrosis: 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.

Potential Effects on Immune Response: 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.

Hepatic Injury: Cases of hepatic injury, some severe, including liver failure and hepatitis with jaundice, have been reported with COPAXONE®. Hepatic injury has occurred from days to years after initiating treatment with COPAXONE®. If signs or symptoms of liver dysfunction occur, consider discontinuation of COPAXONE®.

Common Adverse Reactions: 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%).

ISRs 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.

Please see full Prescribing Information for COPAXONE®.

Injections for 3-times-a-week COPAXONE® 40 mg must be at least 48 hours apart.

REFERENCES
1. Crommelin DJA, et al. Non-Biological Complex Drugs. Cham: Springer International Publishing; 2015.
2. Prod'homme T, et al. Cold Spring Harb Perspect Med. 2018;9(2):a029249.
3. Pearce JMS. Historical descriptions of multiple sclerosis. Eur Neurol. 2005;54:49–53.
4. Orrell RW. Multiple Sclerosis: The history of a disease. [Book Review]. J R Soc Med. 2005;98:289.
5. Steinman L, Shoenfeld Y. From defining antigens to new therapies in multiple sclerosis: honoring the contributions of Ruth Arnon and Michael Sela. J Autoimmun. 2014 Nov;54:1-7. doi: 10.1016/j.jaut.2014.08.001. Epub 2014 Oct 11. PMID: 25308417.6. Johnson KP. The remarkable story of COPAXONE®. New York, NY: Diamedica Publishing, 2010.
7. Varkony H, et al. Expert Opin Pharmacother. 2009;10(4):657-668.
8. COPAXONE® (glatiramer acetate injection) Current Prescribing Information Parsippany, NJ. Teva Neuroscience, Inc.
9. Relapsing-remitting MS (RMS). National Multiple Sclerosis Society website. Accessed May 25, 2021. https://www.nationalmssociety.org//What-is-MS/Types-of-MS/Relapsing-remitting-MS.
10. Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, Robertson N, La Rocca N, Uitdehaag B, van der Mei I, Wallin M, Helme A, Angood Napier C, Rijke N, Baneke P. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler. 2020 Dec;26(14):1816-1821. doi: 10.1177/1352458520970841. Epub 2020 Nov 11. PMID: 33174475; PMCID: PMC7720355.
11. Who gets MS? (Epidemiology). National Multiple Sclerosis Society website. Accessed May 25, 2021. https://www.nationalmssociety.org/What-is-MS/Who-Gets-MS
12. Treating MS. Medications. National Multiple Sclerosis Society website. Accessed June 8, 2021. https://www.nationalmssociety.org/Treating-MS/Medications.
13. Khan O, Rieckmann P, Boyko A, Selmaj K, Zivadinov R; for the GALA Study Group. Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis. Ann Neurol. 2013;73(6):705-713. doi:10.1002/ana.23938

COP-46600
July 2021