Generic Glatiramer Acetate Research Articles

Tolerability and Acceptance of Switching from Brand to Generic Glatiramer Acetate in Multiple Sclerosis.

Background: The costs of disease-modifying therapies (DMTs) for multiple sclerosis (MS) have increased interest in generic alternatives. Methods: This prospective and observational study aims to investigate the safety, tolerability, and acceptance of switching from brand glatiramer acetate (GA) 40 mg/mL three times per week (Copaxone®) to generic GA 40 mg/mL three times per week (Glatiramyl®). Conducted at the Neurocenter of Southern Switzerland from September 2020 to September 2021, the study enrolled 27 patients; 21 completed the study. Participants reported on local and systemic side effects three months before and after the switch, and on switch acceptance by means of visual analogue scales (from 0 to 10). Results: Results indicated that those on generic GA experienced fewer local (81.0% vs. 96.3%) and systemic (33.3% vs. 59.3%) adverse events than with the brand drug. The median intensity of local adverse events was 8 (4-20) on generic GA vs. 16 (9-22) on brand GA, while the median intensity of systemic adverse events was similar between generic and brand GA [0 (0-27) vs. 0 (0-21.5), respectively]. Seventy-one percent of participants rated their acceptance of generic GA as 7/10 or higher. Conclusions: The results suggest that switching from brand to generic GA 40 mg/mL is safe, well-tolerated, and accepted by patients with MS.

Demonstration of Equivalence of Generic Glatiramer Acetate and Copaxone®.

The objective of the current work was to demonstrate the equivalence of Mylan’s glatiramer acetate (GA) to that of the reference product Copaxone® (COP) using the four criteria for active pharmaceutical ingredient sameness as established by the US Food and Drug Administration (FDA). The reaction scheme used to produce Mylan’s glatiramer acetate (MGA) was compared with that of COP, determined from publicly available literature. Comparative analyses of MGA and COP were performed for physicochemical properties such as amino acid composition and molecular weight distributions. Spectroscopic fingerprints were obtained using circular dichroism spectroscopy. Structural signatures for polymerization and depolymerization including total diethylamine (DEA) content, relative proportions of DEA-adducted amino acids, and N-and C-terminal amino acid sequences were probed with an array of highly sensitive analytical methods. Biological activity of the products was assessed using validated murine Experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis. MGA is produced using the same fundamental reaction scheme as COP and was shown to have equivalent physicochemical properties and composition. Analyses of multiple structural signatures demonstrated equivalence of MGA and COP with regard to polymerization, depolymerization, and propagational shift. Examination of the impact on prevention and treatment of EAE demonstrated equivalence of MGA and COP with respect to both activity and toxicity, and thereby provided confirmatory evidence of sameness. A rigorous, multi-pronged comparison of MGA and COP produced using an equivalent fundamental reaction scheme demonstrated equivalent physicochemical properties, structural signatures for polymerization and depolymerization, and biological activity as evidenced by comparable effects in EAE. These studies demonstrate the equivalence of MGA and COP, establishing active ingredient sameness by the US Food and Drug Administration (FDA) criteria for GA, and provide compelling evidence that the FDA-approved generic MGA can be substituted for COP for the treatment of patients with relapsing-remitting MS.

Treatment patterns following initiation of generic glatiramer acetate among patients with multiple sclerosis from two large real-world databases in the United States

Introduction To better understand treatment patterns in US patients with multiple sclerosis (MS) initiating generic glatiramer acetate (GA), this study examined adherence, discontinuation and switching patterns from generic follow-on glatiramer acetate (FOGA) therapy in real-world patient cohorts. Methods Retrospective analyses utilized data from two large US databases (administrative claims and linked electronic medical records). Eligible adult MS patients had ≥1 pharmacy claim for FOGA during the identification period; the first FOGA claim was the index date. All analyses were descriptive; proportion of days covered (PDC) was calculated as a measure of adherence to FOGA during the follow-up period. Results The first cohort consisted of 95 patients, with 93.6% having a branded GA claim for Copaxone during the baseline period. Half these patients (48.4%) had high adherence to FOGA therapy (PDC: 0.8–1.0). Fifty-five patients (57.9%) initially discontinued FOGA with a mean persistence of 112 days. Of those who discontinued, 7.3% had no subsequent disease-modifying therapy (DMT), 30.9% restarted FOGA and 61.8% did not restart FOGA. The second cohort consisted of 1957 patients, with 63.8% having a branded GA claim for Copaxone during the baseline period and 33.5% were treatment naïve. The majority of patients (61.9%) had high adherence to FOGA therapy. A total of 1597 patients (81.6%) initially discontinued FOGA with a mean persistence of 93 days. Of those who discontinued, 55.8% switched to another DMT, 16.7% restarted FOGA and 37.5% had no subsequent DMT. Conclusion Adherence to FOGA therapy was reasonably high across cohorts; however, most patients discontinued their initial FOGA within four months of the index date and most switches from FOGA were to branded GA products.

Closing the Part D Coverage Gap and Out-of-Pocket Costs for Multiple Sclerosis Drugs.

To determine whether closing the Part D coverage gap (donut hole) between 2010 and 2019 lowered patients' out-of-pocket costs for disease-modifying therapies (DMTs) for multiple sclerosis (MS). Using nationwide Medicare Formulary and Drug Pricing Files, we analyzed Part D drug benefit design and DMT prices in 2010, 2016, and 2019. We calculated average monthly list prices for DMTs available in each year (4 DMTs in 2010, 11 DMTs in 2016, and 14 DMTs in 2019). We projected patients' annual out-of-pocket cost for each DMT alone under a standard Part D plan in that year. We estimated potential savings attributable to closing the coverage gap between 2010 and 2019 (beneficiaries' cost sharing dropped from 100% to 25%) under 3 scenarios: no increase in price, an inflation-indexed price increase (3% annually), and the observed price increase. Median monthly DMT prices rose from $2,804 to $5,987 to $7,009 over the years 2010, 2016, and 2019, respectively. Median projected annual out-of-pocket costs rose from $5,916 to $6,229 to $6,618. With unchanged or inflation-indexed DMT price changes, closing the coverage gap would have reduced annual out-of-pocket costs by $2,260 (38% reduction) and $1,744 (29% reduction), respectively. Despite having the lowest monthly price, generic glatiramer acetate had among the highest out-of-pocket costs ($6,731 to $6,939 a year) in 2019. Medicare Part D beneficiaries can pay thousands of dollars yearly out of pocket for DMTs. Closing the Part D coverage gap did not reduce out-of-pocket costs for patients because of simultaneous increases in DMT prices.

Multiple sclerosis relapse rates and healthcare costs of two versions of glatiramer acetate

Objective: To compare relapse rates and healthcare costs in MS patients treated with Glatopa 20 mg (generic glatiramer acetate) versus Copaxone 20 mg in a US managed care population.Methods: A retrospective claims study was conducted using the HealthCore Integrated Research Database. Patients with ≥1 Glatopa or Copaxone claim between 01 April 2015 (Glatopa) or 01 January 2013 (Copaxone) and 30 April 2018 were included. Patients with prior Copaxone 40 mg use or <1 year continuous health plan enrollment were excluded. Patients who switched from Glatopa to Copaxone were censored. Glatopa users were matched to Copaxone users, and outcomes measured at 6–12 months follow-up.Results: A total of 357 Glatopa and 2291 Copaxone patients qualified for inclusion; 158 per cohort were retained after matching. Baseline characteristics were well-balanced (mean age 49.9 years, 75% female, mean 3.8 Copaxone fills). At baseline, 8% of patients had ≥1 relapse with mean annualized relapse rates (ARR) of 0.18; at follow-up, the relapse rates were 8% versus 15% (Glatopa versus Copaxone; p = .05), and ARRs were 0.12 versus 0.30 (p = .05). 45% of Glatopa patients switched (back) to Copaxone 20/40 mg and were censored at that point. Mean (SD) all-cause medical and pharmacy costs were $51,507 ($28,494) versus $55,085 ($37,061; p = .50). Mean MS-related costs were $45,379 ($24,732) versus $47,949 ($32,615; p = .67), of which mean disease modifying therapy costs were $42,926 ($23,196) versus $44,932 ($28,554; p = .59). Results were similar in sensitivity analyses.Conclusions: In this real-world study, MS patients treated with Glatopa experienced similar health outcomes and costs compared to those treated with Copaxone, with a trend towards lower relapse rates (borderline statistically significant) and cost savings (not statistically significant).

Effect of generic glatiramer acetate on spending and use of drugs for multiple sclerosis.

To estimate changes in costs and utilization trends for disease-modifying therapies (DMTs) from 2011 to 2017 in the US Medicaid program. Using quarterly Medicaid State Drug Utilization Data from 2011 to 2017, we summarize trends in spending, utilization, and costs per prescription for 15 multiple sclerosis (MS) DMTs including brand and generic versions of glatiramer acetate. We use interrupted time series regression to estimate the effect of market entry of generic glatiramer acetate on cost per prescription of other self-administered DMTs. Gross annual expenditures on MS DMTs increased from $453 million to $1.32 billion between 2011 and 2017 within the Medicaid program. Increased spending was primarily driven by increases in per prescription costs, which doubled during the study period. Although total utilization was stable, product specific utilization shifted from injectable to oral DMTs. However, throughout the study, the plurality of utilization was glatiramer acetate. The introduction of generic glatiramer acetate in Q2 of 2015 was associated with an immediate increase of $441 (95% confidence interval [CI] $184-$697; p < 0.001) in the cost per prescription of branded glatiramer acetate followed by a gradual $52 per prescription reduction (95% CI -$86 to -$18) over time. There were minimal changes in the costs for the other DMTs. Spending on MS DMTs in the Medicaid program have more than doubled over the last 7 years primarily as a function of higher costs per prescription. Introduction of a generic glatiramer acetate product in 2015 had nominal effects on overall price trajectories and utilization within the class.

CO4 ALEMTUZUMAB VERSUS GENERIC GLATIRAMER ACETATE 20 MG IN PATIENTS WITH RELAPSING FORMS OF MULTIPLE SCLEROSIS: A COST-EFFECTIVENESS STUDY IN THE UNITED STATES

To evaluate the cost-effectiveness of alemtuzumab versus generic glatiramer acetate (GA) 20 mg in patients with relapsing multiple sclerosis (RMS) in the United States (US). A Markov model was developed from a US payer perspective with an annual cycle length and a time-horizon of 20 years. The modeled population represented pooled alemtuzumab-treated patients from the CARE-MS I (NCT00530348) and II (NCT00548405) trials. The British Columbia Multiple Sclerosis cohort data was used in the model to project the natural history of RMS disease progression. Treatment efficacy estimates for both therapies were derived from published network meta-analyses. Deterministic and probabilistic sensitivity analyses were conducted to assess any uncertainty in the model. The base-case analysis results showed that over a 20-year time-horizon, alemtuzumab was less costly compared with generic GA 20 mg ($421,996 vs $895,661). Alemtuzumab-treated patients accumulated a higher number of quality-adjusted life-years (QALYs) compared with those on generic GA 20 mg (8.977 vs 7.845). In addition, patients on alemtuzumab had a lower total number of relapse events compared with patients on generic GA 20 mg (7.06 vs 9.79), irrespective of these relapses leading to hospitalization or not. The probabilistic sensitivity analysis confirmed the base-case results that alemtuzumab dominated generic GA 20 mg as patients accumulated lower total incremental costs (-$476,987; 95% CI: -$579,996 to -$379,029) and higher incremental QALYs (1.1379; 95% CI: 0.4230 to 1.8306). In a scenario where natural history data was sourced from the London Ontario dataset, alemtuzumab continued to be dominant (lower total incremental costs: -$212,222; 95% CI: -$260,900 to -$165,772, and higher incremental QALYs: 0.9442; 95% CI: 0.3635 to 1.5248). Alemtuzumab is a cost-effective disease-modifying therapy for the treatment of patients with RMS when compared with generic GA 20 mg. These findings could help informed disease management decisions for effective RMS treatment.

Multiple Sclerosis (MS) Relapse Rates and Healthcare Costs with Generic Glatiramer Acetate: a Retrospective Claims Analysis of US Health Plan Data (P3.2-040)

Multiple Sclerosis (MS) Relapse Rates and Healthcare Costs with Generic Glatiramer Acetate: a Retrospective Claims Analysis of US Health Plan Data (P3.2-040)

Trends In Coverage For Disease-Modifying Therapies For Multiple Sclerosis In Medicare Part D.

The high cost of multiple sclerosis (MS) disease-modifying therapies can negatively affect access for patients through increased payer restrictions and higher out-of-pocket spending. Our objective was to describe changes in pharmacy benefit coverage and cost-sharing amounts for MS disease-modifying therapies in the Medicare Part D program, using enrollment-weighted Prescription Drug Plan Formulary files for the period 2007-16. Among therapies available throughout the study period, the rate of prior authorization use increased from 61-66percent of plans to 84-90percent. The share of plans with at least one therapy available without limitations declined from 39percent to 17percent. The projected cumulative out-of-pocket spending for 2019 was $6,894. The therapy with the highest out-of-pocket spending was generic glatiramer acetate. Policy makers need to consider both access restrictions and a growing cost-sharing burden as potential consequences of high and rising drug prices for people with MS.

Cost-Effectiveness of Alemtuzumab in the Treatment of Relapsing Forms of Multiple Sclerosis in the United States

ObjectiveTo evaluate the cost-effectiveness of alemtuzumab compared with fingolimod, natalizumab, ocrelizumab, and generic glatiramer acetate 20 mg among patients with relapsing multiple sclerosis (RMS) in the United States. Study DesignMarkov model with annual periods from payer perspective. MethodsThe modeled population represented pooled patients from the CARE-MS I and II trials. Therapies’ comparative efficacy at reducing relapses and slowing disability worsening was obtained from network meta-analyses. Safety information was extracted from package inserts. Withdrawal rates, treatment waning, resource use, cost, and utility inputs were derived from published studies and clinical expert opinion. To project the natural history of disease worsening, data from the British Columbia cohort was used. ResultsAlemtuzumab dominated comparators by accumulating higher total quality-adjusted life-years (QALYs) (8.977) and lower total costs ($421 996) compared with fingolimod (7.955; $1 085 814), natalizumab (8.456; $1 048 599), ocrelizumab (8.478; $908 365), and generic glatiramer acetate (7.845; $895 661) over a 20-year time horizon. Alemtuzumab’s dominance was primarily driven by savings in treatment costs because alemtuzumab has long-term duration of response and is initially administered as 2 annual courses, with 36.1% of patients requiring retreatment over 5 years, whereas comparators are used chronically. In model scenarios where alemtuzumab’s long-term duration of response was assumed not to hold and therapy had to be administered annually, probabilistic sensitivity analyses showed that alemtuzumab remained cost-effective versus ocrelizumab at a willingness-to-pay threshold of $100 000/QALY in 74% to 100% of model runs. ConclusionsAlemtuzumab was a cost-effective therapy. Model results should be used to optimize clinical and managed care decisions for effective RMS treatment.

Demonstration of Equivalence of Generic Glatiramer Acetate (GA) Produced by Mylan to Copaxone® (P1.361)

Demonstration of Equivalence of Generic Glatiramer Acetate (GA) Produced by Mylan to Copaxone® (P1.361)

Demonstration of Biological and Immunological Equivalence of a Generic Glatiramer Acetate.

Background: In April 2015, the US Food and Drug Administration approved the first generic glatiramer acetate, Glatopa® (M356), as fully substitutable for Copaxone® 20 mg/mL for relapsing forms of multiple sclerosis (MS). This approval was accomplished through an Abbreviated New Drug Applica-tion that demonstrated equivalence to Copaxone.Method: This article will provide an overview of the methods used to establish the biological and immu-nological equivalence of the two glatiramer acetate products, including methods evaluating antigen-presenting cell (APC) biology, T-cell biology, and other immunomodulatory effects.Results: In vitro and in vivo experiments from multiple redundant orthogonal assays within four biologi-cal processes (aggregate biology, APC biology, T-cell biology, and B-cell biology) modulated by glati-ramer acetate in MS established the biological and immunological equivalence of Glatopa and Copaxone and are described. The following were observed when comparing Glatopa and Copaxone in these exper-iments: equivalent delays in symptom onset and reductions in “disease” intensity in experimental autoim-mune encephalomyelitis; equivalent dose-dependent increases in Glatopa- and Copaxone-induced mono-kine-induced interferon-gamma release from THP-1 cells; a shift to a T helper 2 phenotype resulting in the secretion of interleukin (IL)-4 and downregulation of IL-17 release; no differences in immunogenicity and the presence of equivalent “immunofingerprints” between both versions of glatiramer acetate; and no stimulation of histamine release with either glatiramer acetate in basophilic leukemia 2H3 cell lines.Conclusion: In summary, this comprehensive approach across different biological and immunological pathways modulated by glatiramer acetate consistently supported the biological and immunological equiv-alence of Glatopa and Copaxone.

Switching from branded to generic glatiramer acetate: 15-month GATE trial extension results

Background: Open-label 15-month follow-up of the double-blind, placebo-controlled Glatiramer Acetate clinical Trial to assess Equivalence with Copaxone® (GATE) trial. Objective: To evaluate efficacy, safety, and tolerability of prolonged generic glatiramer acetate (GTR) treatment and to evaluate efficacy, safety, and tolerability of switching from brand glatiramer acetate (GA) to GTR treatment. Methods: A total of 729 patients received GTR 20 mg/mL daily. Safety was assessed at months 12, 15, 18, 21, and 24 and Expanded Disability Status Scale and magnetic resonance imaging (MRI) scans at months 12, 18, and 24. The presence of glatiramer anti-drug antibodies (ADAs) was tested at baseline and months 1, 3, 6, 9, 12, 18, and 24. Results: The mean number of gadolinium-enhancing lesions in the GTR/GTR and GA/GTR groups was similar at months 12, 18, and 24. The change in other MRI parameters was also similar in the GTR/GTR and GA/GTR groups. The annualized relapse rate (ARR) did not differ between the GTR/GTR and GA/GTR groups, 0.21 and 0.24, respectively. The incidence, spectrum, and severity of reported adverse events did not differ between the GTR/GTR and GA/GTR groups. Glatiramer ADA titers were similar in the GTR/GTR and GA/GTR groups. Conclusion: Efficacy and safety of GTR is maintained over 2 years. Additionally, switching from GA to GTR is safe and well tolerated.

Multiple sclerosis. Generic glatiramer acetate--a step toward cheaper MS drugs?

A randomized, double-blind, phase III trial of generic glatiramer acetate has shown equivalent efficacy and safety compared with the approved formulation, Copaxone. The impact of approval of generic glatiramer acetate, however, will mainly depend on the pricing of the drug.

Rates of Adverse Events and Multiple Sclerosis Relapses Before and After Introduction of a Purported Generic Glatiramer Acetate in mexico: Results from a Large Patient Support Program in Mexico

Rates of Adverse Events and Multiple Sclerosis Relapses Before and After Introduction of a Purported Generic Glatiramer Acetate in mexico: Results from a Large Patient Support Program in Mexico

Demonstration of equivalence of a generic glatiramer acetate (Glatopa™)

Glatiramer acetate (GA) has been available under the brand name Copaxone® for nearly two decades. Recently, the US Food and Drug Administration (FDA) approved the first generic GA, Glatopa™, as fully substitutable for all indications for which Copaxone 20mg is approved; Glatopa also represents the first FDA-approved “AP-rated,” substitutable generic for treating patients with MS. Glatiramer acetate is a complex mixture of polypeptides and, consequently, its characterization presented challenges not generally encountered in drug development. Despite its complexity, and without requiring any clinical data, approval was accomplished through an Abbreviated New Drug Application in which equivalence to Copaxone was evaluated across four criteria: starting materials and basic chemistry; structural signatures for polymerization, depolymerization, and purification; physicochemical properties; and biological and immunological properties. This article describes the rigorous overall scientific approach used to successfully establish equivalence between Glatopa and Copaxone, and presents key representative data from several of the comprehensive sets of physicochemical (structural) and biological (functional) assays that were conducted.

Similar Local Tolerability Profiles Following Double-Blind Treatment With Generic or Branded Glatiramer Acetate in Multiple Sclerosis (P3.256)

Similar Local Tolerability Profiles Following Double-Blind Treatment With Generic or Branded Glatiramer Acetate in Multiple Sclerosis (P3.256)

Randomized, double-blind, cross-over trial of GTR (generic glatiramer acetate) in healthy volunteers shows similar tolerability and safety to copaxone®

Randomized, double-blind, cross-over trial of GTR (generic glatiramer acetate) in healthy volunteers shows similar tolerability and safety to copaxone®

Launch of generic glatiramer acetate likely in 2014

Launch of generic glatiramer acetate likely in 2014

Japan: Dainichiseika & Milliken — plastics masterbatch

This review article describes the process which led to the discovery and development of a synthetic amino acid copolymer which we denoted copolymer 1, known now by its brandname Copaxone and generic name glatiramer acetate (GA) for the treatment of relapsing-remitting multiple sclerosis (RRMS). The long road (28 years) from basic scientific research, through studies in the experimental animal model of multiple sclerosis (MS), experimental allergic encephalomyelitis (EAE), to phase I, II, and III clinical trials in MS patients culminating in US Food and Drug Administration (FDA) approval, is unfolded herein.The review also summarizes results from recent clinical trials and studies on the mechanism of action of Copaxone in multiple sclerosis, as well as indications for a therapeutic potential in other autoimmune diseases, graft rejection, and neurodegenerative diseases.Several properties make Copaxone unique: (1) it is the first polymeric drug in which the polymer is the active constituent; (2) it is distinct from the other currently approved drugs for the treatment of RRMS (β-interferons: IFNs) by its specific immunomodulating activity; and (3) it combines in its activity immunomodulating as well as neuroprotective effects. It is a prototype for other autoimmune therapeutic vaccines.The cumulative clinical data demonstrate that Copaxone is effective in reducing the clinical (relapse rate and disability) and magnetic resonance imaging (MRI) activity in patients with RRMS, and that it has a sustained efficacy and tolerability for over 10 years. This, together with its favorable side effects profile, makes Copaxone perceived as a first-line therapeutic option and presently one of the most widely prescribed treatments for patients with RRMS.