Long-term efficacy and safety of three times weekly dosing regimen of glatiramer acetate in relapsing multiple sclerosis patients: Seven-year results of the Glatiramer Acetate Low-frequency Administration (GALA) open-label extension study

Abstract

Objective Describe the long-term outcomes of early-start (ES) and delayed-start (DS) glatiramer acetate 40 mg/mL treatment three times weekly (GA40) for up to seven years in the Glatiramer Acetate Low-frequency Administration (GALA) study in patients with relapsing multiple sclerosis (RMS). Methods Patients were evaluated every three to six months. The primary efficacy endpoint was annualized relapse rate (ARR); additional endpoints were exploratory or post hoc. For efficacy, data from the entire exposure period were used for the ES and DS cohorts. For safety, exposure only under GA40 was considered. Results Of the patients who continued into the open-label extension (OLE), 580/834 (70%) ES and 261/419 (62%) DS completed the OLE. For the entire placebo-controlled and OLE study period, ARR was 0.26 for ES and 0.31 for DS patients (risk ratio = 0.83; 95% confidence interval [CI]: 0.70–0.99). ES prolonged median time to first relapse versus DS (4.9 versus 4.3 years; hazard ratio = 0.82; 95% CI: 0.6–0.96). OLE-only results showed DS patients experienced similar efficacy for relapse and disability outcomes as ES patients. Adverse events were consistent with the well-established GA safety profile. Conclusions GA40 treatment conferred clinical benefit up to seven years, resulting in sustained efficacy and was generally well tolerated in RMS patients.

In vivo degradation forms, anti-degradation strategies, and clinical applications of therapeutic peptides in non-infectious chronic diseases

“…Clinical data from the European, American, and Canadian trials indicate that Copaxone® is an effective therapeutic that can decrease the frequency of MS relapse (Comi et al, 2001;Ford et al, 2010). Copaxone is injected subcutaneously along with the inactive ingredient mannitol that acts as a vehicle (Corominas et al, 2014;Rieckmann et al, 2021).…”

Therapeutic Advances in Multiple Sclerosis

“…Long-term outcomes for up to seven years for relapsing MS patients enrolled in the Glatiramer Acetate Low-frequency Administration (GALA) study demonstrated a 0.26 adjusted annualized relapse rate in the early-start GA group (randomized to GA in the placebo-controlled trial) compared to 0.31 in the delayed start GA group (switched to GA in the open label phase), with a risk ratio of 0.83 (95% CI 0.70-0.99, p = 0.04) with no differences between the two groups in terms of EDSS (expanded disability status scale) progression (36). The longterm safety profile was similar to those reported in the clinical trials, with the most common being injection site reactions (40%) and immediate post-injection reactions (12%); 11% patients had serious adverse events with 4 deaths that were deemed not related to the treatment drug (36).…”

Early use of high-efficacy therapies in multiple sclerosis in the United States: benefits, barriers, and strategies for encouraging adoption

“…Clinical trials of patients with RRMS have revealed comparable reductions in ARR for IFNs, glatiramer acetate, and teriflunomide and largely similar effects on time to first relapse for IFNs and glatiramer acetate (Table 1 ) [ 40 , 43 – 46 , 57 , 58 ]. Both teriflunomide and IFN therapy have been reported to delay disability progression [ 43 , 46 , 59 , 60 ], whereas glatiramer acetate appears to have no significant impact other than a potential stabilizing effect of long-term disability progression in patients with mild disease activity [ 45 , 53 ].…”