Higher, Fewer Copaxone Doses Lowered Relapse Rates Over 7 Years
A higher dose of Copaxone (glatiramer acetate) given three times weekly over seven years led to sustainably lower relapse rates and slowed disability progression in multiple sclerosis (MS) patients, according to a long-term analysis of the GALA study.
The higher dose — 40 mg/mL — was generally well-tolerated with no new safety signals observed. These findings support the safe, long-term use of Copaxone in people with relapsing forms of MS, the scientists said.
The study, “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,” was published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.
Copaxone, marketed by Teva Pharmaceuticals, is an approved treatment for relapsing forms of MS that is administered via an under-the-skin injection.
The therapy was approved originally at an established 20 mg/mL daily dose, but results from the GALA Phase 3 clinical trial (NCT01067521) showed that a less-frequent dosing regimen (40 mg/mL given three times per week) had a similar efficacy and safety profile.
This dosing regimen also appears to reduce adverse side effects, lessen fatigue, and improve treatment adherence, patient satisfaction, and patient-reported mental health over one year, compared with the original 20 mg/mL dose.
GALA was designed to evaluate the safety and effectiveness of the 40 mg/mL Copaxone dose versus placebo over one year. Participants who completed the placebo-controlled part then were eligible to enter an open-label extension (OLE) study and continue receiving 40 mg/mL of Copaxone for several more years.
After three years, interim OLE results indicated similar rates of relapse and MRI findings between those first treated with Copaxone in the GALA study, called early-start patients (ES), and participants who switched from placebo to Copaxone in the OLE part, dubbed delayed-start (DS) patients.
However, long-term data on the safety and effectiveness of the 40 mg/mL dose are lacking.
In this report, scientists at Teva, with researchers at various academic sites worldwide, described the long-term effects of 40 mg/mL treatment for up to seven years in the GALA and OLE studies.
A total of 580 early-start patients and 261 delayed-start patients completed the entire GALA and OLE studies, with a median follow-up of 5.5 years. The median Copaxone exposure was 4.9 years, with 631 of participants (45%) receiving the therapy for more than five years.
The overall analysis revealed that the mean annualized relapse rate (ARR) was significantly lower in the early-start group than the delayed-start group (0.34 vs. 0.53) during the one-year GALA study. In contrast, from years two through seven, the mean ARRs were low and not significantly different between early- and delayed-start participants.
Early-start treatment extended the median time to first relapse by about six months compared with the delayed treatment group (4.9 years vs. 4.3 years). During the OLE alone, the time to first relapse did not differ between treatment groups.
Similar results were observed for the percentage of patients who remained relapse-free. While more patients in the early-start treatment group had no relapses in the first year, the percentages of patients who remained relapse-free over the entire GALA and OLE studies were similar regardless of treatment start.
Other measures, such as confirmed worsening disability lasting at least six months (6mCDW), and mean changes in disability, as determined by the expanded disability status scale (EDSS), were similar in both groups over the GALA plus OLE period and in the OLE part alone.
At the end of one year, the mean EDSS change was –0.09 in the early-start group compared to –0.06 in the delayed-start group, which “could be due to the patients being reasonably early on in their disease course,” the team wrote.
The 40 mg/mL dose was generally well-tolerated, with no new safety issues seen, including no safety signals in lab tests, heartbeat readings, or vital signs. More than 80% of those treated with 40 mg/mL during the OLE reported at least one adverse event (AE), with 11% experiencing a serious AE.
The most common AE was injection-site reactions (40%) and immediate post-injection reactions (12%), which were mild and consistent with the 20 mg/mL dosing regimen. Four study participants died, but each death was considered not related to Copaxone by the investigator and the study sponsor.
“In summary, treatment with GA40 [Copaxone 40 mg/mL] conferred clinical benefit up to seven years of the GALA study, resulting in sustained low ARR and rates of disability worsening,” the researchers wrote. “Results from this OLE of the GALA study further support the known safety profile and effective long-term use of GA40 in the [relapsing MS] patient population.”