Peginterferon beta-1a, a pegylated form of interferon designed to maintain biologic effects in the body for longer periods, is being evaluated against CinnaGen’s interferon beta-1a formulation, CinnoVex.
OVER THE YEARS, the number of disease-modifying therapies (DMTs) approved to treat relapsing multiple sclerosis (MS) has grown exponentially, offering a range of options benefiting patients. As these therapeutics advance, the need for optimized treatment selection becomes even more important. Started in 2017, a phase 3 randomized, parallel, noninferiority study (NCT05242133) aims to provide more clarity as it compares pegylated interferon, or peginterferon, beta-1a against interferon beta-1a (CinnoVex), 2 DMTs developed by CinnaGen, which is led by CEO Haleh Hamedifar, PharmD.1
The trial includes 168 individuals with relapsing-remitting MS who were randomly assigned to either peginterferon beta-1a in a 125-μg subcutaneous dose every 2 weeks for 24 months or interferon beta-1a in a 30-μg intramuscular dose for the same period. Like most MS trials, the primary objective is change in reduction of annualized relapse rates; however, this study additionally aims to verify the noninferiority of peginterferon beta-1a. Secondary objectives of the study include the reduction in the total number of newly enlarging T2 hyperintense lesions or brain MRIs, the progression of disability, and safety (FIGURE).
Peginterferon beta-1a was FDA approved for patients with relapsing MS in August 2014 based on data from the 2-year, phase 3 ADVANCE trial (NCT00906399).2 The agent is a pegylated form of interferon, meaning that polyethylene glycol is attached to the interferon molecules, enabling them to maintain biologic effects in the body for longer periods and allowing for less frequent dosing. The medicine is typically titrated from 63 μg on day 1, to 94 μg on day 15, and to 125 μg—the full dose—on day 29.
The current sample of patients included in the trial are aged 18 to 50 years, with each having Expanded Disability Status Scale (EDSS) scores between 0 and 5 and at least 1 relapse occur in the 12 months prior to treatment initiation. Those with primary progressive, secondary progressive, or progressive relapsing MS were excluded from the study, as well as those considering becoming pregnant or currently breastfeeding, and those for whom MRI was contraindicated.1
With the aim of ensuring adherence and safety, in the first 2 months of the study at each monthly visit, a nurse is responsible for drug injection for both intervention groups and trains all patients for self-injection. By the end of the first 2 months and until the end of the study, patients self-inject the medication in both groups.
Peginterferon beta-1a’s approval was backed by data from ADVANCE, which was a placebo-controlled study that randomly assigned patients with relapsing MS in 1:1 fashion to either placebo (n = 500) or 125 μg of active treatment once every 2 weeks (n = 512) or every 4 weeks (n = 500). In total, 88% (n = 1332) completed the 48-week treatment period, with adjusted relapse rates of 0.397 (95% CI, 0.328-0.481) in the placebo group vs 0.256 (95% CI, 0.206-0.318) in the 2-week dosing group and 0.288 (95% CI, 0.234-0.355) in the 4-week dosing group.3
New lesions on MRI scans were reduced by 67% in the 2-week dosing group and by 28% in the 4-week dosing group. Additionally, the risk of disability progression, as measured by EDSS, was reduced by 38% in both peginterferon beta-1a groups. To date, the safety profile of peginterferon beta-1a has been consistent. In ADVANCE, 83% of those on placebo experienced adverse events (AEs), compared with 94% (n = 481) and 94% (n = 472) of those taking peginterferon every 2 or 4 weeks, respectively. The most common AEs associated with the therapy were injection-site reactions, influenza-like symptoms, pyrexia, and headache.3
CinnoVex, a generic biosimilar form of interferon beta-1a, was approved in Iran. This recombinant protein consisting of 166 amino acids has been shown in previous studies to prevent progression of disability in patients with MS. One notable 2012 study compared CinnoVex to Avonex, Biogen’s biosimilar form of interferon beta-1a, with results that indicated CinnoVex can be a safe, effective alternative treatment. Decreases in EDSS were 1.05 (±0.24; P = .62) in the Avonex group and 0.16 (±0.88; P = 1.0) in the CinnoVex group after 12 months, followed by decreases of 0.27 (±1.05; P = .46) and 0.16 (±1.06; P = 1.0) in the respective groups after 24 months.4