OVER THE YEARS, the number of disease-modifying treatments (DMTs) approved to treat relapsing multiple sclerosis (MS) has increased exponentially, providing a range of options for the benefit of patients. As these therapies advance, the need for optimized treatment selection becomes even more important. Started in 2017, a randomized, parallel, non-inferiority phase 3 study (NCT05242133) aims to provide more clarity by comparing pegylated interferon, or peginterferon, beta-1a to interferon beta-1a (CinnoVex), 2 DMTs developed by CinnaGen, which is led by CEO Haleh Hamedifar, PharmD.1
The trial includes 168 people with relapsing-remitting MS who were randomly assigned to either peginterferon beta-1a at a subcutaneous dose of 125 μg every 2 weeks for 24 months or interferon beta-1a at an intramuscular dose of 30 μg for the same period. Like most MS trials, the primary objective is change in reduction in annualized relapse rates; however, this study further aims to verify the non-inferiority of peginterferon beta-1a. Secondary study objectives include reduction in the total number of newly enlarged T2 hyperintense lesions or brain MRIs, disability progression, and safety (FIGURE).
Peginterferon beta-1a was approved by the FDA 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, which means polyethylene glycol is attached to interferon molecules, allowing them to maintain biological effects in the body for longer periods of time and allowing less frequent dosing. The drug is usually titrated to 63 μg on day 1, 94 μg on day 15, and 125 μg – the full dose – on day 29.
The current sample of patients included in the trial are between the ages of 18 and 50, each with Expanded Disability Status Scale (EDSS) scores between 0 and 5 and at least 1 relapse occurs in the 12 months prior to onset of treatment. treatment. People with primary progressive, secondary progressive or relapsing progressive MS were excluded from the study, as well as those planning to become pregnant or currently breastfeeding, and those for whom MRI was contraindicated.1
In order to ensure compliance and safety, during the first 2 months of the study, at each monthly visit, a nurse is responsible for injecting drugs for the two intervention groups and trains all self-injecting patients. At the end of the first 2 months and until the end of the study, patients self-inject the drug in both groups.
The approval of peginterferon beta-1a is based on data from ADVANCE, a placebo-controlled study that randomized patients with relapsing MS 1:1 to placebo (n=500) or 125 μg of active treatment once every 2 weeks (n=512) or every 4 weeks (n=500). A total of 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 versus 0.256 (95% CI, 0.206-0.318) in the placebo group. 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 28% in the 4-week dosing group. Additionally, the risk of disability progression, as measured by the EDSS, was reduced by 38% in both peginterferon beta-1a groups. To date, the safety profile of peginterferon beta-1a is consistent. In ADVANCE, 83% of people 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 treatment-related adverse events were injection site reactions, flu-like symptoms, pyrexia, and headache.3
CinnoVex, a generic biosimilar form of interferon beta-1a, has been approved in Iran. This recombinant protein consisting of 166 amino acids has been shown in previous studies to prevent the progression of disability in patients with MS. A notable 2012 study compared CinnoVex to Avonex, Biogen’s biosimilar form of interferon beta-1a, with results indicating that CinnoVex may be a safe and effective alternative treatment. The decreases in EDSS were 1.05 (±0.24; P = 0.62) 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 = 0.46) and 0.16 (±1.06; P = 1.0) in the respective groups after 24 months.4