Biologics, Volume 3, Issue 2 (June 2023) – 4 articles

The SARS-CoV-2 virus has caused a catastrophic impact on the world for the past 3 years. The virus has now returned with the emergence of the Omicron (B.1.1.529) variant. Within two months of its first emergence in South Africa, Omicron became the most dominating SARS-CoV-2 variant around the world, being the cause of the majority of new infections at present. Omicron has presented with the greatest transmission rate of all the previous variants despite the presence of mass vaccinations and acquired immunity. Several monoclonal antibodies and mRNA vaccines have failed to produce desired effects owing to a large number of mutations present in the Omicron variant. The introduction of the booster dose of the present mRNA vaccines has proven to be a great addition to the therapeutic armamentarium against the Omicron variant. Immunocompromised patients including the elderly, cancer patients, organ transplant recipients, and those with multiple comorbidities have been at a greater risk of developing severe diseases since the pre-Omicron era. The emergence of Omicron again raised a threat against this population. The protection from severe disease and mortality rates through the utilization of multiple immunizations and monoclonal antibodies has been controversial in this subgroup of patients. Thus, designing large-scale studies to evaluate the effectiveness of monoclonal antibodies and vaccines in these patients can provide evidence-based recommendations to improve survival in this population. This article attempts to discuss the different subvariants of Omicron, differences in the mutational aspects along with the particular focus on the consequences of the Omicron infection in the elderly population with diverse comorbidities. Full article

The Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) continues to be a major cause of high mortality in the world. Despite many therapeutic approaches having been successfully developed, there is still the need to find novel and more effective therapeutic strategies to face the upcoming variants. Here, we will describe the potential use of aptamers, synthetic single-stranded oligonucleotides, as promising tools to target SARS-CoV-2. Since aptamers have been successfully developed against viruses, this review will focus on the latest selection approach method using artificial intelligence, the state-of-the-art in bioinformatics, and we will also summarize the latest discoveries in terms of aptamers against spike protein and other novel receptor proteins involved in SARS-CoV-2 entry and the use of single-cell transcriptomics to define novel promising targets for SARS-CoV-2. Full article

Background. Although biosimilars have been increasingly used over recent years, some concerns about a potential loss of efficacy and altered safety profile when switching from an originator to a biosimilar still exist. Interchangeability can be a challenge for dermatologists too. An extensive systematic review of published switching studies among originators and biosimilars was carried out in order to provide evidence regarding the effects derived from the switch in terms of efficacy and safety outcomes in real-life contexts. Results. Thirty-seven articles were included in this systematic review (14 studies related to adalimumab, 10 to etanercept, 12 to infliximab, and 1 each to adalimumab, etanercept, and infliximab). Studies were mainly carried out among European countries. Most of them were observational studies or register-based studies. The majority of studies enrolled patients diagnosed with psoriasis or psoriatic arthritis who underwent a single switch from the originator to the biosimilar. Overall, the studies’ results demonstrated that switching between adalimumab, etanercept, and infliximab originators and biosimilars is safe and effective in a real-life setting of patients with dermatological conditions. Only a few studies highlighted an increase in the risk of loss of efficacy as well as an increased rate of AEs, both of which were identified as the main causes of biosimilar discontinuation, probably associated with the well-known phenomenon of the nocebo effect. Conclusion. Switching from a biologic originator to its biosimilar is safe and effective. Only a few studies have evaluated the switch among biosimilars; thus, no firm conclusion can be drawn for this type of switch in terms of the efficacy and safety outcomes. Based on our results, we believe that biosimilars can be considered interchangeable with their reference products and that no additional switch studies are necessary to support switching among originators and biosimilars in clinical practice. However, the continuous monitoring of all biologics (both originators and biosimilars) in routine clinical practice is strongly needed given their peculiar safety profile. Full article

Reinventing approved therapeutic proteins for a new dose, a new formulation, a new route of administration, an improved safety profile, a new indication, or a new conjugate with a drug or a radioactive source is a creative approach to benefit from the billions spent on developing new therapeutic proteins. These new opportunities were created only recently with the arrival of AI/ML tools and high throughput screening technologies. Furthermore, the complex nature of proteins offers mining opportunities that are not possible with chemical drugs; bringing in newer therapies without spending billions makes this path highly lucrative financially while serving the dire needs of humanity. This paper analyzes several practical reinventing approaches and suggests regulatory strategies to reduce development costs significantly. This should enable the entry of hundreds of new therapies at affordable costs. Full article