Biosimilars as antivirals: opportunities and challenges

KEYWORDS:

• Biosimilars
• antivirals
• infectious diseases
• anti-infective therapy

1. Introduction

Antiviral drugs are specifically designed to treat viral infections, but they face various obstacles that pose significant challenges. In contrast to antibiotics, the range of antiviral drugs remains very limited. This scarcity arises because viruses represent much more complex targets than bacteria. Viruses reside inside our cells and depend on our proteins to meet their requirements, making them elusive targets. Therefore, eliminating the virus without causing harm to the host cell poses an enormous challenge [1]. The recent coronavirus pandemic (COVID-19) is a prime example of the urgent need for effective antiviral drugs. COVID-19, caused by the SARS-CoV-2 virus, rapidly evolved into a global health crisis, illustrating how contagious viruses can quickly lead to a pandemic. The impact of COVID-19 underscores the importance of developing new antivirals that are both effective and accessible. Developing these drugs from scratch is an expensive and time-consuming process, and the high cost of many antivirals limits their affordability, highlighting the need for more cost-effective options. Another critical issue in antiviral therapy is the development of resistance, where pathogens undergo genetic and protein modifications, becoming unaffected by existing drugs, posing a significant challenge [1].

Biological treatments have brought about a significant transformation in the management of various medical conditions. Many biologic patents and exclusivity periods are approaching their end or have already concluded. This has spurred the creation and authorization of products referred to as ‘biosimilars,’ which closely resemble licensed biologic therapies [2]. According to the NHS England, a biosimilar drug is ‘a biological medication that has been demonstrated to possess no significant clinical differences from the original medicine in terms of quality, safety, and efficacy. When NICE has previously endorsed the original biological medicine, the same guidance is typically extended to its biosimilar counterpart.’ [3]. The U.S. Food and Drug Administration (FDA) reported that biosimilars have been deemed as safe and efficient treatment choices for a range of health conditions, which include psoriasis, irritable bowel syndrome, Crohn’s disease, colitis, arthritis, kidney disorders, and cancer. Moreover, they can enhance the accessibility to lifesaving medications at potentially reduced expenses [4].

The prospects for addressing the challenges linked to antiviral drug use through the introduction of biosimilars are quite encouraging. Biosimilars hold the potential to mitigate the obstacles typically associated with the development of novel antiviral medications, including cost, development timelines, accessibility, and the emergence of viral resistance. This positions them as more personalized and effective treatment modalities and promising competitors in the battle against viral infections, which represent a paradigm shift in viral infection management. Hence, this editorial aims to discuss the opportunities and challenges confronting biosimilars as antiviral agents.

2. Biosimilars as antivirals: opportunities

Biosimilars have received recognition as safe and effective treatment choices for a variety of medical conditions. In 2023, the FDA granted its approval to Tyruko (Natalizumab-SZTN) and Yuflyma (Adalimumab-AATY), both of which serve as biosimilars to the original biologic medications, Tysabri (Natalizumab) and Humira (Adalimumab), respectively. There are currently 42 biosimilars approved by the FDA [5]. Nonetheless, as of now, Bioferon stands as the sole approved biosimilar product for addressing viral infections such as hepatitis C, while ongoing investigations are exploring the potential for other biosimilars in this therapeutic area [6]. It is important to highlight that one of the primary benefits associated with biosimilars is their potential to generate cost savings. For example, consider the conventional approach to treating hepatitis C, which involves using recombinant interferon alpha in conjunction with ribavirin [7]. However, recent advancements in HCV therapy have introduced drugs that directly target viral molecules. These drugs offer potentially less burdensome treatment options. They are called direct-acting antivirals (DAAs) because they specifically target proteins in the HCV life cycle, disrupting the virus’s ability to replicate and infect new cells. Conventional therapy can be extremely expensive, sometimes costing up to a thousand dollars per pill. This poses a challenge for patients seeking access to treatment [8]. Fortunately, biosimilars provide a cost-effective alternative. In trials, biosimilars like Bioferon (a biosimilar of Interferon Alfa) combined with ribavirin have shown effectiveness in treating adults with hepatitis C. The introduction of DAAs represents an advancement in HCV treatment by offering a targeted approach and often providing a cure for the disease [9].

Prior research assessing the response to various conventional interferons in patients with chronic hepatitis C indicated that Bioferon yielded the highest end-of-treatment response and maintained a virological response in most participants [10].

Biosimilars, especially when used in therapy, work in ways that closely resemble their reference biologic drugs. Typically, they primarily focus on targeting proteins or enzymes that are essential for the life cycle of the virus [11]. For example, in the case of viruses like SARS-CoV-2, biosimilars can inhibit enzymes such as RNA-dependent RNA polymerase (RdRp), which plays a vital role in viral replication. Examples of RdRp inhibitors are remdesivir and molnupiravir, which either stop RNA synthesis prematurely or cause mutations that render the viruses nonfunctional. Similarly, for treating HIV, biosimilars may aim at the viral integrase enzyme, responsible for integrating the genome into the host DNA. Additionally, another common strategy against infections like HIV and hepatitis C involves targeting proteases that play a role in processing viral polyproteins [11]. The inhibition of the release of viruses from host cells is also a technique employed to counter influenza virus infections.

To explore opportunities for development in antiviral therapy, it is essential to consider a wide range of biological sources, including marine algae. One interesting avenue of research involves studying compounds derived from green algae called Caulerpa racemosa, which shows potential as agents against SARS-CoV-2. By using docking and dynamics simulation techniques, this study has uncovered prospects for utilizing these compounds in the fight against viral infections like COVID-19 [12]. These innovative approaches highlight the potential of biosimilars derived from underutilized natural resources, opening up new pathways for combating viral illnesses. This example, coupled with approaches like those used in hepatitis C treatment, demonstrates the diverse possibilities in biosimilar development and their significant role in current and future antiviral therapies.

Overall, biosimilars represent a paradigm shift in medical treatment, offering not only cost-effectiveness but also a gateway to innovative therapies. Their development harnesses cutting-edge scientific advancements, leading to more personalized and effective treatment modalities. These products embody the progress in biotechnology, enabling the exploration of novel therapeutic agents from diverse biological sources, including marine ecosystems. This advancement in biosimilars opens the door to groundbreaking treatments, potentially transforming patient care in various medical fields.

3. Challenges

The development and use of biosimilars as antivirals, while meeting a fast-increasing demand, face several challenges that impact their adoption and effectiveness. One of the primary challenges is the requirement for extensive characterization to demonstrate high similarity in efficacy and safety to the original product, as mandated by regulatory agencies like the FDA and the EMA. This is a considerable challenge because even minor discrepancies in the production process can result in variations in the end product. Alongside this, assessing the immunogenicity of biosimilars is vital. This involves monitoring the development of antibodies and cytokine levels to establish clinical immunogenicity endpoints.

Conducting multiple head-to-head studies, often involving patients who have previously received the biosimilar, is necessary to compare it with the reference product. Post-approval, entering the market poses its own set of challenges for biosimilars. They may face competition from original products, and the reimbursement policies can significantly affect their usage. Furthermore, while biosimilars like Bioferon have shown effectiveness in treating chronic hepatitis C, there is a lack of long-term data supporting their safety and effectiveness, adding to the challenges in their widespread adoption [13].

4. Expert opinion

Biosimilars have emerged as a game-changer in antiviral treatments. While they offer hope of surmounting some of the inherent challenges related to antiviral drug development and accessibility, their introduction also brings its own set of challenges. The current studies on biosimilars as antivirals demonstrate their immense potential. Bioferon, for instance, shows remarkable promise in treating chronic hepatitis C infections. However, this excitement must be tempered by their long and complex approval process, which ensures patient safety. Minor variations during manufacturing can compromise their integrity, making the pursuit of perfect replication an ongoing challenge. Biosimilars hold the potential to transform antiviral treatment landscapes. Their ultimate vision is twofold: significantly lowering costs to expand access to essential medicines and hastening development timelines by building upon established biologic treatments. It’s not just about potential cost savings; it’s also about expanding the range and speed of antiviral treatments available to patients. Though biosimilars present tremendous potential, there are significant gaps in our understanding of their long-term safety and efficacy. Comprehensive, extended-duration studies are essential to address these concerns and ensure their viability as alternatives. These rigorous evaluation standards, while necessary, come with their own time and cost implications. Additionally, the challenge of ensuring consistency in quality, purity, and potency between individual biosimilars adds another layer of complexity.

In the coming years, the adoption of biosimilars will likely rise significantly, driven by patent expirations for biologic treatments and a growing demand for more affordable therapeutic alternatives. This upward trajectory, however, must be accompanied by rigorous research, refined regulatory processes, and extensive public awareness campaigns. Bioferon’s effectiveness in treating chronic hepatitis C, especially when paired with ribavirin, stands out. Yet, data on the long-term safety and efficacy of treatments lasting more than a year remain limited. This gap in knowledge is crucial as it sets a precedent for understanding the potential long-term implications of biosimilars.

5. Conclusion

Biosimilars offer hope in the realm of antiviral treatments. By addressing the challenges associated with the development and accessibility of antiviral drugs, they pave new pathways for affordable and effective therapies. However, like all groundbreaking initiatives, biosimilars come with their own set of challenges. Ensuring their similarity to original biologics demands rigorous approval processes that can span years. Moreover, the absence of long-term safety and efficacy data for treatments extending beyond a year underscores the importance of continuous and thorough research.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

ASJ, SRH, and AZA have contributed equally to the study design development, data extraction, manuscript drafting and reviewing

Additional information

Funding

This paper was not funded.