In which countries is Sotrovimab approved?

Introduction to Sotrovimab
Sotrovimab is a recombinant human monoclonal antibody developed by Vir Biotechnology in collaboration with GlaxoSmithKline. It is designed to target a highly conserved epitope on the spike protein of SARS‐CoV‐2, thereby neutralizing the virus and reducing its ability to enter host cells. This therapeutic agent was engineered to provide a high barrier to viral resistance and has shown activity against multiple variants of the virus. In the context of the COVID-19 pandemic, sotrovimab has been an important therapeutic option for treating patients who are at high risk of progressing to severe disease. Its development and subsequent regulatory evaluation illustrate the rapid response by the biopharmaceutical industry to the evolving global health emergency.

Mechanism of Action
Sotrovimab binds to a conserved region within the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. By doing so, it prevents interaction with the human angiotensin-converting enzyme 2 (ACE2) receptor, which is crucial for the virus’s entry into host cells. Its mechanism of action is further enhanced by modifications in the Fc region that extend its half-life and potentially recruit immune effector functions. This dual action of direct neutralization and immunomodulation helps reduce viral load and mitigate the progression of COVID-19 in infected patients.

Clinical Uses and Indications
Clinically, sotrovimab is used to treat non-hospitalized patients with mild to moderate COVID-19 who are at high risk for severe disease progression, including hospitalization or death. The approved indications target adults and adolescents (typically those aged 12 years and above and weighing at least 40 kg) who have underlying risk factors such as older age, significant comorbidities, or immunocompromised status. It is administered as a single intravenous infusion (500 mg) and, in some clinical settings, via intramuscular injection. Its early use in the disease course is aimed at preventing deterioration and reducing the burden on healthcare systems.

Regulatory Approval Process
The global regulatory framework for drug approval involves stringent processes that ensure drugs are safe, efficacious, and of high quality before they reach the market. These processes typically involve phases of clinical trials, detailed submission of safety and efficacy data, and ongoing pharmacovigilance.

Overview of Drug Approval Processes
Drug approval processes vary by jurisdiction but generally include preclinical studies, multiple phases of clinical trials (Phase I–III), assessment of risk-benefit balance by independent experts, and final review by the respective regulatory agencies. In the case of COVID-19 therapeutics like sotrovimab, expedited procedures such as Emergency Use Authorization (EUA), conditional, provisional, or full marketing approvals have been widely employed to address the urgent need for effective treatments. These accelerated processes still require robust data and clear definitions of conditions of use.

Key Regulatory Bodies Worldwide
The key regulatory agencies that evaluate and approve drugs include:
• The European Medicines Agency (EMA) in the European Union (EU), which provides centralized approval for member states.
• The U.S. Food and Drug Administration (FDA), which grants emergency use authorizations (EUAs) and, in some cases, full marketing approvals.
• The Pharmaceuticals and Medical Devices Agency (PMDA) in Japan, responsible for approving drugs within the Japanese market.
• The Therapeutic Goods Administration (TGA) in Australia, which issues provisional or full approvals based on available evidence.
• The Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom (UK), which approves drugs for clinical use in the UK.
• Other national agencies in countries such as Saudi Arabia, Canada, and several Middle Eastern and Asian nations also play pivotal roles in evaluating treatments like sotrovimab.

Sotrovimab Approval Status
The approval status of sotrovimab has evolved quickly since its development. Different countries and regulatory authorities have granted various types of approvals such as full marketing authorizations, conditional approvals, and emergency use authorizations. These decisions are based on extensive clinical data and reflect the need for effective COVID-19 treatments within local regulatory frameworks.

Countries with Approval
Sotrovimab has obtained regulatory approval or authorization in several countries and regions around the world. The following provides a hierarchical view based on the types of approvals and the local circumstances:

• **European Union (EU):**
Sotrovimab has received full marketing approval in the European Union under the brand name Xevudy®. The EMA’s Committee for Human Medicinal Products (CHMP) issued a positive scientific opinion under Article 5(3) of Regulation 726/2004 and subsequently the drug was granted full approval on December 17, 2021. This approval applies to all member countries of the EU, and sotrovimab is being supplied via centralized procurement agreements and individual national authorizations.

• **United Kingdom (UK):**
The UK’s MHRA has approved sotrovimab for use in patients who are at high risk for severe COVID-19. As reported in the literature, the UK regulator approved sotrovimab for patients aged 12 years and over who do not require supplemental oxygen but are at high risk for disease progression. This approval demonstrates the UK’s commitment to provide effective early treatments to manage the COVID-19 burden.

• **Japan:**
In Japan, sotrovimab has been approved through the PMDA via the Special Approval for Emergency Pathway. The drug application number “30300AMX00434” was associated with clinical data supporting its use, and the product is marketed under names that include descriptions of its use for intravenous injection. This regulatory pathway is commonly used in Japan for treatments addressing urgent public health needs, ensuring that high-risk patients have access to the therapy.

• **Australia:**
The Australian Therapeutic Goods Administration (TGA) has granted provisional marketing authorization for sotrovimab. Under this provisional approval, the drug—sold under its brand name Xevudy®—can be used to treat COVID-19 patients. This provisional approval is based on promising efficacy and safety data from clinical trials, with the understanding that ongoing data collection will support continued use and potential transition to full approval in the future.

• **Saudi Arabia:**
Sotrovimab has also received conditional marketing authorization in Saudi Arabia. This regulatory decision reflects the health authorities’ evaluation of the benefit-risk profile of sotrovimab in the treatment of COVID-19 in a population that is at significant risk for disease progression. The conditional approval implies that while there is sufficient evidence for clinical use under specific circumstances, further data will be collected to ensure long-term safety and efficacy.

In addition to these key regions, sotrovimab is distributed through emergency use or temporary authorizations in several other countries. Although these approvals vary in legal status compared to full marketing approvals, they allow access to the drug under regulated conditions:
• **United States:** Sotrovimab was originally granted Emergency Use Authorization (EUA) by the US FDA for the treatment of mild-to-moderate COVID-19 in high-risk patients. However, due to changes in the pandemic landscape and variant prevalence, the EUA has been subject to regional limitations and revisions, and as such, it is not considered a full marketing approval in the United States.
• **Other Countries with Temporary or Emergency Authorizations:** Sotrovimab has been made available in several other countries—including Canada, Singapore, Switzerland, the United Arab Emirates, Bahrain, Brazil, Egypt, Italy, Kuwait, Oman, Qatar, and Thailand—through emergency or provisional authorizations. These arrangements are designed to offer rapid access to potentially life-saving treatments while ensuring that regulatory bodies maintain oversight through ongoing data monitoring.

Conditions of Use
The approvals of sotrovimab in these countries come with specific conditions tailored to the epidemiological context and the available clinical evidence:
• **Patient Population:** In most jurisdictions, sotrovimab is approved for use in patients aged 12 years and older, weighing at least 40 kg, who have confirmed mild-to-moderate COVID-19 and are at high risk for progression to severe disease. This high-risk classification typically includes patients with comorbidities such as diabetes, chronic lung disease, cardiovascular conditions, obesity, and immunosuppressive conditions.
• **Mode of Administration:** Sotrovimab is administered as a single dose of 500 mg via intravenous infusion, although some clinical trial protocols have also investigated an intramuscular route as an alternative. The approved route of administration is based on the formulation and clinical efficacy data submitted to regulatory agencies.
• **Usage Limitations:** Some approvals specify that sotrovimab is not to be used in hospitalized patients or in those requiring supplemental oxygen due to COVID-19. The approvals focus on early intervention in outpatient settings to maximize clinical benefit and minimize progression to severe disease. Additionally, some regions have restrictions based on the prevailing variant circulation; for example, the US FDA amended the EUA fact sheet to exclude regions where non-susceptible variants predominate.
• **Labeling and Post-Marketing Commitments:** Conditional and provisional approvals often come with requirements for further post-marketing studies and data collection to confirm long-term safety and efficacy. Regulatory bodies such as the TGA in Australia and the CHMP in the EU have stipulated ongoing monitoring and additional submit data in their approval letters to ensure that emerging evidence supports continued clinical use.

Implications of Approval
The approval of sotrovimab in multiple countries has important implications for the global management of COVID-19, as well as for the broader market and distribution strategies employed by pharmaceutical companies.

Impact on Treatment Strategies
The regulatory approvals of sotrovimab have enabled healthcare providers to incorporate this monoclonal antibody into treatment protocols for high-risk COVID-19 patients. In regions where full marketing approval has been obtained (such as the EU and the UK), sotrovimab is a key tool in preventing disease progression among outpatients.
• **Early Intervention:** The therapeutic window for sotrovimab is during the early stages of COVID-19, and approvals emphasize its use before the onset of severe respiratory compromise. This is particularly significant in reducing hospitalizations, intensive care admissions, and mortality rates, as demonstrated in pivotal clinical trials.
• **Outpatient Management:** By targeting the outpatient setting, sotrovimab alleviates the pressure on hospital systems—a critical consideration during surges in COVID-19 cases. The approvals reflect a consensus among regulators that early monoclonal antibody intervention can lead to better clinical outcomes.
• **Variant Considerations:** The evolving nature of SARS-CoV-2 variants has influenced regulatory decisions, and approvals are often accompanied by guidelines on variant susceptibility. In many cases, the maintained neutralizing activity of sotrovimab against certain variants has been a key factor in its approval, despite concerns about reduced in vitro activity against newer subvariants.

Market and Distribution Considerations
The approval status of sotrovimab in diverse geographical regions has significant market implications:
• **Global Supply Agreements:** The fact that sotrovimab is approved in major markets such as the EU, UK, Japan, Australia, and Saudi Arabia facilitates global supply agreements. For example, Vir Biotechnology and GlaxoSmithKline have entered into procurement agreements with governments and international organizations to supply the drug across different regions, ensuring that high-risk patients worldwide have access to this treatment.
• **Access and Equity:** In many countries, especially those experiencing surges in COVID-19 cases, the rapid deployment of sotrovimab under emergency and provisional authorizations has been critical in addressing public health needs. However, equitable distribution remains a challenge, with some regions relying solely on emergency authorizations rather than full approvals.
• **Regulatory Harmonization:** The discrepancies between full marketing approval, conditional approval, and emergency use can complicate international distribution. Regulatory agencies have had to balance speed with safety, and the collaborative frameworks (such as the Joint Procurement Agreement in the EU) help streamline these efforts across multiple jurisdictions.

Future Developments
The regulatory journey for sotrovimab is not static; it is subject to ongoing review as new clinical data emerge and as the epidemiological landscape evolves. Future developments will address both clinical and regulatory research, and they have the potential to expand the drug’s indications and improve its efficacy profile in the context of emerging variants.

Ongoing Clinical Trials
Numerous ongoing clinical trials continue to investigate sotrovimab for broader applications and alternative dosing regimens. These studies are designed to assess:
• **Efficacy Against Emerging Variants:** Given the evolving nature of SARS-CoV-2, current studies are examining how well sotrovimab performs against newer subvariants, including those that may exhibit partial resistance to neutralization in vitro.
• **Alternative Administration Routes:** Trials comparing intravenous versus intramuscular delivery are underway, with the aim of improving ease of administration while maintaining efficacy.
• **Expanded Patient Populations:** Research is also focusing on the use of sotrovimab in special populations such as immunocompromised patients, pregnant women, and pediatric cohorts. These studies will provide more granular data on safety, dosing, and efficacy in groups that have historically been challenging to study.
• **Combination Therapies:** Given the potential for resistant viral mutations, studies are exploring the use of sotrovimab in combination with other antiviral agents to optimize therapeutic outcomes and mitigate the risk of resistance development.

Potential for Expanded Use
As new data become available, there is potential for the regulatory indications of sotrovimab to be expanded. This might involve:
• **Broadening the Indication:** Should ongoing trials demonstrate further benefits, sotrovimab could potentially be approved for a wider range of patient populations, including those with moderate to severe disease if used in combination therapies or in specific clinical scenarios.
• **Refinement of Treatment Guidelines:** Regulatory bodies may refine the conditions of use for sotrovimab based on real-world evidence. Such refinements could include adjustments to dosing guidelines, administration routes, or even broader preventative indications (for instance, in prophylactic use among immunocompromised individuals).
• **Long-term Safety and Efficacy Data:** The accumulation of post-marketing data will convince stakeholders regarding the long-term benefits and safety profile of sotrovimab. This data is essential for converting provisional or conditional approvals into full, unrestricted marketing authorizations in all regions.

Conclusion
In summary, the approval status of sotrovimab is multifaceted and varies by region. It has received full marketing approval in the European Union under the brand name Xevudy® and has gained regulatory approval in the United Kingdom by the MHRA. In Japan, the PMDA approved sotrovimab through a Special Approval for Emergency Pathway, allowing its use among high-risk patients. Australia granted provisional marketing authorization through the TGA, ensuring access during the pandemic, while Saudi Arabia issued conditional marketing authorization based on the local risk-benefit assessment. Additionally, many other countries—including Canada, Singapore, Switzerland, the United Arab Emirates, Bahrain, Brazil, Egypt, Italy, Kuwait, Oman, Qatar, and Thailand—have implemented emergency or temporary authorizations that facilitate the controlled use of sotrovimab, although they may not equate to full marketing approvals.

The implications of these varied regulatory decisions are significant. They impact treatment strategies by ensuring timely access to effective therapies, especially in outpatient settings to prevent the progression of COVID-19. They also have a substantial influence on market dynamics, distribution logistics, and international supply agreements. Ongoing clinical trials and real-world studies promise to further refine our understanding of sotrovimab’s efficacy against emerging variants, potentially expand its approved indications, and ensure that its use is optimized for diverse patient populations.

Overall, the global regulatory landscape for sotrovimab illustrates a remarkable collaborative effort among regulatory agencies and pharmaceutical companies to address an unprecedented public health crisis. As more clinical data accumulate, further refinements in the approved indications, dosing regimens, and combination therapy approaches are expected. This continuous evolution will not only enhance patient outcomes but also guide future drug development strategies for emerging infectious diseases.

In conclusion, sotrovimab is approved for use in the European Union, United Kingdom, Japan, Australia, and Saudi Arabia, with many additional countries providing emergency or temporary authorizations. These approvals, granted under both full marketing and conditional frameworks, reflect the robust clinical evidence supporting sotrovimab’s efficacy in reducing COVID-19 progression among high-risk patients. The ongoing trials and post-marketing surveillance will continue to shape its role in the global treatment landscape, ensuring that healthcare providers worldwide have access to this critical therapeutic tool in the fight against COVID-19.