By Stuart Bell, EVP Inceptua Early Access and Estelle Canazilles, Senior Program Manager, Inceptua Early Access

Antibiotic resistance is the third leading cause of death, globally, claiming almost 5 million lives every year, with this projected to increase significantly over the coming decades [1]. A recent article in The Lancet estimated that there is the potential to save 92 million lives between 2025-2050 by improving access to antibiotics [2]. The availability of products to treat AMR infections in low- and middle-income countries (LMICs) is approximately 100 times lower than in the US. Fewer than half of the new antibiotics that entered the market between 1999 and 2014 were made available in more than ten countries. Consequently, there is a disproportionate impact of AMR on people living in LMICs [3].

Inceptua has had the privilege of managing several programs for novel medications targeting drug-resistant pathogens, with a particular focus on LMICs. 

There are several challenges in providing Early Access to medicines for AMR infections, especially in LMICs:

• Generally, either a very broad, or undefined, geographic scope
• Urgency of delivery for patients who often are suffering from immediately life-threatening illnesses
• Country scope often includes LMICs or other countries with less well-developed healthcare systems
• LMICs often have scant regulations relating to early access
• Physicians in LMICs are often less familiar with early access pathways
• Patients may present in a variety of treatment settings, as opposed to the more focused settings found in ‘typical’ early access (e.g. trial sites, oncology centers, rare disease specialists)
• Aspects of consent, given that patients can be in an intensive care setting and unable to provide direct consent for treatment
• Marginalized populations (sex workers, drug users etc.) where compliance and follow up present obstacles
• Outbreak containment – ability to rapidly respond to localized outbreaks

To overcome these obstacles, Inceptua has deployed a number of approaches to implement its AMR-specific Early Access Programs:

• Given the frequently urgent nature of treatment, Inceptua has deployed its out-of-hours customer service to ensure physicians have a point of contact outside of normal working hours, to ensure product delivery within a very short timeframe, often <24hrs anywhere in the world
• Highly reactive regulatory support to establish clear, compliant pathways for unlicensed medicines provision within a very short timeframe
• Inceptua’s front line customer service teams are trained to support physicians who treat patients with AMR infections and may be unfamiliar with the early access request process, and carefully lead them through the country-specific processes they will need to go through in order to import medicine for a patient in need
• Retrospective approval. Given the urgency of treatment, receiving regulatory authority approval to import a medicine prior to importation may not be feasible. Inceptua’s regulatory team have put in place processes which allow the medication to be shipped and administered, whilst the approval process is being negotiated.
• In early access, it is typical that language-specific labelling (or PIL/SMPC) is required. Given the global, and urgent nature of such programs, Inceptua frequently utilizes a ‘universal label text’ approach, whereby one label suffices for all potential countries.
• Retrospective approval and pandemic/outbreak containment approaches require close alignment with the country’s regulatory agency. Inceptua’s regulatory team have worked together with regulatory agencies, anticipating where demand/outbreaks may occur and putting in place systems to support urgent delivery e.g. prospective stockpiling of product. Prospective stockpiling is a process agreed with individual regulatory agencies which allows Inceptua to store unlicensed medicines at specific hospitals (or a central facility), to be used at the site, or urgently couriered to another site within the country, as soon as a patient is identified. Such a process supports emergency use treatments, dramatically reducing shipment times. The specific regulatory approval for the patient in question is obtained post-treatment (in agreement with the regulatory authorities), and the stockpile replenished to maintain sufficient supply within the country for the anticipated demand.
• Inceptua’s supply chain set up is designed to be agile and adaptable, allowing it to flex to the specifics of the product and the disease in question. Having a global network of warehouses with the full range of storage conditions and labelling capabilities, allows Inceptua to design bespoke supply chain solutions, tailored to the specificities of the drug and disease in scope, reducing delivery times and creating more cost-effective solutions for our clients.

AMR infections present some significant obstacles to early access programs and urgent provision of medicines, but with experience and considerable planning during the set-up phase, such provision is feasible.

Inceptua is cognizant that the part it plays in addressing AMR is only a fraction of that of the manufacturers and NGOs who provide research and development, good antibiotic stewardship guidance, develop diagnostics, support educational activities and broaden access to anti-infectives.

References

1. Oxlade, C. Addressing the Antibiotic Emergency. Health: A Political Choice – Building Resilience and Trust. A Global Governance Project Publication. 2024.
2. GB2 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. Lancet 2024; 404:1199-226.
3. Balasegaram, M. How more than 50 million deaths could be prevented by increasing access to antibiotics. World Economic Forum. October 2024.