Compassionate Use Program (CUP) Benefits Strategies In Rare Disease

Compassionate Use Program (CUP) Benefits Strategies In Rare Disease

By Davelyn Eaves Hood, head of medical & patient affairs, Rezolute, and Ana Tediosi, head of expanded access program strategy, WEP Clinical

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In part one of this series, we explored Rezolute’s unique circumstance in pursuing ersodetug, an investigational drug for treating congenital hyperinsulinism (cHI), and how it led to the pursuit of a compassionate use program (CUP). We also detailed some of the challenges, in general, for enrolling rare disease patients in a clinical trial.

Now, in part two, we’ll discuss the benefits of continuing patient care with a CUP and the best practices for implementing one.

The Benefits Of A Compassionate Use Program

While the initial rationale for initiating the CUP for Rezolute was both humanitarian and strategic in its support of recruiting the RIZE study, the downstream effects of launching a CUP make for a strong business case, particularly in the rare disease setting.

Benefits For Patients

A CUP is a large undertaking that may at first seem too daunting to consider for a small company with limited resources. Senior leadership may even be concerned that the cost and risks of CUP implementation may not offset the potential gains of the program. However, in the rare disease community where treatment options are limited, at best, or simply nonexistent for far too many, the earliest possible access to safe and potentially effective therapies serves as a literal lifeline to patients and families. Deciding to launch a CUP when there is sufficient evidence for safety and efficacy fosters a strong patient-centric corporate culture and builds trust with stakeholders and the community, most importantly with the patient community and the healthcare professionals (HCPs) that care for them.

Relationship-Building Opportunities

By definition, compassionate use requests come as physicians have frustratingly exhausted all available means to manage a patient’s serious life-threatening condition. Proactively establishing the infrastructure for a CUP enables the company to nimbly respond to requests as HCPs become more aware of the program through peer-to-peer interactions, publications, congress attendance, and other typical provider engagement strategies. While the primary intent is providing a potentially promising therapy to address the unmet needs of the patient, it also deepens the engagement with physicians through their hands-on clinical experience with the investigational therapy.

Value-Driven Strategy

At the point a therapy in development has sufficient proof-of-concept and safety data available and investigational drug quality and supply are secure, the risk/benefit analysis of providing the therapy under compassionate access should be considered. In contrast to the alternative of an open-label extension (OLE) study, CUPs are significantly more affordable per patient treated. CUPs may play a crucial role for patients with rare disease who have no remaining approved treatment options, even when only limited anecdotal evidence or mechanism of action theoretically supports an investigational therapy’s potential to treat a condition.1 In comparison to other proof-of-concept options such as investigator-led or clinical trials, a CUP presents a valuable strategic option to add supportive real-world data to the overall evidence package in the right set of circumstances.

Grows Evidence & Provides Clinical Insights

Real-world experience gained through a CUP can provide insights into a broader population than those typically selected for clinical trials, dosing refinement, clinical responsiveness, an expanded safety database, and supply/logistical experience. When comparing investigational program options, there is a trade-off in the ability to gather data, and until recently, clinical studies and OLE data were considered more acceptable in regulatory considerations. However, with the major regulatory agencies announcing guidelines around the use and acceptance of real-world evidence, CUP data is increasingly utilized to support data packages submitted to regulatory agencies and payers.2 A CUP also offers longer-term data generation and documentation of the safety and efficacy profile of a study drug than a time-bound study. By determining a small subset of key data elements necessary to demonstrate desired treatment outcomes, offering a simple mechanism to capture data from the outset, and monitoring CUP data collection with similar monitoring integrity as a clinical study, CUP data can be an effective means to support the evidence package at the time of filing as well as Market Access Reimbursement decisions.

Operationalizing A CUP

For a small biotech, CUP implementation is likely a completely new project where the internal team has little to no experience. At the outset of implementing a CUP, there needs to be a widespread cross-departmental understanding of the program and its goals that align with the right-sized investment from senior leadership. Up front, it is crucial to communicate timelines and the foreseeable workload the CUP will add across all departmental stakeholders. Commonly led by the medical affairs team, CUP execution should be viewed similarly to that of clinical trials, leveraging existing or building new cross-functional meeting structures to facilitate timely communication, proactive solutions, and the best chance for success.

Critical Success Factors:

Selecting the right CUP service provider

For a small biotech company involved in a global multicenter study with limited experience in starting and managing a CUP, it was crucial to choose the right CUP service provider. This partner needed to not only operate with expertise and efficiency but also align with our patient-centered culture. The chosen service provider had to facilitate our learning process and contribute the essential knowledge our team lacked regarding CUPs, thereby helping to shape our strategy and support operational implementation.

Scoping the program

Like any project or program, a CUP must be appropriately sized to address the expected near-term patient volume while anticipating growth over time. The team should strategically build operational capacity, establish broader treatment guidelines, and ensure a sufficient drug supply to capitalize on future opportunities for investigational products with potential applications across multiple indications.

Ensuring supply

This is an item important enough to mention twice. CUPs initiated during the precommercial phase of development must consider the competing drug product life cycle activities that are being undertaken by chemistry, manufacturing, and controls (CMC) colleagues transitioning drug product supply from clinical trial to commercial stock. It is essential to clearly define the volume of drug product available for CUP patients and identify any additional actions required by the drug supply team to maintain an updated and available supply. Understanding the timeline for supply availability is crucial for proper patient volume planning and to avoid treatment delays due to supply issues.

Capturing data

Different countries have varying regulations regarding data capture for CUPs. It is essential to prioritize and limit data collection to a few key elements recorded by the treating physician in a compliant and de-identified manner. Generally, capturing key disease and treatment information is feasible. Small site budgets can be established to compensate staff for time spent on data entry; however, in many compassionate use settings, sites often forgo payment instead of access to the investigational drug for their patients. Key elements to consider include disease history, investigational dosing information, concomitant medications, related adverse events and serious adverse events, relevant biomarkers aligned with clinical trial endpoints, and pertinent patient-reported or quality-of-life outcomes.

Conclusion

Drug development is an ever-evolving field, and patients with rare diseases should not be left behind. Currently, traditional stepwise drug development, while critical to the overall ecosystem to bring safe and effective therapies to market, is a slow process that leaves those impacted by rare disease on the sideline awaiting the day they finally access a desperately needed therapy.3 Sadly, also for rare disease, the wait is too long. The Rezolute CUP experience demonstrates that such programs are mutually beneficial for both patients and biotech companies. Ultimately, Rezolute’s CUP was a value-driven strategic investment that provided additional insights, helped build relationships with treating physicians, allowed the company to explore a new indication, built capacity around global CUP strategy and execution with the support of a reliable CUP service provider, and most importantly was transformative for patients. The data generated from a CUP has the potential to further drive more interest in an investigational drug in the form of publications, clinical trials, and shared patient experiences.

When a biotech company in the rare disease space adopts a patient-centered approach as an integral part of its strategy, it not only strengthens the business but also improves the lives of patients, especially those with critical and urgent medical needs. This approach can lead to better health outcomes, providing patients and their families with more quality time to share meaningful moments together. For this reason, CUPS must be considered essential to the development pathway for all involved in developing rare disease therapies.

Acknowledgments:

The authors extend our sincere thanks to Erin O’Boyle at Rezolute for her invaluable operational support of the CUP since its inception. We also wish to thank Gabby Sorenson Jones, Julia Waters, and Mona Salih at WEP Clinical for their dependable management of the Rezolute CUP project. In addition, we wish to recognize Jasmine Sidhu at Rezolute and the broader WEP team for their relevant input and review during the development of this white paper. Most importantly, we are grateful for the opportunity to offer ersodetug under compassionate use to patients, which has inspired our teams and provided meaningful insights about this investigational therapy.

References:

  1. Fountzilas, E., Said, R., & Tsimberidou, A. M. (2018). Expanded access to investigational drugs: balancing patient safety with potential therapeutic benefits. Expert opinion on investigational drugs, 27(2), 155–162. doi:10.1080/13543784.2018.1
  2. Polak, T. B., van Rosmalen, J., & Uyl-de Groot, C. A. (2020). Expanded Access as a source of real-world data: An overview of FDA and EMA approvals. British Journal of Clinical Pharmacology, 86(9), 1819-1826. doi:10.1111/bcp.14284
  3. Fernando, S. (2023). Rare Diseases Medicine: Advantages, Challenges, and Future Developments. PharmaFocus Europe(02). Retrieved September 16, 2024, from https://www.pharmafocuseurope.com/research-development/rare-diseases-medicine

About The Author:

Davelyn Eaves Hood, MD, MBA, BCMAS, is the head of medical and patient affairs at Rezolute, Inc., where she brings decades of leadership in rare disease advocacy and patient-centric healthcare administration. With a robust background in primary care and the U.S. payer system, Dr. Hood has been instrumental in advancing Rezolute’s rare disease drug development efforts, particularly in hyperinsulinism clinical trials, strengthening KOL engagement, and spearheading the creation of the company’s compassionate use program. As a rare disease parent, former Board President of Congenital Hyperinsulinism International, and previous, founding principal investigator of the HI Global Registry, Dr. Hood fosters collaboration between industry and rare disease community stakeholders to advance shared goals.

With over 10 years of experience in the pharmaceutical industry, Ana Paula Tediosi, MPharm is a recognized expert in the field of Expanded Access Programs (EAP). Her expertise lies in oncology, hematology, and rare diseases, and she has held various roles in Big Pharma (Roche, Menarini-Stemline), including leading asset transitions, commercial project lead, and pharmacovigilance and compliance. Throughout her career, Ana has consistently demonstrated strong communication skills and a proven track record of successfully driving projects in challenging and international environments. Her commitment to delivering the best healthcare solutions to patients is unwavering, and she is equally passionate about promoting gender equality in both business and society. Ana is currently based in Switzerland working as a Business Development Director and Head of Expanded Access Strategy at WEP Clinical.