Reformulating An In-Clinic IV To At-Home Injection Puts Patients At The Center

By Christopher J. Schaber, chairman, president, and CEO, Soligenix

Reformulation is often viewed as a technical or manufacturing decision — something that occurs later in development to improve stability, scalability, or life cycle management. Increasingly, however, it is becoming clear that formulation and delivery decisions can play a far more strategic role. In some cases, they can directly influence patient access, trial feasibility, and, ultimately, whether a therapy is viable in the real world.

This is particularly true in rare disease, where patient populations are small and every barrier to participation can have an outsized impact. In these settings, operational realities observed during early-stage trials can provide critical signals that shape development strategy moving forward.

One example comes from the development of an investigational therapy, SGX945, we initially evaluated as a short IV infusion in a Phase 2a study, which is now being reformulated for subcutaneous home-based administration. While the scientific rationale for the therapy remained consistent, the experience of running the trial revealed a fundamental misalignment between how the drug was delivered and how patients live with the disease.

When Scientific Rationale Meets Operational Reality

The therapy was originally developed and studied in an acute care oncology setting, where patients were already receiving treatment in a clinical environment. In that context, a short IV infusion was practical and relatively seamless. Patients were already in the hospital for radiation or chemotherapy, and adding a brief infusion to their treatment schedule did not introduce meaningful additional burden.

However, when the same delivery model was applied in a chronic rare autoimmune disease setting (for the treatment of aphthous ulcers in Behçet’s disease), the realities were very different. Patients were not already embedded in the healthcare system on a daily basis; they were living with a condition characterized by intermittent flares and managing their symptoms alongside work and other responsibilities.

Although the Phase 2a study was designed as a proof of concept and successfully demonstrated encouraging activity, the logistics of IV administration quickly emerged as a challenge. Even in a region with a higher prevalence of the disease, where patient identification was less of a barrier, enrollment proved more difficult than anticipated.

Patients needed to travel to clinical sites multiple times per week for infusions, often requiring several hours away from work or daily obligations. For individuals who had learned to live with their condition and manage symptoms as they arose, this level of disruption was not always practical or acceptable. In some cases, enrollment targets had to be adjusted because of these constraints.

These experiences reinforced an important point: Clinical efficacy alone does not determine whether a development approach is viable. Operational friction, particularly when it affects patients directly, can be just as important.

Patient Burden As A Development Signal

In chronic and rare diseases, the burden associated with treatment is a central factor in whether patients will initiate and adhere to therapy. Unlike acute care settings, where patients are often willing to accept intensive interventions for a defined period, chronic conditions require approaches that can fit into daily life over time.

For patients with Behçet’s disease, flares are unpredictable and can occur multiple times per year. Many patients become highly attuned to the early signs of a flare and develop strategies to manage symptoms while maintaining their routines. Introducing a treatment that requires repeated hospital visits can disrupt that balance, even if the therapy itself is effective.

These dynamics have direct implications for clinical trials. Recruitment can slow when participation requires significant time and travel commitments. Retention can also be affected if the treatment schedule is difficult to sustain. In rare disease, where eligible patients are limited to begin with, these factors can significantly impact study feasibility.

Rather than viewing these challenges as purely operational issues, it’s important that sponsors recognize them as potential signals that the delivery model may need to evolve.

Reformulation As A Strategic Pivot

In this case, the development team anticipated that IV administration would present challenges in a chronic setting but proceeded with the initial formulation to establish proof of concept before investing in reformulation. Once biological activity and safety were observed, the focus shifted to making the therapy more practical for patients.

Several considerations drove our decision to move toward subcutaneous administration. First, it allows for potential self-administration, reducing the need for clinic visits and enabling treatment to occur at home. Second, it aligns more closely with how patients manage chronic conditions, particularly those characterized by episodic flares. Third, it offers a more flexible approach that can be integrated into daily life without significant disruption.

Importantly, internal analysis and input from KOLs and clinicians who work closely with patients informed this decision. These stakeholders emphasized the importance of convenience, accessibility, and ease of use in determining whether a potential new therapy would be adopted in practice.

Broader trends in healthcare have also influenced this shift. For example, the increasing familiarity of patients with self-administered injectable therapies (through the recent ubiquitousness of GLP-1 inhibitors) has reduced some of the historical barriers associated with this route of administration, making it a more acceptable option across a wider range of indications.

Development And Regulatory Implications

While it may ultimately be the best decision for patients, reformulating a therapy mid-development is not a simple transition. It introduces new scientific, regulatory, and operational considerations that must be addressed before advancing to later-stage trials.

One of the primary challenges of this formulation change is demonstrating comparability between the original and reformulated versions. Differences in absorption, distribution, and overall pharmacokinetics must be carefully evaluated to ensure that the subcutaneous formulation delivers the intended therapeutic effect. This often involves a combination of preclinical work and bridging studies designed to compare the two delivery methods.

In practice, this can add time and complexity to the development timeline. Reformulation work, including manufacturing and early pharmacology studies, may take several months, followed by additional studies to establish dosing and comparability. Only after these steps are completed can sponsors confidently proceed to larger controlled trials.

While this does extend development timelines, the effort is worth it because these steps ultimately help de-risk later stages by ensuring that the therapy is both effective and practical for patients.

Balancing Efficacy, Practicality, And Patient Experience

The broader treatment landscape also underscores the importance of delivery considerations. Many existing therapies for inflammatory conditions involve trade-offs between efficacy, safety, and convenience. Some require chronic daily administration, while others involve periodic infusions or carry risks associated with long-term immunosuppression.

In this context, development decisions must balance multiple factors. It is not enough for a therapy to demonstrate activity; it must also be accessible, tolerable, and aligned with how patients manage their condition.

For therapies intended to address flare-based diseases, this means focusing on designing approaches that allow patients to manage symptoms without significant disruption; the goal is to improve clinical outcomes and ensure that treatment can realistically be used in everyday life.

Lessons For Sponsors

Several broader lessons emerge from this experience that may be relevant for other sponsors:

First, operational challenges observed during early trials should be viewed as strategic insights rather than logistical inconveniences. They can reveal fundamental misalignments between an investigational therapy and the patient population it is intended to serve.

Second, in rare disease, even small barriers can have significant consequences. Trial recruitment, retention, and long-term adoption are all dependent upon factors such as travel burden, scheduling, and ease of administration.

Third, patient centricity requires more than high-level philosophy statements. It must be reflected in concrete decisions about formulation, delivery, and trial design. Engaging with clinicians, patient communities, and advocacy groups early in development can provide valuable perspective on what matters most to patients.

Finally, reformulation should not be viewed as a detour. In some cases, it represents a necessary step toward optimizing a therapy for real-world use. Taking the time to align delivery with patient needs can strengthen both clinical development and long-term adoption.

About The Author:

Christopher J. Schaber has been the president and CEO and a director at Soligenix since August 2006. He was appointed chairman of the board in 2009. He also serves on the board of directors of the BioNJ and the Alliance for Biosecurity, as well as been a member of the corporate councils of both the National Organization for Rare Diseases (NORD) and the American Society for Blood and Marrow Transplantation (ASBMT). Prior to joining Soligenix, Dr. Schaber served from 1998 to 2006 as executive vice president and COO of Discovery Laboratories, Inc.. From 1996 to 1998, Dr. Schaber was a co-founder of Acute Therapeutics, Inc., and served as its vice president of regulatory compliance and drug development. Dr. Schaber received his B.A. from Western Maryland College, his M.S. in pharmaceutics from Temple University School of Pharmacy and his Ph.D. in pharmaceutical sciences from the Union Graduate School.