1. Please introduce yourself and tell us about your background spanning both academia and industry, particularly your role in the Transplant Therapeutics Consortium (TTC).
I am William Fitzsimmons, a pharmacist by training. My career started at an academic medical center in Chicago, Rush University, where I was involved in bone marrow transplant and liver transplantation. Subsequently I joined Fujisawa Pharmaceutical company, which became Astellas Pharma. At Astellas I focused initially on the clinical development of tacrolimus (Prograf) for transplant immunosuppression and was also involved in clinical studies of other pipeline immunosuppressants. At the end of my Astellas career, I was heading global Regulatory Affairs. After 29 years, I retired from Astellas and joined the Transplant Therapeutics Consortium to continue my passion for advancing new innovative therapies into transplant with a focus on regulatory science.
2. The TTC brings together the transplant community, industry members like Memo Therapeutics, and regulatory agencies. What is the importance of this collaborative approach?
As a public private partnership, the TTC brings various stakeholders together in a precompetitive space. This allows all parties to focus on addressing challenges that are not unique to one company or therapeutic but that can benefit the larger community. There is no other forum like this in transplantation. A key part of this for me are the relationships with regulatory bodies, ensuring these key medicines reach transplant patients who need them most. We have a formally assigned FDA CDER Liaison to facilitate direct interactions with the FDA.
3. What are the challenges of traditional endpoints for kidney transplant patients and why is developing new endpoints so critical for advancing transplant therapeutics?
The current endpoints were established in the 1990’s and reflected the challenges that existed 30+ years ago in the field. When applied to today’s innovative new therapies, these endpoints fail to address the issues that are critical to transplant recipients, i.e. new therapies that a) prolong the transplanted kidney graft life, b) improve the tolerability of the current therapies, and c) improve the quality of life for the transplant recipient. It is important for us to continually assess and improve the endpoints we use, to ensure we are making an impact in transplant patients’ lives.
4. Through your work with TTC members across the transplant ecosystem, what advice would you give to biotech companies about working effectively with the transplant community and regulatory agencies to successfully bring their therapies to market for diseases with significant unmet clinical needs?
It is vital to engage with transplant recipients to understand the needs and issues that they are experiencing. Having early and frequent discussions with the FDA and other regulatory authorities in conjunction with transplant recipients and the academic community ensures that everyone is hearing the same messages and can align. Another key point is to take advantage of regulatory pathways to address serious and life-threatening conditions (for the FDA this includes Fast Track Designation, Accelerated Approval using surrogate endpoints, and Breakthrough Therapy Designation).
5. Looking ahead, what other innovative approaches or tools does the TTC believe are needed to accelerate the development of new transplant therapies?
Everyone plays an important part in the therapeutic development process. Transplant recipients need to continue to advance their message and communication of needs and advocate for themselves and others. Academic centers need to help ensure that trials are performed in an efficient and cost-effective manner so that transplant development is attractive to companies from a time and money perspective relative to other therapeutic areas. Biopharma companies need to reassess the opportunities in transplant so that new innovation isn’t only targeted for non-transplant indications. Investors need to engage with the community to understand the financial opportunities and help derisk approaches. Regulators need to participate in forums such as the TTC to continue dialogue with all stakeholders and facilitate the approval of new therapies that are both safe and effective. Currently the TTC is focused on a new surrogate endpoint (iBOX) in kidney transplant for use in the FDA accelerated approval pathway. Future novel endpoints may include safety endpoints and/or patient reported outcome measures that can further demonstrate the superiority of novel innovative therapies.
