Mallinckrodt Pharmaceuticals is an innovation-driven specialty pharmaceutical company focused on improving outcomes for patients with severe and critical conditions. Among the company’s most innovative areas of focus is regenerative medicine – cell therapy – and the development of potentially paradigm-changing treatments for patients with severe burns and other difficult-to-treat skin conditions. The U.S. Food and Drug Administration has also highlighted the value of cellular therapy through its Regenerative Medicine Advanced Therapy program under the 21st Century Cures Act.
Cell therapy represents a new way forward in medicine, yet its possibilities must be balanced, according to Sally Temple, Ph.D., of the University of Albany School of Public Health.
Dr. Temple was one of four thought leaders who recently spoke with Mallinckrodt’s Science and Technology (S&T) organization during a “Cell Therapy” symposium. This day-long event explored the current state of the regenerative medicine healthcare segment and new emerging technologies. That balance Dr. Temple mentioned comes with ensuring review, testing, repetition and rigor as new developments advance while preserving patient welfare and public trust.
Temple was joined by Lynn Allen-Hoffmann, Ph.D., Senior Vice President of Regenerative Medicine, Mallinckrodt; Jörg Gerlach, M.D., Ph.D., McGowan Institute for Regenerative Medicine; and Jacques Galipeau, M.D., University of Wisconsin School of Medicine and Public Health. The symposium provided an introduction to cell therapy and explored topics ranging from translational research challenges, the convergence of cell therapy and medical devices, how adult retinal pigment epithelial stem cells may be able to help address age-related macular degeneration to mechanistic analysis of mesenchymal stem cells (MSCs) for optimized use in clinical trials.
Regenerative medicine therapies are being developed with different types of stem cells, including adult and embryonic, as well as progenitor cells, such as those found in umbilical cord blood, and numerous other tissues and organs. For example, epidermis contains tissue-specific progenitor cells which form the thin skin tissue forming the outermost layer of a body’s surface, while MSCs are multipotent stromal[i] cells that can differentiate into a variety of cell types, including bone cells, cartilage cells, muscle cells and fat cells.
At a high level, regenerative medicine describes regenerating or replacing human cells, tissues or organs to regain normal, healthy function, Dr. Allen-Hoffmann shared, with four key elements needed:
-Robust basic science frameworks to assess risk to patient;
-Innovative therapies that are readily translated to the clinic;
-Drivers for early adoption, such as cost-effective bio-manufacturing and operating/procedure room-friendly packaging; and
-Level 1[ii] randomized controlled trial designs.
Given organs and tissues are complex, regenerative medicine presents technical challenges such as scalability to a clinically relevant size, strict control over the starting materials – including cell sources, whether autologous[iii] or allogeneic[iv] – and tolerability or integration with the patient.
There are also operational challenges, Allen-Hoffmann noted. These are three-fold: in manufacturing, where you need ready access to early phase clinical good manufacturing practice facilities; in quality systems, with a need to support a wide variety of technologies and where existing guidance documents may not directly apply; and clinically, where enabling partnerships for ready access to experienced clinical teams is important.
Perseverance is key, said Dr. Allen-Hoffman, as she shared perspective from Steve Jobs, who said, “I’m convinced that what separates the successful entrepreneurs from the non-successful ones is pure perseverance.” She emphasized that the patient must also remain at the center as cell therapy advancements are made: “The moment in which you see the patient’s need firsthand is a critically important moment. It is both tremendously powerful and a sustaining driver of innovation and ultimately deployment of new therapies.”
[i] Relating to or affecting an organ’s supporting tissue
[ii] Randomized controlled trial (RCT) a study in which patients are randomly assigned to the treatment or control group and are followed prospectively
[iii] Obtained from the same individual
[iv] Obtained from a genetically similar, but not identical, donor