Stories of Technology, Innovation, & Entrepreneurship in the Southeast

For Dr. Alan Solomon, the longtime Professor at the University of Tennessee’s (UT) Graduate School of Medicine, the discovery that the 11-1F4 anti-amyloid fibril antibody could result in a novel form of treatment for those afflicted with AL Amyloidosis also began another 30-year journey that is only now about to wrap-up.

“For the 11-1F4 monoclonal antibody to be given to a patient, it had to conform to the Federal Drug Administration’s (FDA) stringent Good Manufacturing Practice (GMP) guidelines plus a host of other regulations as well as entail a substantial production cost,” Solomon explained. “This was beyond our capabilities, so I sought out biopharmaceutical companies that had the resources to manufacture a GMP-approved product.”

Like so many other inventors who have breakthrough technologies, he found the market size to be a deterrent.

“When I told them there were approximately 2,500 newly diagnosed cases yearly, they shook their heads and said, given it was so rare, it was not economically feasible for them to take on the project,” Solomon said.

Although discouraged, the UT researcher embraced the old adage, “When one door closes, another opens,” and the door that opened was one at the National Cancer Institute. The agency had just launched a new program named Rapid Access to Interventional Development (RAID) that could provide needed resources for investigators like Solomon whose projects had clinical potential.

He applied for RAID in 1998 to develop the 11-1F4 antibody as a therapeutic agent, and it was approved with high priority. Then, the train slowed once more, starting with the it was a mouse or foreign protein that could not be administered to a patient repeatedly without provoking an adverse. The solution was to convert the murine 11-1F4 antibody into at least a partially human form, but finding a company to do so took two years.

“The next holdup resulted from the FDA’s insistence that we had to show that the chimeric 11-1F4 antibody would actually bind to a patient’s amyloid deposits,” Solomon said. The solution entailed giving a patient with AL Amyloidosis an injection of the antibody attached to a positron-emitting radioisotope and then be imaged by Positron Emission Tomography coupled with Computed Tomography.

After securing Investigational New Drug IND) approval from the FDA and a grant to cover costs, 40 individuals came from or to Knoxville over the next two years as volunteer participants. Several more hold-ups further delayed a Phase I study before the FDA granted IND status to begin the study, nearly 18 years after the initial experiments with mice.

By that time, Solomon was planning for his retirement at the end of 2013, and the UT Medical Center was not the ideal place to conduct the Phase I clinical trial. He did, however, identify another physician-scientist named Dr. Suzanne Lentzsch at Columbia University Medical Center. That study was completed in 2017, and Phase II and III trials followed.

“Preliminary results from this last trial, which involved over 400 patients at multiple institutions in the U.S. and abroad, have indicated the added benefit of the antibody, especially those with cardiac involvement,” Solomon says.

He gives great credit to the UT Research Foundation for its consistent support throughout the long journey.

“In my role as a physician-scientist and discoverer of this antibody, I could not be more pleased and humbled if, indeed, it will improve the prognosis and render this disease non-fatal,” Solomon adds. For those with the disease, his dedication and persistence are something that they should not only appreciate but celebrate.

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