BETHESDA, Md.—“Rare diseases are in a chasm,” says Dr. Christopher P. Austin, director of the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). “We’re a catalyst. Having an organization that focuses exclusively on what everyone else is not doing builds a bridge that brings badly needed treatment for rare and neglected diseases closer to patients.”
That effort bore fruit recently as a drug candidate developed by NCATS and its collaborators to treat sickle cell disease was acquired by Baxter International’s BioScience business. The drug candidate, Aes-103, is the first specifically developed to target the underlying molecular mechanism of sickle cell disease by changing the structure of the protein. Baxter now will advance the clinical development activities required for regulatory approval and commercialization.
This is the first time a company has acquired a drug candidate developed with NCATS’ Therapeutics for Rare and Neglected Diseases (TRND) program resources. Baxter International recently acquired AesRx LLC of Newton, Mass.—the TRND program collaborator—including Aes-103. TRND and AesRx researchers worked together to develop Aes-103 through a Phase 2 clinical trial to evaluate safety and effectiveness. The trial data indicated that Aes-103 significantly reduced patients’ pain.
Sickle cell disease, a genetic blood disorder, affects millions worldwide, including approximately 100,000 people in the United States, with one out of every 500 African-Americans stricken by the ailment. Life expectancy for people with sickle cell disease is only to mid- to late-40s. Defective hemoglobin, the protein in red blood cells that carries oxygen, causes their cells to become rigid and crescent-shaped, blocking small blood vessels and causing inflammation, pain and strokes, and decreased blood flow. Aes-103 binds directly to hemoglobin and changes its structure, reducing the sickling of red blood cells.
Before AesRx’s collaboration with TRND researchers, and despite promising data on Aes-103, the company had difficulty securing private financing, because potential investors lacked interest in funding an early-stage project that was considered too risky. The company lacked the resources to complete preclinical and early clinical development. Currently, the only drug approved by the U.S. Food and Drug Administration (FDA) to treat sickle cell disease is hydroxyurea, a drug initially developed to treat cancer. As Austin points out, hydroxyurea can have harmful or undesirable side effects or a limited response.
He adds, “Sickle cell was the first disease to ever have its molecular cause discovered—more than 65 years ago—and now a potential treatment based on that discovery has at last been developed. This success validates the NCATS model, which is based on a novel collaborative approach that de-risks intervention development programs to enable private-sector investment. We look forward to applying this model to the thousands of rare diseases that are currently untreatable so that we realize the NCATS mission of getting more treatments to more patients more quickly.”
TRND researchers signed a collaborative agreement with AesRx in 2010 and established a project team made up of NCATS and AesRx scientists as well as a leading sickle cell disease clinical researcher at the National Heart, Lung and Blood Institute (NHLBI). Other key project collaborators received support through NHLBI grants, the NIH Clinical Center and its pharmacy and NCATS’ Bridging Interventional Development Gaps program. Aes-103 was licensed by AesRx from Virginia Commonwealth University in Richmond, where the compound was discovered.
“This illustrates the power of team science,” Austin says. In less than one year, the team completed the preclinical toxicology, chemistry, manufacturing, controls and regulatory studies necessary to support an Investigational New Drug (IND) application, which AesRx filed with the FDA. After IND clearance, Aes-103 moved into Phase 1 clinical trials in healthy volunteers and sickle cell disease patients in 2011 and into a Phase 2 trial in patients in 2013. The project results also helped AesRx obtain a Massachusetts Life Science Accelerator loan to support development of Aes-103.
“This project may never have reached clinical trials if not for the TRND program and its preclinical drug development expertise and novel approaches,” said Stephen Seiler, AesRx’s founder and former CEO. “We believe Aes-103 has the potential to be a breakthrough in the treatment of sickle cell disease. TRND’s support for AesRx has enabled us to bring that potential closer to realization.”
“Acquiring AesRx and this clinical development program is an important opportunity, as it complements Baxter’s established relationships and expertise in treating rare and challenging blood disorders,” said Dr. Ludwig Hantson, president of Baxter BioScience. “This investment reflects our continued focus on addressing high unmet clinical needs for patients with inadequate treatment options and no recent major clinical developments.”
“Now we’re going to apply what we’ve learned to other projects,” Austin concluded. “We’ve done our job and handed it off, and we look forward to seeing it completed.”