July 9, 2014: NCATS Collaboration Translates into Potential Treatment for Sickle Cell Disease

I often cite the essential components of translational science — collaboration, public-private partnerships, innovative research models — as common denominators of all NCATS initiatives. One of the most exciting parts of our work is when research teams demonstrate that these elements can produce breakthroughs in translation.

Our latest accomplishment is truly a historic one, producing two “firsts”: For the first time, efforts of researchers from NCATS’ Therapeutics for Rare and Neglected Diseases (TRND) program have culminated in the acquisition of a drug candidate by a biopharmaceutical company, Baxter International, to complete clinical development. And also for the first time, a drug targeting the underlying cause of sickle cell disease — the first genetic condition ever defined at the molecular level — has advanced into late-stage clinical development.

The project began in 2010, when TRND researchers signed a collaborative agreement with a small biotechnology company, AesRx, LLC — which Baxter recently acquired — to develop Aes-103 as a potential treatment for sickle cell disease. The project team included researchers from our TRND program; AesRx; and the National Heart, Lung, and Blood Institute. Prior to the collaboration, AesRx had been unable to secure private financing, essentially stalling the project. Without TRND, it is unlikely Aes-103 would have made it to patients in clinical trials.

TRND researchers are experts in preclinical drug development, and they focus solely on innovative approaches to advancing potential treatments for rare and neglected diseases to first-in-human trials, an approach known as “de-risking.” The aim is to scientifically and medically validate new drug candidates like Aes-103, which makes them more attractive to external partners who then invest in completing development, manufacturing and marketing.

The AesRx/NIH team worked together to develop Aes-103 through a successful Phase II clinical trial to evaluate safety and effectiveness. Baxter then acquired AesRx, including its Aes-103 development program, and the company will now perform the clinical development activities required for regulatory approval and commercialization.

People with sickle cell disease have defective hemoglobin (the protein in red blood cells that carries oxygen), causing cells to become rigid and crescent-shaped and leading to clots and blocked blood vessels. Despite knowing the genetic basis of sickle cell disease and having a molecular target for 65 years, no approved drugs directly target the defect. Aes-103, which binds directly to the defective hemoglobin, is the first compound specifically developed to address the underlying molecular mechanism of the disease.

This project could not be more important to NCATS, and more broadly to NIH, for a multitude of reasons, including that it:

  • Is the first TRND project to reach the ultimate goal of de-risking a drug candidate to the point of attracting commercial interest, an outcome that validates the program’s model.
  • Involved a close collaboration between NIH and industry, demonstrating that public-private partnerships like this one can move mountains.
  • Provides a potential therapeutic for a rare and neglected disease of paramount importance to U.S. public health and elimination of health disparities. (Sickle cell disease disproportionately affects African-Americans.)
  • Offers a compound that targets the molecular defect of the disease, alleviating the common failure to translate basic knowledge of a disease’s molecular mechanism into a treatment that specifically targets that mechanism.

This success vividly illustrates the compelling need and enormous promise of the NCATS approach we have developed. Now that we’ve demonstrated it works, we look forward to continuing to applying our model to the thousands of rare and neglected diseases that are currently untreatable and disseminating that approach to the research community.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences