April 11, 2022: A Decade to Deliver Five Times More Treatments

More treatments. All people. More quickly. These are our three audacious goals for the next decade and, in this message, I’m focusing on the first one.

Estimates put the number of all known diseases at over 10,000, with about 7,000 of them defined as rare diseases. Only about 5% of them have a treatment or cure. With DNA sequencing, scientists are identifying hundreds of new rare diseases each year. The disease-to-treatment ratio is growing, not shrinking.

Although NCATS is small, our remit is broad. The Center was established to streamline and de-risk the therapy-development pipeline so new medicines can reach patients faster. As I shared in my vision for the next decade, our goal is to have a treatment in the pipeline for 25% of known diseases by 2032 — a fivefold increase over what we currently have. Here’s a brief look at how we can get there.

Driving Toward More Predictive Tools and Approaches

About 90% of the promising therapeutic candidates that enter clinical trials fail because the 2-D cell cultures and animal models — the current drug development approaches for safety and efficacy — don’t capture the complexity of human tissues and don’t translate well into predicting people’s response to candidate therapies. To build more predictive models, we’ve doubled down on developing models that mimic the structure and function of human tissues.

To make these models, we’re using tissue chips and 3-D bioprinting. Both technologies use human cells to generate 3-D models that recapitulate key functions of healthy and diseased tissues and organs. The platforms are highly adaptable, which means researchers can readily use them to model many diseases.

Experts estimate that tissue chips alone could reduce drug research and development costs by 10–26%. To date, researchers have developed a variety of tissue chips, and the next frontier is exploring how tissue chips could transform clinical trials. Through our new Clinical Trials on a Chip program, scientists are creating tissue chips from patients’ own tissues to test potential drugs for safety and efficacy, which could shorten the initial phases of clinical trials and help us better understand who is more likely to respond positively. Think of YOU on a chip!

For tissue chip and 3-D bioprinted models to be widely used to develop new treatments, they must clear important regulatory hurdles. To this end, we’ve worked closely with the U.S. Food and Drug Administration on how the models can qualify as approved drug development tools. It is exciting that two NCATS-funded tissue chip models recently opened the door to clinical trials testing a drug for inflammatory lung diseases, including COVID-19, and a drug for a rare muscle disease.

Enabling Treatments Targeting What’s Common Across Diseases

At the current one-disease-at-a-time pace of drug development, it’ll take thousands of years to have treatments for all known diseases. We can tackle many diseases in parallel by taking advantage of their common features.

I previously mentioned that gene therapy is a promising treatment approach for many rare diseases because about 80% of them are caused by alterations in a single gene. However, gene therapy development is complex, costly, and proprietary. These barriers lead to one-off gene therapies, restrict research efforts, and minimize commercial interest. Two NCATS-led programs aim to revolutionize the approach.

The PaVe-GT program is testing the same gene delivery system and manufacturing methods for multiple rare diseases. Its NIH-wide research team seeks to standardize the gene therapy clinical trial startup process and publicly share results and related documents to spur similar gene therapy efforts. For example, the PaVe-GT team recently received an orphan drug designation from the FDA for one of its investigational gene therapies and plans to post its successful application to help other groups prepare their own.

The efforts of the Bespoke Gene Therapy Consortium (BGTC) are broader in scope and, as noted in an NIH Director’s Blog post, build on the PaVe-GT work. BGTC scientists want to better understand the biology of viral vectors to deliver genes, improve gene delivery system manufacturing, and streamline the path from animal testing to human clinical trials. Since the BGTC’s launch last fall, the public-private partnership has welcomed additional organizations, and it is currently reviewing community nominations for rare diseases to study.

Honing Artificial Intelligence/Machine Learning (AI/ML) and Data-Driven Technology Solutions

To bridge the data silos that slow drug discovery and development, NCATS has invested heavily in organizing, aggregating, and harmonizing quality data and making them available openly and responsibly. This strategy enabled our rapid COVID-19 response, which included curating and sharing real-world data through resources like the NCATS National COVID Cohort Collaborative, the OpenData Portal, and CURE ID. But open and accessible data on its own is not enough. We must turn big data into new knowledge — and new treatments. This shift is particularly critical for drug design.

More than 99.9% of the chemical space that contains biologically active compounds remains unexplored. To efficiently mine it for new medicines, NCATS is actively developing an end-to-end informatics solution nicknamed ASPIRE. It uses AI/ML capabilities to find algorithms and methods that will broaden our repertoire of druggable targets and probes, which we then can use to design promising new chemical molecules for biological testing in an autonomous manner. We’re demonstrating the feasibility of the approach through the ASPIRE Challenges, which is focused on finding new and improved treatments for pain, opioid use disorder, and overdose and funded through the NIH Helping to End Addition Long-term® Initiative, or NIH HEAL Initiative®.

To truly change lives, these approaches must lead to new treatments that reach the people who need them the most. Getting treatments to all people is another crucial part of NCATS’ vision that I will cover in an upcoming director’s message.

Your partner in science and health,

Joni L. Rutter, Ph.D.
Acting Director
National Center for Advancing Translational Sciences