Drug development

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Twelve years. That’s the average amount of time it takes for a viable therapeutic to make it from the research stage to approval for market. In that time, 2.4 million Americans will suffer the effects of severe acute pancreatitis, many of which can be long-lasting and debilitating. Roughly 240,000 of these patients will die as a result of the illness. This is from just one potentially treatable disease.

With more Americans falling ill to preventable diseases each year, the pressure has never been greater for researchers and developers to find ways to create higher-quality therapeutics in less time to save and improve lives. Surprisingly, the way forward is not to change the approval process but to improve the research and development methods applied at each pipeline stage.

The logjam isn’t the approval process — it’s the methods

At first glance, it is easy to assume that the logjam preventing therapeutics from getting to market lies within the approval process itself. After all, most research and development teams start out playing a long game in pre-clinical trials, which often last 3.5 years, or longer if trials do not go as planned. The same is true of Phase 1, Phase 2 and Phase 3 clinical trials, requiring one, two and three years respectively. Do the math, and you will find that the trial phases alone take nearly 10 years to complete. Understanding why this happens is the first step in reducing timelines to accelerate the pipeline.

Most drugs that never make it to market fail either just before or during the pre-clinical trial phase. In fact, for every 1,000 drugs that enter pre-clinical trials, just one advances to human clinical trials. This isn’t because 999 drugs are unsuitable for therapeutic use. In a significant number of cases, drug failure occurs due to poor reproducibility borne of mistakes in the early stages of development. Mistakes can happen in nearly every step of a study or trial and often result from flaws in the study design or human error impacting data collection, computation and results analysis.

This points to a disconnect between research and development. In academia, interesting and exciting results and discoveries are regularly published, but this does not mean that the results of these studies are reproducible once picked up for commercialization by drug developers. Over the past decade, drug developers have been more vocal about their inability to reproduce therapeutic research results. A 2018 study indicated that just 31% of medical research projects were reproducible at the pre-clinical trial stage. While the same study reported reproducibility of 75% of projects that make it to Phase 1 clinical trials, a recent study from MIT indicates that just 14% of drugs that make it to clinical trials will eventually be approved for market where they can actually help patients.

Each misstep in the development and execution of a research study or associated drug trial determines whether or not an otherwise viable therapeutic will reach the patients who need it in time to make a difference, or in many cases, at all. The way forward starts with helping researchers to think more like business developers.

Translational research solves research problems before they begin

Translational research aims to take exciting and promising academic research and help make it available for patient use.

Typically, business development methods are applied to therapeutics long after academic research is published. In translational research, the needs of go-to-market pipelines should be applied as early as possible in the research process. In drug development, this includes improving reproducibility rates at every stage of research and using business best practices from the beginning of the project to final approval.

One of the simplest but most crucial research best practices applied in translational research by my company, Lamassu Pharma, is the process of blinding pre-clinical trials in the same manner as human clinical trials. Traditionally, blinding has not been applied in pre-clinical studies because blinding intends to remove the potential for bias regarding any individual human study participant, and pre-clinical studies do not involve human subjects. Although not commonly recognized, bias can also be held against any individual animal subject in a pre-clinical study. Blinding the pre-clinical study removes all potential for bias, ensuring impartiality in analysis.

This one change immediately ensures study integrity, but alone is not enough to ensure reproducibility. Removing the potential for human error also plays a crucial role in providing study results that can be reproduced at every stage of drug development, which is the key to market approval. Simple solutions to eliminate human error include software that auto-captures research data and predefined models for computational analysis that do not require human intervention.

Combined with business best practices, including marketability and feasibility studies, these relatively simple changes have the power to bring life-changing therapeutics to market on timelines that make a difference.

RABI-767 proves that translational research can get drugs to market more quickly

In January 2021, a group of researchers from the Mayo Clinic published an article in Science Advances about a novel small molecule lipase inhibitor drug candidate to treat acute pancreatitis, a disease that under normal drug development timelines could kill up to 240,000 people before the therapeutic is approved for market. But this therapeutic is moving at an accelerated pace far beyond that of the traditional drug development pipeline. Licensed by Lamassu Pharma in early 2020, RABI-767 has already completed pre-clinical trials — a process that typically takes 3.5 years. The fast timeline resulted from the company prioritizing the acceleration of translational research and drug development due to a high confidence level in earlier data.

By considering the strict requirements for reproducibility and the business needs of a go-to-market strategy, at the time of study design, Lamassu Pharma reduced the timeline for pre-clinical trials from 3.5 years to less than a year. At the time of this article’s publication, RABI-767 is preparing for Phase 1 clinical trials; under typical drug development timelines, these trials would not begin until late-2024 at the earliest. That equates to 70,000 lives. RABI-767 cannot make it to market in time to save everyone who will suffer the effects of severe acute pancreatitis this year, but on an accelerated timeline, it has the potential to help hundreds of thousands of people in half the time.

Translational research is not rooted in the effort to accelerate drug development timelines. Rather this acceleration is a by-product of the goals and core mission of the field. The purpose of translational research is to bring academic research to market and transform ideas into actionable interventions. But at its core, translational research, especially in medicine, is about bridging the divide between academia and business to help save lives, not just one at a time, but by the thousands, and eventually by the millions. And it all starts with solving typically overlooked problems to increase reproducibility and get more viable therapeutics to market in time to help the most patients.

Dr. Gabi Hanna

Dr. Gabi Hanna

Dr. Gabi Hanna is the CEO and co-founder of Lamassu Pharma, a biopharmaceutical company focused on translational research or creating tangible outcomes from medical research. Hanna has worked for more than 15 years in small- and mid-sized biotech companies, focusing on planning, designing and executing early drug development studies. He co-founded one of the first academic units dedicated to advancing translational research through rigorous implementation of a comprehensive drug development program. Hanna is the chairman of the North Carolina Society of Physician Entrepreneurs, a board member of the Duke Institutional Review Board, and a board member and advisor for multiple companies, including Kaio therapy, Clickmedix and American Remote Health and Zoonco.