FDA approves drug developed through SPARK
Posted on November 25th, 2024
A Triumph for Academic Drug Discovery: FDA Approves Attruby for Life-Threatening Heart Disease
Stanford, CA – In a groundbreaking achievement highlighting the transformative power of academic innovation in driving drug discovery from “bench to bedside”, SPARK at Stanford proudly announces the FDA approval of a therapy using a technology developed at Stanford SPARK and licensed by Eidos from Stanford University. The therapy is AttrubyTM (Acoramidis) for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), a progressive and life-threatening heart condition with limited therapeutic options.
Attruby (Acoramidis) was originally developed by Dr. Isabella A. Graef, MD, former faculty member at Stanford University, CEO of Shenandoah Therapeutics, and industry advisor to SPARK at Stanford; and Dr. Mamoun M. Alhamadsheh, PhD, Professor of Pharmaceutical Chemistry at the University of the Pacific. Previously known as the Alhamadsheh-Graef molecule 10 (AG10), Attruby (Acoramidis) received FDA marketing approval for the treatment of ATTR-CM. Attruby (Acoramidis), unchanged from its original academic discovery, transitioned seamlessly into clinical trials without further medicinal chemistry optimization, marking a rare and significant achievement as it was adopted directly by Eidos Therapeutics in 2013 and BridgeBio Pharma, Inc in 2021. The FDA approval of Attruby is a testament to the transformative power of rigorous science and team effort within university laboratories.
Attruby (Acoramidis) is the result of an interdisciplinary collaboration between Dr. Graef, a physician-scientist, and Dr. Alhamadsheh, a medicinal chemist. The drug is designed to stabilize the transthyretin (TTR) protein in patients with ATTR-CM by mimicking the protective effects of the rare T119M mutation. This mechanism halts the amyloid deposits that cause cardiac damage. Clinical trials have demonstrated the drug’s exceptional efficacy, improving both survival rates and quality of life, offering renewed hope to thousands of patients worldwide.
This breakthrough began when the research team had the insight that achieving complete stabilization of both normal and mutant TTR required a molecule with a novel binding mechanism—one that unlike existing other stabilizers also interacts with the bottom of the T4 binding pocket of TTR, and fits like a hand in a glove into this pocket. At Stanford, the team conducted the first high-throughput screen for TTR ligands, uncovering novel and structurally diverse compounds. Using structural insights from the co-crystal structures of these ligands with TTR, Dr. Alhamadsheh designed and synthesized AG10/Acoramidis, a compound that fits the binding pocket with remarkable precision. Its superior potency over other TTR stabilizers was demonstrated through collaborations involving Scripps Research Institute, Stanford University, and the University of the Pacific.
In 2012, Dr. Graef and Dr. Alhamadsheh became part of the SPARK at Stanford program to develop AG10/Acoramidis into a clinical candidate. Dr. Graef’s leadership in overseeing biological studies and securing initial funding played a crucial role in advancing the discovery toward clinical therapy.
Dr. Ron Witteles and Dr. Michaela Liedtke, both esteemed faculty members at Stanford University, played key roles as clinical collaborators during the early research on AG10.
The drug’s development journey culminated when Dr. Alhamadsheh and Dr. Graef co-founded Eidos Therapeutics in 2013. Eidos’ public offering in 2018 accelerated Acoramidis’ progress, while the 2021 merger with BridgeBio Pharma ensured the successful completion of clinical trials, establishing the drug as a “best-in-class” therapy for ATTR-CM. This FDA approval marks a monumental milestone, delivering a life-changing solution to patients suffering from this devastating disease.
Dr. Graef commented, “This success is the result of years of dedication, collaboration, and a shared commitment to improving patients’ lives. I am truly grateful that Dr. Alhamadsheh and I have been able to contribute to a therapy that can make a meaningful difference for those affected. We both hope this achievement inspires the scientific community, particularly young scientists, by showing what can be accomplished through perseverance and teamwork. It demonstrates the importance of sustained effort and commitment in tackling complex challenges. We are also grateful for SPARK’s mentoring and guidance, which was so important for us in developing AG10/Acoramidis.”
The FDA approval of Attruby is a testament to the success of the transformational SPARK at Stanford program and its unique model of combining innovative education and training with multidisciplinary mentoring and support from volunteer industry experts.
SPARK at Stanford was founded in 2006 to address the challenges associated with translating academic ideas and findings to benefit patients. Many innovative solutions discovered in academia never make it to patients due to a disconnect between academia and industry. Each year, SPARK selects about 12 promising academic projects to receive funding along with close mentoring from experts in industry to provide the knowledge and infrastructure to get academic discoveries across the “valley of death” to clinical trials and commercialization.
To honor the clinical trial participants who contributed to the clinical success of Attruby, BridgeBio will offer the treatment to these patients free for life.
Attruby could capture a significant share of the more than $10 billion ATTR-CM market, with peak sales conservatively estimated at around $3 billion, and its approval represents a transformative moment in the treatment of transthyretin amyloid cardiomyopathy. Beyond its clinical significance, it highlights the immense impact of academic-industry partnerships in driving medical innovation.
Read more from BridgeBio here.
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