Emil, whence the fascination with addressing unmet patient needs in rare diseases? Relatedly, what is the founding story of Ultragenyx?
My interest in treating previously untreatable diseases stems from my early exposure to medical breakthroughs, thanks to my father, a neurologist who treated Parkinson's patients with L-DOPA in the 70s. My career path was influenced during my time in medical school at UCLA in the 80s. This period was marked by significant advances in genetics, with new genetic diseases being discovered and gene therapies being developed. This shift led me to specialize in pediatrics and medical genetics. The inception of Ultragenyx ties back to my fellowship in 1991 when I worked on mucopolysaccharidosis type one (MPS1). My initial focus was academic, but it soon transformed into a deeply personal mission when I encountered patients directly affected by these diseases, particularly children with rare genetic conditions.
The challenge of bringing treatments to market for these rare diseases was stark. Despite developing effective treatments, I found that no companies were interested in marketing them due to the limited financial incentives. This realization was a pivotal moment, driving me to commit my career to overcoming this injustice. The journey involved considerable risk, including potential damage to my academic career, but the moral imperative to save lives outweighed these concerns. This resolve led to the establishment of Ultragenyx, focusing on developing treatments for rare diseases that were often overlooked by larger pharmaceutical companies.
How do you address the high cost of developing drugs for rare diseases? Is governmental involvement in this sector necessary, or can profitability be established?
Our approach at Ultragenyx has been to streamline the drug development process, making it faster and more cost-efficient. This optimization involves designing studies that allow us to make scientific leaps, thereby reducing the development time from the typical 10-12 years to just 3-5 years.
However, the nature of rare diseases means that the drugs developed are inevitably expensive. This raises the question of accessibility, which is a crucial part of our mission. We ensure that patients, regardless of their financial situation, have access to these treatments in the U.S. This commitment extends to our UltraCare program, which supports patients in accessing medication, covering copays, and, when necessary, providing drugs for free.
While the free market plays a significant role in drug development, the pricing of these drugs necessitates careful balance. Ultragenyx focuses on making treatments accessible while maintaining a viable business model. The role of the government, in my view, is not directly in drug development but in fostering a regulatory environment that accelerates the approval process and supports the efficiency of drug development. This can be achieved by improving the qualification of biomarkers for rare diseases, enabling quicker and more efficient clinical trials. This approach not only addresses the financial aspects but also significantly reduces the burden on patients and society.
It is stated on your website that 17 of the 18 diseases you are targeting lack an approved therapy. Why is that?
The primary reasons for the lack of approved therapies for these diseases are their rarity and the complexity of the diseases themselves. For instance, some diseases like Sanfilippo syndrome presented unique challenges due to the inability of treatments to reach targeted areas like the brain. However, advances in AAV gene therapy have opened new possibilities for treatment. Despite these technological advancements, the rarity of these diseases poses significant commercial challenges. For example, Sanfilippo syndrome affects only about 40 patients a year in the U.S., making the financial investment in developing treatments daunting.
Our focus now is on using biomarkers to measure disease levels in the brain and to seek approval for treatments based on smaller patient groups. This strategy could align the cost of development with potential returns. However, the requirement for extensive clinical trials can lead to the termination of many programs. The challenge lies in balancing the need for rigorous testing with ethical and financial realities.
In the broader context, it is startling to note that 95% of rare diseases have no treatments. My work in this field is driven by the gratification of using cutting-edge technology to transform the lives of patients suffering from these severe and devastating diseases. Our goal is to effectively channel financial resources into developing treatments for these rare diseases. Once approved, these treatments have a lasting impact, as exemplified by the 20-year success of a treatment developed in my early research.
Can you tell us about your FDA-approved drugs, as well as the promising treatments in your pipeline?
We have made significant strides with FDA-approved drugs like Vestronidase alfa for MPS7, approved based on a trial with just 12 patients, and Crisvita for X-linked hypophosphatemia (XLH). Vestronidase alfa, despite being for a very rare disease, was approved rapidly, showcasing the efficiency of our development process. Crisvita treats a larger patient population and addresses bone deformities in children by normalizing phosphate levels. These approvals demonstrate our ability to rapidly develop and bring to market treatments for rare diseases.
Looking ahead, we are excited about potential treatments for osteogenesis imperfecta (OI) and Angelman syndrome. In OI, we have developed an antibody that appears to significantly reduce fractures and improve bone strength in clinical studies. We recently presented data demonstrating a significant reduction in fracture rate, which has resulted in some patients in our study moving from wheelchairs to walking unaided. For Angelman syndrome, a developmental brain disorder, we are using antisense oligonucleotides to activate specific genes, resulting in promising improvements in cognition, communication, and motor skills in affected children. These investigational treatments, made possible by recent technological advancements, hold the promise of addressing diseases once deemed untreatable.
Your new manufacturing facility in Massachusetts is said to be one of the first in the U.S. with complete end-to-end gene therapy capabilities. Why is this significant?
Our Bedford facility represents a significant advancement in gene therapy manufacturing. It is equipped to handle both traditional HEK manufacturing and our innovative Pinnacle PCL platform, enabling us to produce a wide range of gene therapies. This facility’s unique ability to run multiple production cycles annually increases our capacity to develop treatments for both common and ultra-rare diseases. Moreover, the efficiencies we have achieved in the manufacturing process are crucial in reducing the cost of gene therapies, which are typically very expensive. This reduction in cost is vital for making these therapies more accessible worldwide, especially in developing countries where such treatments can be life-changing. Our goal is to set a new standard in gene therapy, making these advanced treatments more widely available for diseases that have no other treatment options.
