Today, we're going to be looking at rare diseases - something that people hear about, but don't really understand how common they are.
When you think about it, each rare disease on its own is uncommon. But there are so many rare diseases out there: over 7,000 known conditions. When you add up all the people who are afflicted, collectively, the impact is huge. In the US, it's estimated that about 30 million people are living with a rare disease- one in 10 Americans. That's a big number.
Many people with rare diseases go through what's often called a diagnostic odyssey. They may experience symptoms for years, visiting doctor after doctor, sometimes receiving multiple incorrect diagnoses before they finally get an accurate answer. In fact, there is an average wait time of 6.3 years for a diagnosis. That's a long time.
Patients endure frustration and uncertainty during all that time. It's hard to even imagine going that long. But what makes diagnosing these conditions so difficult?
One of the key factors is that the symptoms of many rare diseases can overlap with more common conditions. So it can be tricky for doctors to tease apart what's going on. Some providers have likened it to looking for a needle in a haystack. And even when a doctor suspects a rare disease, confirming that diagnosis can be challenging. It often requires specialized testing and expertise that may not be readily available in every medical setting.
Genetic testing is another important area. It's a key part of the process. Genetic testing can be a real game changer for diagnosing rare diseases. It helps identify the specific subtype of a rare disease, which is crucial for guiding treatment decisions. For example, limb girdle muscular dystrophy - or LGMD - is a group of over 30 different subtypes. All the subtypes cause muscle weakness and wasting. But knowing the exact subtype through genetic testing can be absolutely crucial for figuring out the right treatment approach.
We've got this huge diagnostic challenge, years of uncertainty before getting the right diagnosis. And then on top of that, most rare diseases don't even have approved treatments. It's a tough reality. It's estimated that 93% to 95% of the over 10,000 known rare diseases don't have any FDA approved treatments. And developing treatments for rare diseases is a long and costly journey.
One crucial question - how exactly does it help companies take on these challenging and often less profitable projects? An initiative called the Orphan Drug Act comes to mind.
The Orphan Drug Act (ODA) provides significant incentives for companies to develop these much needed treatments. For instance, it offers tax breaks, it waives certain FDA fees. The policy can even grant market exclusivity for a certain period of time. These incentives were designed to make it more financially viable for companies to invest in research and development for these rare diseases. Despite the hurdles, there are some companies out there making strides in this space.
The ODA, enacted in 1983, marked a pivotal moment in U.S. healthcare policy by addressing the challenges of developing drugs for rare diseases. These conditions, often overlooked due to their small patient populations, offer limited profit potential for pharmaceutical companies. The ODA introduced incentives to spur the creation of treatments for these underserved communities.
Under the law, the Orphan Drug Designation program enables the U.S. Food and Drug Administration (FDA) to grant special status to drugs intended to treat diseases affecting fewer than 200,000 Americans. Sponsors must also demonstrate that they are unlikely to recover development costs through domestic sales.
To encourage innovation, the ODA provides a suite of benefits for drug developers. These include tax credits for qualified clinical trials, the waiver of Prescription Drug User Fees, and seven years of market exclusivity for approved treatments. Additionally, the ODA established the Orphan Product Grants Program, which offers funding to support the development of drugs and medical products targeting rare diseases.
Despite its successes, the ODA faces calls for modernization. Proposed reforms include refining the definitions of rare diseases and orphan drugs, implementing patient assistance programs to enhance affordability, and creating systems to collect real-world data through patient registries. Stakeholders have also advocated for revisiting market exclusivity provisions to balance innovation with broader access to treatments.
Since its enactment, the ODA has facilitated the FDA approval of hundreds of orphan drugs, significantly expanding the options available to rare disease patients. However, with over 7,000 rare diseases identified, most still lack FDA-approved treatments, underscoring the urgent need for continued efforts.
The National Institutes of Health (NIH) has played a key role in complementing the ODA’s efforts through initiatives like the Therapeutics for Rare and Neglected Diseases (TRND) program, which accelerates the development of promising treatments. The NIH also established the Division of Rare Diseases Research Innovation (DRDRI) to focus on advancing research and the Genetic and Rare Diseases (GARD) Information Center to provide patients and families with reliable information.
At the FDA, the Office of Orphan Products Development oversees the ODA’s implementation, coordinates research funding, and serves as a vital resource for patients and advocacy groups. To further amplify awareness, the FDA hosts Rare Disease Day, an annual event fostering collaboration across the rare disease community.
The ODA and complementary government programs have significantly advanced the treatment landscape for rare diseases, but challenges remain. Legislative and research efforts must evolve to meet the needs of individuals living with these conditions, ensuring access to care and fostering hope for breakthroughs in even the most neglected areas of medicine.
This therapy is designed to deliver a crucial enzyme called GAA that's deficient in people with Pompe disease and helps stabilize it in the bloodstream. Pompe disease is a debilitating condition. It is a rare genetic disorder where the body can't produce enough of that GAA enzyme, an enzyme that is responsible for breaking down glycogen, which is a complex sugar that our bodies use for energy. Without enough GAA, glycogen builds up in cells, particularly in the muscles. This can lead to a whole range of problems.
The symptoms can vary depending on the severity of the disease. But they often involve progressive muscle weakness, breathing difficulties, and heart problems. In infants, Pompe disease can be especially severe, often leading to heart failure if it's not treated promptly.
Amicus's therapy is designed to address this enzyme deficiency by targeting the underlying cause of the disease. The research is promising, potentially slowing or even halting the progression of this debilitating condition.
John Crowley is the firm’s founder and chairman emeritus. He founded Amicus in 2005 to develop treatments for rare genetic diseases. His journey into biotechnology was driven by personal circumstances; in 1998, two of his children were diagnosed with Pompe disease, a severe neuromuscular disorder. This led Crowley to co-found Novazyme Pharmaceuticals, focusing on experimental treatments for the condition.
Under Crowley, Amicus advanced several treatments for rare diseases, including Galafold (migalastat) for Fabry disease, which received approval in Europe in 2016. He has served as the National Chairman of the Make-A-Wish Foundation of America and is a founding board member of the Global Genes Project. Crowley’s contributions have been recognized through various awards and honors. He and his family were the inspiration for the 2010 film “Extraordinary Measures,” which depicts their quest to find a cure for Pompe disease. Additionally, he is a Henry Crown Fellow at the Aspen Institute and has received honorary degrees for his work in biotechnology and patient advocacy.
Another company doing work in this space is Unicycive Therapeutics, led by founder and CEO Shalabh Gupta. Unicycive is focused on what they call underserved medical conditions, which captures a range of rare diseases.
Gupta and his team are taking a rather unique approach by targeting specific metabolic pathways. Their goal is to develop therapies that address the underlying causes of these diseases, rather than just managing the symptoms.
One area of particular interest to Gupta and his team at Unicycive is a focus on renal disease. They've developed a drug candidate that aims to slow the progression of chronic kidney disease by targeting a specific pathway involved in inflammation and fibrosis. Another area of their research is in the treatment of a rare metabolic disorder called acute intermittent porphyria (AIP), a rare genetic disorder that affects the way the body makes heme, a vital part of hemoglobin, which carries oxygen in the blood. In people with AIP, a problem with specific enzymes causes a buildup of substances called porphyrins and their precursors in the body. These buildups can lead to sudden and severe symptoms, often called “attacks.” AIP attacks can cause intense abdominal pain, nausea, vomiting, and constipation. Other symptoms may include confusion, muscle weakness, and even life-threatening complications like breathing problems. Stress, certain medications, alcohol, or hormonal changes can trigger these attacks.
Gupta is a physician who created Unicycive in 2016 to address unmet medical needs in renal diseases. Since that time, he has been on a mission to deliver transformative treatments for underserved patient populations. Gupta’s multifaceted career bridges medicine, business, and academia. As an attending physician at NYU Medical Center and a clinical faculty member at NYU School of Medicine, he honed his medical and teaching skills. Transitioning to the business world, he took on equity research roles at UBS Investment Bank and Rodman & Renshaw, analyzing pharmaceutical and biotechnology companies. He later served as a commercial strategist at Genentech. Gupta’s entrepreneurial spirit led him to found Biocycive Inc. and Globavir, where he collaborated with Stanford University to advance diagnostic technologies, forging partnerships with global diagnostic firms. Today, he advises prominent institutions like the UCSF Innovation Center and Stanford’s SPARK program, while contributing his expertise as a board member at UC Irvine’s Beall Center for Innovation and Entrepreneurship.
He earned his medical degree from India’s Jawaharlal Institute of Postgraduate Medical Education & Research and completed advanced training in internal medicine, physical medicine, and rehabilitation at NYU School of Medicine. He also holds a Master of Public Administration in Health Care Finance and Management from NYU’s Wagner Graduate School of Public Service. During his residency, he was elected president of the Resident Physicians Council, representing over 1,500 residents nationwide.
Sarepta Therapeutics is a biotech making significant strides in gene therapy for rare diseases, and particularly for limb girdle muscular dystrophy (LGMD). LGMD is a group of rare genetic disorders that cause muscle weakness and wasting, primarily in the muscles around the hips and shoulders. These muscles, known as the limb-girdle muscles, play a crucial role in movement, so people with LGMD may have trouble walking, climbing stairs, or lifting objects. Over time, the weakness can spread to other parts of the body, and in some cases, it may affect the heart or breathing muscles.
LGMD can be caused by changes (mutations) in specific genes that are responsible for making proteins that keep muscles strong and healthy. The condition is inherited, but the severity and age when symptoms start can vary widely depending on the specific type of LGMD. Although there is no cure yet, physical therapy, assistive devices, and careful monitoring of heart and lung health can help people manage the condition and maintain their quality of life. Scientists are also working on new treatments, like gene therapy, to target the underlying causes of LGMD.
Sarepta Therapeutics is led by President and CEO Douglas S. Ingram. Ingram has tried to apply genetic testing in identifying LGMD subtypes. Ingram has served as President and Chief Executive Officer of Sarepta Therapeutics since June 2017. Under his leadership, the company has expanded its portfolio to over 40 genetic medicine programs, including RNA, gene therapy, and gene editing candidates. Sarepta has also launched three RNA therapies and received approval for the first gene therapy to treat Duchenne muscular dystrophy (DMD). This growth has been accompanied by a compounded annual revenue increase of approximately 40%, transforming Sarepta into a profitable, cash flow-positive organization.
Before joining Sarepta, Ingram held several key positions in the pharmaceutical industry. He began his career at Allergan in 1996, eventually serving as President from 2013 until its acquisition by Actavis in 2015. Following his tenure at Allergan, he became President and CEO of Chase Pharmaceuticals, a clinical-stage biopharmaceutical company focused on neurodegenerative disorders, until its sale in 2016. Ingram holds a law degree, summa cum laude, from the University of Arizona and an undergraduate degree from Arizona State University.
Ingram’s tenure at Sarepta has been marked by significant milestones, including the recent U.S. Food and Drug Administration (FDA) approval of Elevidys, a gene therapy for DMD. This approval, which now includes patients aged four and above, has the potential to impact approximately 15,000 individuals in the United States. The company’s strategic partnerships, such as the recent $11.38 billion licensing agreement with Arrowhead Pharmaceuticals for gene-silencing products, further underscore Sarepta’s commitment to advancing treatments for neuromuscular diseases under Ingram’s leadership.
Sarepta is taking that a step further by using that genetic information to develop highly targeted gene therapies.
