Rarecast

The ability to target the underlying cause of a disease and make a lasting correction makes gene therapy an attractive approach to treating neurodegenerative conditions. The advent of Zolgensma, a gene therapy for the treatment of the rare neurodegenerative condition spinal muscular atrophy, serves as a model for this approach. A recent review article in Nature Neuroscience looks at the advances in development of gene therapies for neurodegenerative disease and considers the challenges and promises. We spoke to article co-author Subhojit Roy, professor in the departments of Pathology and Neuroscience at the University of California, San Diego, about the pace of activity in this area, why he believes it is so promising, and its potential extend beyond monogenic diseases. This podcast is part of our ongoing Platforms of Hope series that explore advances in gene Thanks to Pfizer, Inc., Bluebird, and Novartis Gene Therapies for their support of this podcast article, part of our Platforms of Hope: Advances in Gene

Poseida Therapeutics is perhaps best known for its immune-oncology cell therapy products, but the company’s platform technologies are also being used to develop a growing pipeline of gene therapy candidates. While the most advanced ones in its pipeline use viral vectors, newer candidates make use of a non-viral nanoparticle vector. This technology can increase the payload of the gene therapy, avoid issues of immunogenicity, allow for redosing, and deliver manufacturing advantages. We spoke to Eric Ostertag, CEO of Poseida, about the company’s platform technology, its gene therapy pipeline, and its efforts to move beyond viral vectors. Thanks to Pfizer, Inc., Bluebird, and Novartis Gene Therapies for their support of this podcast, part of our Platforms of Hope: Advances in Gene Therapy and Gene Editing series.

Jazz Pharmaceuticals has been successful at building and commercializing a growing pipeline of therapies to treat rare neurologic conditions and hematologic cancers. Central to its strategy has been the use of acquisitions to build its pipeline. In fact, we should note that since recording this podcast, the company continued that approach with news that it would acquire GW Pharmaceuticals for $7.2 billion to expand its neuroscience portfolio. We spoke to Robert Iannone, executive vice president of research and development and chief medical officer of Jazz about the company’s neuroscience pipeline, its growing family of commercial products, and how its preparing to maintain its leadership in the treatment of the rare sleep disorder narcolepsy as new competitors move toward market.

CRISPR is a powerful editing tool, but it works best as a way to knock out genes rather than correct them. New approaches to gene editing, though, are providing the promise of more effective tools for addressing the underlying drivers of monogenic diseases. A recent study in Nature of an approach known as base editing in a mouse model of the ultra-rare genetic condition progeria, a disease that causes premature aging, demonstrated the powerful potential of the approach. While CRISPR has been likened to scissors, base editing has been compared to the find-and-replace function of a word processor. We spoke to study leader David Liu, director of the Merkin Institute for Transformative Technologies at the Broad Institute, about base editing, how it works, and why it may offer the potential to treat a wide range of rare diseases. This episode is part of an occasional series on innovations in gene editing and gene therapy.

Arya Singh grew up with a child’s-eye-view of hospitals, operating rooms, and clinical trial sites. As someone with the rare and progressive neuromuscular disorder spinal muscular atrophy type 2, Singh knew what it meant to be isolated and frightened by both as a patient and a clinical trial participant. Now a student at Yale University with plans to pursue her interests in law and public policy in health, she has written Courageous Calla and the Clinical Trial. We spoke to Singh about the surgeries and clinical trials she endured as a child, her new book Courageous Calla, and her interest in humanizing medicine.

Glioblastoma is an aggressive and rare brain cancer. Though it is typically treated with surgery, radiation, and chemotherapy, the prognosis for patients is grim with only 10 percent of surviving at least five years. Plus Therapeutics is developing a pipeline of radiotherapies that are encapsulated in nanoliposomes. Through novel deliver and formulation of these therapies, the company believes it can produce safer and more efficacious treatments. We spoke to Marc Hedrick, CEO of Plus Therapeutics, about the company’s nanoliposome technology, how it works, and why the company is focusing on rare cancers. 

Patients’ data is critical to rare disease innovation, but it does little to help advance progress if it is not widely accessible to researcher. RARE-X is a nonprofit working to bust data silos through a federated data-sharing platform and empower rare disease patient communities to more easily gather, structure and securely share critical data through a common platform. We spoke to Nicole Boice, co-founder and executive director of RARE-X, about the problem RARE-X is seeking to address, the technology and expertise the organization has been able to bring together, and why data sharing is essential to accelerating the diagnosis or rare diseases and development of new treatments to treat them.

The genetic basis of sickle cell disease has been long understood, but it has only been recent that new treatments and a growing pipeline of therapies have emerged. The inherited blood disorder causes red blood cells to become crescent shaped, which restricts the flow in blood vessels and limits oxygen delivery to the body’s tissues leading to severe pain and organ damage. At the end of 2019, Global Blood Therapeutics won accelerated approval for Oxbryta, the first FDA-approved therapy that directly inhibits sickle hemoglobin polymerization, the root cause of sickle cell disease. We spoke to Ted Love, president and CEO of Global Blood Therapeutics, about the changing landscape of sickle cell disease, Oxbryta and the company’s pipeline behind it, and how the company is approaching the global need for the drug given the higher prevalence of the disease in parts of the world.

At the end of November, the U.S. Food and Drug Administration approved Rhythm Pharmaceuticals Imcivree, the first therapy for chronic weight management in patients with certain genetic forms of obesity. The approval validates Rhythm’s approach to target a specific biological pathway common to a number of these conditions. We spoke David Meeker, CEO of Rhythm, about genetic obesities, the company’s drug Imcivree, and his plans to expand its use beyond the initial approved indications.

Orchard Therapeutics founder and former chief scientific officer Bobby Gaspar took the helm of the gene therapy company in March to replace CEO Mark Rothera when he stepped down. Since taking over, Gaspar has led a restructuring of the company and narrowed the focus to prioritize what it saw as high-value programs including its gene therapy for metachromatic leukodystrophy, a rare and life-threatening inherited disease of the body’s metabolic system. We spoke to Gaspar about the company’s sharpened focus, its gene therapy in development for metachromatic leukodystrophy, and where he sees the greatest opportunities for Orchard going forward.

Tessera Therapeutics is seeking to move beyond gene editing and gene therapy to what it calls “gene writing.” The company said its technology can be used to change base pairs, make small insertions or deletions, and integrate entire genes into the genome. We spoke to Geoffrey von Maltzahn, co-founder and CEO of Tessera, about the company’s gene writing technology, how it works, and the potential for it to accelerate the pace of genetic medicine.

In November, the U.S Food and Drug Administration approved Eiger Biopharmaceutical’s Zokinvy, the first therapy to treat the ultra-rare disorder progeria, a genetic disease that causes premature aging. The approval of Zokinvy, which began life as a potential cancer therapy known as lonafarnib, shows the essential role patient organization can play in driving research and bringing together collaborators to advance the understanding of a condition and develop treatments. We spoke to Leslie Gordon, co-founder and medical director of the Progeria Research Foundation, about the role the organization has played in creating an understanding of progeria, identifying and advancing a therapy for the condition, and how a windfall from the sale of a priority review voucher from the approval of the therapy will help advance future research.

The rare disease drug developer Retrophin has been through a number of changes in recent years including a new CEO, a late-stage failure of a key program, and the resolution of dueling lawsuits between it and its former CEO and convicted fraudster Martin Shkreli. Now with data from its lead experimental therapy sparsentan expected next year in two different rare kidney diseases, the company has changed its name to Travere Therapeutics. We spoke to Eric Dube, CEO of Travere, about the company’s new identity, its experimental therapy sparsentan, and the rare kidney diseases it is being developed to treat. 

While gene therapies provide great promise for people with rare, genetic diseases, the pursuit of these one-time treatments may not seem economically viable to commercial developers. In the case of ultra-rare conditions, the patient populations may be so small that it may not be possible for companies to recoup their investments, let alone make a profit. The nonprofit Columbus Children’s Foundation is providing funding and scientific resources to accelerate access to gene therapies for children with ultra-rare genetic disorders. We spoke to Jude Samulski, a gene therapy innovator and chairman and chief scientific officer of the Columbus Children’s Foundation, about the foundation operates, the range of capabilities it is able to bring together, and the potential to scale what it does to reach more patients in need of treatments.

Daniel de Boer became a biotech executive after his son was diagnosed with the genetic respiratory disease cystic fibrosis. He founded ProQR Therapeutics with an initial focus on developing RNA therapies to treat cystic fibrosis, but the company has since turned its attention to a group of rare, inherited retinal diseases that cause blindness. We spoke to de Boer, CEO of ProQR, about the evolution of ProQR, its pipeline of antisense oligonucleotide therapies, and the advantage of this approach in treating rare eye diseases.

The economics of developing gene therapies can make it unattractive for biopharmaceutical companies to invest in bringing a gene therapy through development and to the market for ultra-rare conditions. But researchers at the National Center for Advancing Translational Sciences are working to develop a set of gene therapy vectors that can be used in multiple indications and eliminate the time and cost of preclinical development for a range of conditions through its Platform Vector Gene Therapy, or PaVe-GT program. In this fourth and final part of our gene therapy series, we spoke to P.J. Brooks, program director in the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences, about the PaVe-GT program, the potential for developing a toolkit of plug-and-play vectors, and how this can alter the cost of developing gene therapies for ultra-rare and individual patients. This series is made possible through support from BioMarin, Pfizer, Retrophin, Novartis Gen

Though there are only a handful of gene therapies on the market today, there is a robust and growing pipeline of these transformative medicines advancing toward market. In this third part of our gene therapy series we spoke to Janet Lambert, CEO of the Alliance for Regenerative Medicine, about the state of the gene therapy industry, the challenges developers face in advancing therapies to the market, and emerging pricing approaches to make them accessible to the patients who need them. This series is made possible through support from BioMarin, Pfizer, Retrophin, Novartis Gene Therapies (formerly AveXis), UCB Inc., Genentech, Ultragenyx, Novartis, RegenxBIO, and Sangamo Therapeutics.

Shortly after birth, Kim Nye’s first daughter Tessa began suffering seizures. Though Nye gave birth to other children without significant health issues, when her fourth child Colton was born, he had the same symptoms as his oldest sister. The two siblings were eventually diagnosed with an ultra-rare genetic disorder and Nye began the TESS Research Foundation. The organization has been pursuing a gene therapy, which a biopharmaceutical company is now working to develop. In this second part of our series on gene therapies, we spoke to Nye about her own journey to becoming a rare disease advocate, how a gene therapy fit into her organization’s research agenda, and the considerations she is weighing before dosing her children with an experimental gene therapy.

Genetic counselors play a unique role in the medical life of a person with a rare disease. They can serve as guide, translator, and trusted advisor. In this first part of our four part series on gene therapies, we spoke to genetic counselor Stephanie Gandomi, a Global Genes advocacy resource, about gene therapies, the role genetic counselors play in working with rare disease patients, and the considerations rare disease patients may make about whether to pursue a gene therapy through a clinical trial. This series is made possible through support from BioMarin, Pfizer, Retrophin, Novartis Gene Therapies (formerly AveXis), UCB Inc., Genentech, Ultragenyx, Novartis, RegenxBIO, and Sangamo Therapeutics.

Nell Meosky Luo remembers the way her mother use to keep extensive journals documenting the symptoms and treatments of her brother, who has a rare immune disorder. It served as inspiration for Folia Health, which has developed a platform that allows patients and caregivers to maintain health records, manage their conditions, and communicate with their physicians. We spoke to Luo, founder and CEO of Folia Health, about how patients are using the platform, its potential to gather real-world data, and how the data it gathers could be used to advance the understanding of rare diseases.