Rarecast

Partnering is essential to advancing rare disease therapies, but while researchers, drugmakers, and patient groups share a common desire to bring new treatments to market, differences in how they operate, their culture, and priorities can derail progress. We spoke to Karen Erickson, associate executive director of community engagement at the Alpha-1 Foundation, about the elements of successful partnering, how to align the differing interests of the participants, and how to get everyone to work together to achieve common goals.

Art Pappas, a former pharmaceutical executive turned venture capitalist, has spent more than 30 years working for and investing in drug companies. Among the areas he focuses on are rare disease drug developers. We spoke to Pappas about the changing climate for investment in rare disease companies, his thought process in evaluating potential investments, and at what point he considers exit strategies.

Patient organizations have long been working with biopharmaceutical companies, but as they have grown more sophisticated about their interactions, they are coming to understand the value in laying out the ground rules for these relationships. Last year, the International Fibrodysplasia Ossificans Progressiva Association, or IFOPA, took the unusual step to craft a set of guidelines for the organization regarding how it engages with the pharmaceutical industry. It made these guidelines public and continues to refine them. We spoke to Betsy Bogard, chair of the IFOPA research committee, about why the organization created the guidelines, how they have affected interactions between the organization and industry, and how other organizations are interested in following suit.

To bring new therapies to market to treat rare diseases requires more than scientific innovation. Innovation in financing and business models can be critical as well as the need to find ways to cost effectively develop new medicines becomes increasingly important. We spoke to Neil Kumar, CEO of BridgeBio, about his company’s strategy for developing a portfolio of rare disease therapeutics, why the company’s not alone in this effort, and what he’s learned so far through this approach.

A group of twentysomethings backpacking their way through Europe may not sound unusual, but for Kevan Chandler and his friends, their trip in 2016 was by no means a typical backpacking adventure. Chandler, born with the rare neuromuscular condition spinal muscular atrophy, has been wheelchair bound for most of his life. Because the planned trip included several places that were not wheelchair accessible, the friends decided to rig a backpack to carry Chandler and leave the wheelchair at home. We spoke to Chandler about the journey, how it led to the creation of the nonprofit We Carry Kevan, and why he is working to change the way people think about accessibility and dependency.

Simon Wheatcroft lost his ability to see at the age of 17, the result of a rare genetic disorder. After becoming blind, though, Wheatcroft developed a penchant for running. Starting on a soccer field where he ran between goal posts, he graduated to public roadways. Since those early outings where he had sometime painful encounters road signs and other obstacles, Wheatcroft has learned to adapt, use technology and his other senses, and become an ultramarathoner. We spoke to Wheatcroft about the loss of his sight, how he has been able to adapt, and what he’s learned about himself in the process.

Last month, Spark Therapeutics submitted its gene therapy Luxturna, an experimental treatment for a rare inherited disease that causes blindness, to regulators in the United States and Europe. The company also won U.S. Food and Drug Administration designation for the experimental therapy as a treatment for a rare pediatric disease. Luxturna could be the first treatment for inherited retinal disease and the first gene therapy for a genetic disease approved in the United States. We spoke to Paulo Falabella, medical affairs ophthalmic lead for Spark Therapeutics, about Luxturna, what clinical trials to date tell us, and why this represents a significant development for not just Spark, but the entire field of gene therapy.

Fulcrum Therapeutics is working to develop small molecule drugs to modulate gene activity as a way to treat certain rare diseases. The company, established by the venture capital firm Third Rock Ventures, is initially focusing on Fragile X and a form of muscular dystrophy known as FSHD. We spoke to Walt Kowtoniuk, director of strategy and operations for Fulcrum, about its approach, what he learned working in a venture capital firm, and what advice he would offer rare disease patients turned investors.

When BioMarin failed to win U.S. Food and Drug Administration approval for its experimental Duchenne muscular dystrophy drug drisapersen, it decided to its cease development. Though there were concerns about both the safety and efficacy of the drug, there were patients who participated in the clinical trials who felt that they benefitted from it. CureDuchenne established CD Access, a new nonprofit that negotiated a novel agreement with BioMarin to get control of the existing supply of drisapersen, which the nonprofit is distributing to patients in Canada who participated in the clinical trials. We spoke to Debra Miller, CEO and founder of CureDuchenne and CD Access, about the program, how it works, and whether it serves as a model for getting other similar drugs to patients in the future.

The diagnostic odyssey rare disease patient face can be long and daunting. Centogene is trying to help these patients find answer more quickly through its genetic diagnostics. The company has been focused on getting beyond the noise generated by the rapid increase in the volume of data to get accurate understanding of a patient’s genetics and helping doctors obtain actionable information. Strengthened with a recent $28 million financing, the company is expanding its presence in the United States. We spoke to Arndt Rolfs, CEO of Centogene, about the company’s genetic diagnostic services, its expansion plans, and the competitive advantage it believes it holds in its proprietary data.

PFIC is a rare genetic disorder that causes progressive, life-threatening liver disease. In many cases, PFIC leads to cirrhosis and liver failure within the first 10 years of life. Albireo, a 2008 spin-out of AstraZeneca, is developing bile acid modulators to treat PFIC and other rare pediatric liver diseases and gastrointestinal disorders. We spoke to Ron Cooper, CEO of Albireo, about PFIC, the challenge of developing a therapy for a disease with multiple forms and causes, and the path forward for the company.

aTyr Pharma is exploring a new set of naturally occurring proteins within the body dubbed physiocrines that modulate biologic activity and may provide therapeutic benefit. The company is pursuing this new class of molecules to treat a number of rare diseases. The company’s lead drug candidate Resolaris is being developed to treat FSHD, a rare genetic myopathy in which immune cells invade diseased skeletal muscle and cause muscles to grow weak and deteriorate. We spoke to John Mendlein, CEO of Atyr Pharma, about physicorines, how they can restore homeostasis to the immune and other systems, and why these molecules might be harnessed to treat a range of diseases.

Duchenne Muscular Dystrophy, a rare genetic disease, causes progressive muscle wasting that slowly robs people of abilities and leads to death. In recent years, much attention has focused on the use of antisense oligonucleotides to bypass defective portions of the exon that codes for the dystrophin gene to restore its production. Dystrophin is a protein that is essential to healthy muscle. Summit Therapeutics is taking a different approach. Instead of restoring dystrophin, Summit is developing a drug that activate utrophin, a related protein that serves a similar function to dystrophin during fetal development, but then shuts off. We spoke to Glyn Edwards, CEO of Summit, about the company’s utrophin activator ezutromid, its licensing deal with Sarepta Therapeutics, and why, unlike the exon-skipping drugs that target specific subpopulaitons of Duchenne patients, ezutromid could provide benefits to patients broadly.

Enzyme replacement therapies are available for a number rare, metabolic diseases that collectively are known as lysosomal storage disorders. These therapies have brought great benefits to patients. One problem, though, is that the enzymes don’t cross the blood-brain barrier and don’t address the severe and progressive neurological complications caused by many of these diseases. ArmaGen thinks it has a solution. By connecting the enzyme to a protein that is allowed to cross the blood-brain barrier, ArmaGen hopes to exploit a natural mechanism to address the CNS complications of these diseases. We spoke to Mathias Schmidt, CEO of ArmaGen, about the company’s platform technology, its pipeline of enzyme replacement therapies for lysosomal storage disorders, and its implications for more common neurological diseases.

The promise of gene editing and gene therapy has rare disease patients not only contemplating the potential of new treatments, but ones that can free them from chronic therapies and potentially provide cures. Sangamo Therapeutics, long pursuing its proprietary gene editing technology, is suddenly moving into the clinic with four experimental therapies including a a gene therapy for hemophilia A, and gene editing therapies for hemophilia B, MPS I, and MPS II. The company is currently enrolling three trials and expects to begin enrollment on a fourth trial later this month. We spoke to Sandy Macrae, president and CEO of Sangamo, about the diseases it is targeting, the company’s unique approach to gene editing, and it strategy for moving its therapies through clinical development and to the market.

Clinical trials for rare disease therapies face many challenges due to the small patient population on which they draw, the fact that often there may be many unanswered questions about a specific disease, and the potential variation in the way a rare disease manifests itself in patients. We spoke to John Boland, vice president of product development for the Atlantic Research Group, about the contract research organization’s recent white paper on “Critical Considerations for Rare and Orphan Disease Trial Planning” (http://bit.ly/2qE2qpb), the special challenges of conducting rare disease clinical trials, and how to best address these unique challenges.

For many rare disease patients, the drug discovery and development process moves slower than the diseases they are battling. Earlier this month, representatives of the patient community joined with academic researchers and drug developers at the Charles River Rare Disease Symposium in Cambridge, Massachusetts to explore way to accelerate the process of drug discovery and move more quickly toward human clinical trials. We spoke to Doug Macdonald, director of research operations and scientific alliances for CHDI Management and Antti Nurmi, managing director of Charles River Discovery Services, about the obstacles to rare disease drug discovery, the critical role collaborations play, and what can be done to accelerate the process.

Last month the U.S. Food and Drug Administration granted Enzyvant both Breakthrough Therapy Designation and the newly established Regenerative Medicine Advanced Therapy Designation for its investigational cell therapy to treat complete DiGeorge Syndrome, a rare and fatal disease. Enzyvant is the first company to win both designations and only the second to win the Regenerative Medicine Advanced Therapy Designation established through the 21st Century Cures Act. The designations provide for accelerated review pathways and special access to developmental guidance from the FDA. We spoke to Alvin Shih, CEO of Enzyvant and Louise Markert, the Duke University immunologist who has been pioneering the therapy, about Complete DiGeorge Syndrome, the innovative approach they are using to treat it, and the path forward for the therapy. As a matter of disclosure, Shih is co-chair of Global Genes Medical and Scientific Advisory Board.

There is increasing recognition of the important role patients can play by providing their insights into the drug discovery and development process. The Penn Medicine Orphan Disease Center and Global Genes will be hosting the second annual Rare Patient Advocacy Symposium in Philadelphia May 19, at the Sheraton University City Hotel, a day-long exploration of how rare disease patients can better get their voices heard in this process. We spoke to David Fajgenbaum, associate director of patient impact for the Penn Medicine Orphan Disease Center and research assistant professor of Medicine at the Perelman School of Medicine, about the changing view of rare disease patients, their emerging role in the drug development process, and the value they can provide to researchers, regulators, and drug developers.

Porphyria is a rare and intensely painful blood disease. Because it can manifest itself with symptoms similar to those caused by far more common disorders, it can be difficult to diagnose. Colin McEwen went through an 18-year diagnostic odyssey, in part because injuries he suffered as a child from an auto accident obscured from doctors the actual cause of his maladies. His problems were made that much more difficult as his search for relief from the pain from his disease led doctors to dismiss him as a drug-seeker. We spoke to McEwen about porphyria, the experiences he went through to get to a diagnosis, and how having a diagnosis has changed his ability to manage the disease.