Rarecast

Moving a rare disease therapy from the lab to the marketplace requires patients willing to participate in clinical trials that can demonstrate its safety and efficacy. But given the small number of people who may have a specific rare disease, finding these patients can slow the development of new therapies and create a barrier to getting treatments to patients who need them. We spoke to Sandra Shpilberg, CEO of Seeker Health, about the challenges drug companies face finding patients for rare disease drug trials, her firm’s efforts to combat that with its RarePatient database, and how the use of social media is changing the way drug developers connect with rare disease patients.

Patients with a rare disease may face debilitating, degenerative, and even life-threatening conditions, often with little treatment options. Their willingness to accept risks in the use of a therapeutic that may provide them benefit may lead to a different calculus than what regulators might consider. A study published at the end of May in the Orphanet Journal of Rare Diseases sheds light on how rare disease patients might weigh the potential benefits and risks of a therapy. We spoke to Thomas Morel, lead author of the study and a research fellow at Leuven University in Belgium, about his findings, what factors change a patient’s willingness to assume risks, and how this work might advance the discussion about the need to better consider patients’ perspectives in the regulatory process.

Gene therapy is offering rare disease patients the promise of delivering potential cures, but as it is generally approached today it has technical challenges to overcome, manufacturing complexities, and an expected high cost. Homology Medicines is taking a unique approach to gene therapy that makes use of a special set of viral vectors that gets around many of the obstacles other gene therapies face. We spoke to Arthur Tzianabos, CEO of Homology Medicines, about the company’s gene therapy, how it’s unique, and why its production and cost may be similar to other biologics today.

Orchard Therapeutics, a London-based gene therapy company with facilities in the United States, unveiled itself in May with $30 million in funding. The company is developing gene therapies to treat rare diseases involving metabolic disorders and immune deficiencies. Orchard uses a patient's own Hematopoietic stem cells, which are modified with a functioning copy of the missing or faulty gene, before being transplanted back into the patient's body. We spoke to Andrea Spezzi, chief medical officer for Orchard about the company, its approach to gene therapy, and how its addressing the challenges of bringing such treatments to market.

Mitochondria, the powerhouses of the cell, play a critical role in a range of rare and common diseases. Retrotope, a development-stage company, thinks it’s found a way to repair the damage done by various disease processes to mitochondira. The company is just concluding an early-stage trial of its experimental therapy to treat the rare disease Freidreich’s ataxia. We spoke to Bob Molinari, CEO of Retrotope, and Harry Saal, chairman of the company, about mitochondrial diseases, the approach the company is taking, and why its work may have broad implications for a wide range of degenerative diseases.

Howard Jacob understands the value of whole genome sequencing as a diagnostic tool. Jacob and his team were the first to use the technology to diagnose a child with an ultra-rare disease, which allowed doctors to save the boy’s life. Jacob, now chief medical genomics officer of HudsonAlpha Institute for Biotechnology, is working to use whole genome sequencing to find answers for other undiagnosed patients and expand the technology’s use as a clinical tool. We spoke to Jacob about the use of whole genome sequencing in the clinic, how it’s changing the way patients with rare diseases are treated, and the value of a diagnosis even in the absence of an available treatment.

Clinical trials for rare disease therapies can pose some unusual logistical challenges that can make it difficult to get patients to participate or remain enrolled in the trial until its completion. Clincierge provides a service that aim to reduce barriers to trial participation. It arranges travel and housing logistics, provides payment and reimbursement systems to address out-of-pocket expenses for patients, and supports family and caregivers to address a patient’s special needs. We spoke to Scott Gray, CEO of Clinicierge, about the challenges drug developers face in rare disease trials, what Clinicierge does to address them, and how its service reflects the growing trend toward patient-centricity.

Obsessive compulsive disorder, tics, anxiety, attention deficit hyperactivity disorder, and behaviors associated with autism spectrum disorders can be caused by a treatable autoimmune condition that is triggered by common infections. These conditions, known as PANDAS and PANS can often be misdiagnosed and wrongly treated to the detriment of the children with the condition. We spoke to Craig Shimasaki, CEO of Moleculera Labs, which has developed a diagnostic to determine if an individual’s neurologic or psychiatric symptoms could be caused by an autoimmune dysfunction. Shimasaki discussed these conditions, what we know about them, and how the availability of a diagnostic is helping change the way these patients are understood and treated.

Researchers seeking information about genes and genetic variants face the challenge of needing to search multiple databases, each with their own unique set of formatting issues. To unlock the information they are seeking, they often must spend hours wading through databases, restructuring data, and addressing nonstandard annotations. A groups of scientists at The Scripps Research Institute is addressing that problem through the development of two web services—MyGene.info and MyVariant.info—that pull data from multiple databases and provide a uniform structure for the information. We spoke to Chunlei Wu, associate professor of molecular medicine at Scripps Research Institute, about the services, the challenges in maintaining and keeping current these rapidly growing data sets, and how they are changing research into genetic-based disorders. The team's study in Genome Biology about the services can be found at http://bit.ly/1U88uAW.

Researchers’ understanding of certain rare diseases is changing as new sequencing technology is providing new views of the genome. A group of diseases collectively known as repeat expansion disorders including Fragile X Syndrome, Freidrich’s Ataxia, and Huntington’s disease are being viewed in new ways thanks to the ability to read long fragments of DNA. We spoke Jonas Korlach, chief scientific officer of Pacific Biosciences, about the company’s sequencing technology, how its changing the understanding of diseases thought to be well understood, and how it may lead to improved diagnostics and therapeutics.

While much of the attention of the Duchenne Muscular Dystrophy community has been focused on the recent FDA advisory committee review of Sarepta Therapeutics’ experimental drug Eteplirsen, Marathon Pharmaceuticals has been working to advance its own DMD drug candidate to the FDA. The company expects this month to file an application with the agency for approval to market Deflazacort, a corticoid steroid. We spoke to Tim Cunniff, head of research and development for Marathon Pharmaceuticals, about why the company thinks Deflazacort represents an improvement over existing therapies, what the company has learned from Sarepta’s experience, and its new effort to develop a precision medicine program in Duchenne.

When researchers explore the human genome, they usually look for genetic causes of disease, but a global study being led by scientists at the Icahn School of Medicine at Mount Sinai and Sage Bionetworks is looking for genes that might keep people healthy. Their study, the largest genome study to date, seeks to find people with genetic mutations that should have caused rare childhood diseases, but didn’t. Dubbed the Resilience Project, they are looking for clues in these genomes for why these people never became stricken. We spoke to Jason Bobe, associate professor and director of the Sharing Lab at the Icahn Institute and Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, about the study, what’s been learned so far, and how this may lead to new treatments for rare and deadly diseases.

For rare disease patients and their families, genome and exome sequencing may identify mutations that may be drivers of a condition, but nothing more. As families search for a name to put to a disease and look for treatments, finding others with the same condition and researchers working to understand and treat it becomes a critical part of the search for answers. Now researchers at the University of Washington have created MyGene2, a web portal for people with rare genetic mutations to connect with others with the same condition and researchers interested in their particular mutation. We spoke to Michael Bamshad, professor and chief of the Division of Genetic Medicine in the Department of Pediatrics at the University of Washington & Seattle Children’s Hospital and Jessica Chong one of the leads on the MyGene2 project at the Center for Mendelian Genomics at the University of Washington, about the portal, how it works, and what they are hoping to accomplish.

For many families with a child with a rare disease, realizing that something is wrong can be the beginning of an often long diagnostic odyssey. Typically it can take years to get a diagnosis and during that time people can find themselves isolated and without resources or support as they seek to put a name to what is wrong with their child. We spoke Amy Clugston, president of SWAN USA, about life without a diagnosis, the work of SWAN USA, and the upcoming Undiagnosed Children’s Awareness Day on April 29.

RaNA Therapeutics is pursuing treatments for rare diseases, such as spinal muscular atrophy and Friedreich’s Ataxia, with a new therapeutic approach that targets a previously unexplored druggable space. We spoke to Ron Renaud, CEO of RaNA, about his company’s effort to selectively upgregulate genes as a way to treat and prevent disease, the challenges in developing such drugs, and why the company has decided to initially target rare diseases with the technology.

Invitae is changing medical practice by brining genetic testing into the mainstream. The company says it seeks to aggregate most of the world’s genetic tests into a single service with higher quality, faster turnaround time, and lower price than many single-gene and panel tests today. The company recently announced new additions to the genes it tests for representing a major expansion of its panels for neurology, pediatrics and rare diseases. We spoke to Bob Nussbaum, chief medical officer for Invitae, about its expanded tests, how the company is able to maintain its low price point, and the implications for rare disease patients.

Emmy award-winning filmmaker Rudy Poe, in 2012, turned his lens on Hugh and Chris Hempel to document their effort to find a treatment for their twin daughters suffering from a rare lysosomal storage disorder and reform medical research in the process. The film, “Here. Us. Now.,” introduced Poe to the world of rare diseases. Now he’s in the process of taking a deeper look at the people in the rare disease community in his new film “Always in Hope.” We spoke to Poe about his interest in the rare disease world, what he’s hoping to accomplish in the new film, and how he’s using the Internet to find stories and raise money.

Large pharmaceutical companies have grown increasingly interested in rare diseases, but acquisitions of rare disease companies by large biopharmaceutical companies may lead to a cultural mismatch that hinders the development and performance of their products. We spoke to Alain Gilbert, co-chairman of the global strategic consulting firm Bionest Parnters and co-author of a February 2016 analysis in In Vivo “Orphans Should Live Alone.” Gilbert discussed how small, rare disease-focused companies operate differently than large pharmaceutical companies, the essential role their relationship with patients play, and why big companies that acquire rare disease drug developers would be best to leave them alone.

The 21st Century Cures Act, an ambitious piece of legislation of great concern to the rare disease community, passed the House last year only to stall the Senate. Now it’s back on the radar. The legislation is moving forward again, but this time in pieces. Separately in California, proposed legislation can greatly accelerate the process that tests are added to the list of newborn screening diagnostics that are performed. We spoke to Max Bronstein, senior director of public and government relations for the Everylife Foundation for Rare Diseases, about the developments on the legislative front, what the outlook is, and why these issues matter to the rare disease community.

As pharmaceutical companies, spurred by the Orphan Drug Act, have delved deeper into the development of drugs to treat rare diseases, they have forged closer ties with patient advocates. While these relationships are driven by mutual interest, tensions sometimes arise because of divergent needs. We spoke to Heather Gartman, regional managing director of InVentiv Health, about the firms recent white paper “The New Partnership Paradigm.” Gartman discussed how patient advocates can more effectively influence pharmaceutical companies, some of the mistake pharmaceutical companies make, and how the growing sophistication of patient advocates is changing the balance of power in these relationships.