Rarecast

Fragile X syndrome is a rare, genetic, developmental disorder that is the leading known cause of both intellectual disability and autism spectrum disorder. People with the condition can have a range of behavioral symptoms, such as social avoidance and irritability. Zynerba is developing its experimental therapy Zygel, a topical cannabidiol gel that is delivered into the bloodstream through the skin to treat the behavioral symptoms of Fragile X. We spoke to co-director of the molecular diagnostics section of the Genetic Laboratory at Rush Medical College Elizabeth Berry-Kravis and Zynerba Chairman and CEO Armando Anido, about Fragile X, the company’s experimental therapy Zygel, and why the topical cannibidiol gel may hold promise for treating the behavioral symptoms of the condition.

When Stealth Biotherapeutics sought approval for its experimental therapy to treat the ultra-rare and life-threatening condition Barth syndrome, the U.S. Food and Drug Administration said it wouldn’t review its application because the clinical studies the company performed involved too few patients to make a determination about the efficacy of the drug. The notice was part of a history of interactions between Stealth and the FDA that that the company said was characterized by inconsistent guidance as it moved from division to division within the agency. We spoke to Reenie McCarthy, CEO of Stealth, about the challenges the company has faced in seeking FDA approval for its Barth syndrome therapy, the lack of consistency it found within the agency, and why this could have a chilling effect on the development of ultra-rare disease therapies if left unaddressed.

Primary mitochondrial myopathies are a group of rare, often life-threatening disorders caused by genetic mutations that affect the energy needs of skeletal muscles and can impact the ability to walk, lift, or do other everyday activities. High energy tissues like the heart, brain, and muscle are most affected by these disorders. Currently, there are no approved drugs to treat people with these conditions. Reneo Pharmaceuticals is developing an experimental therapy that works by increasing the transcription of genes involved in mitochondrial function, increasing fatty acid oxidation, and promoting the formation of new mitochondria. We spoke to Greg Flesher, president and CEO of Reneo, about mitochondrial myopathies, the company’s efforts to develop an experimental therapy to treat these conditions, and how it works.

In neurodegenerative diseases like ALS, cells in the brain suffer a decline in their ability to produce energy. These impairments help to drive the progression of these diseases. Clene Nanomedicine is developing a nanocrystal suspension of gold atoms that are small enough to enter mitochondria—the cellular organelles that power activity—to increase two critical energy metabolites to fuel cellular function and counter the disease. The company believes this has the potential to provide functional change to people with ALS and other neurodegenerative conditions. We spoke to Rob Etherington, president and CEO of Clene Nanomedicine, about ALS, the role that the compromised ability of cells to produce energy play in the disorder, and why the company believes its gold nanocrystal therapy has the potential to improve function in people with the condition.

One of the greatest challenges emerging therapies face is being able to reach the tissues and cells in the body where they need to go to provide benefit. Rather than using viral vectors or lipid nanoparticles, Evox is harnessing exosomes, a natural transporter within the body, to carry therapeutic cargo to desired targets. The company has developed platform technology to modify exosome so it can load therapeutic cargo into them to reach desired organs, the central nervous system, and intractable tissue. We spoke to Tony de Fougerolles, CEO of Evox Therapeutics, about exosomes, the company’s platform technology, and how it is using this approach to target a range of rare diseases.

Though enzyme replacement therapies have proven a viable strategy for treating lysosomal storage disorders, one problem is that these medicines face challenges reaching all of the cells throughout the body that are affected by these conditions, particularly in the brain. Avrobio is developing one-and-done gene therapies to treat cystinosis and other lysosomal storage disorders to overcome the limits of ERTs and possibly halt or reverse diseases. We spoke to Geoff MacKay, president and CEO of Avrobio, about cystinosis, the company’s gene therapy platform, and how it's leveraging its technology to develop therapies across a range of rare diseases.

Around the time Deb Scharper’s husband Tommy turned 38, he became forgetful, started to act odd, and lost interest in his long-time passion of driving and repairing cars. He grew paranoid and eventually suffered a breakdown in which he sought to harm his children and himself. The family had him admitted to a psychiatric facility and he was diagnosed and treated for depression. It would take until he was 44, that he was correctly diagnosed with frontotemporal dementia, a rare and progressive condition. He now receives full time care in a nursing home. We spoke to Scharper about the impact of frontotemporal dementia on her family, her experience as a caregiver, and why she has become an advocate who organizes support groups for other caregivers of people with the condition.

Hypoparathyroidism is a rare condition that is caused by the lack of functional parathyroid glands. The condition can lead to a long list of complications including muscle pain, brain fog, and damage to the kidneys. Amolyt Pharma is developing a therapeutic peptide to treat hypoparathyroidism. We spoke to Mark Sumeray, chief medical officer of Amolyt, about what its like for people living with the condition, why it is difficult to manage with current medical approaches, and why therapeutic peptides offer a compelling approach for hypothyroidism and other endocrine disorders. 

In 2022, three gene therapies for rare conditions won approval in the United States. As these and other advanced therapies make it to market, drug companies and payers need to wrestle with pricing issues, particularly for one-and-done therapies that are potentially curative. We spoke to Alice Valder Curran, partner with Hogan Lovells, about the challenges of value-based pricing for gene therapies, some of the pricing approaches gene therapy developers are employing, and how the existing policy landscape complicates matters.

The transformational potential of AAV gene therapies has been limited by challenges of delivering genetic material to the cells where they need to go, gene expression, immunity, and the complexity of manufacturing them. Apertura Gene Therapies is seeking to simultaneously engineering AAV capsids, genetic regulatory elements, and payloads to overcome these limitations. We spoke to Joseph La Barge, CEO of Apertura, about its platform technologies, how they work, and the potential for next-generation gene therapies to transcend the limits of first-generation AAV therapies.

In October, Alnylam said it would halt development of a therapy for a rare eye disorder to evaluate the impact of the Inflation Reduction Act. The decision is a reflection of the unintended consequences that policies can have on rare disease drug development. We spoke to Amanda Malakoff, executive director of the Rare Disease Company Coalition, about the policy landscape for rare disease therapies, unfinished business from the recent passage of a lean Prescription Drug User Fee Act, and policy priorities for 2023.

In December 2020, Ovid Therapeutics’ experimental therapy OV101 for the rare, neurodevelopmental condition Angelman Syndrome failed to meet its primary endpoint in a phase 3 clinical trial and the company chose to discontinue development. But rather than let the data from the study languish on the shelf, Ovid made the decision to contribute it to the Angelman Syndrome Foundation’s LADDER database. We spoke to Ovid CEO Jeremy Levin and Angelman Syndrome Foundation CEO Amanda Moore, about the LADDER database, Ovid’s decision to contribute its data to it, and why the two believe other drug developers should take similar steps to share their data with patients and researchers to advance the understanding of rare diseases.

Fabry disease is a progressive disorder that affects organs throughout the body including the heart, kidneys, and nervous system. People with the condition may suffer for years before obtaining a diagnosis. Jack Johnson, who co-founded the Fabry Support and Information Group, traced Fabry disease back more than five generations in his family. We spoke to Johnson about his own experience with the condition, his journey into advocacy, and a recent externally-led Patient-Focused Drug Development meeting to help regulators and drug developers understand the need for new therapies to address the challenges of living with the disease.

Racial disparities in care and outcomes have been well documented but the problems can be particularly acute in cases of rare, genetic diseases. One example of this is the rare blood cancer cutaneous T-cell lymphoma. African Americans are twice as likely as people of European or Asian descent to develop CTCL, are typically diagnosed with more advanced disease, and have a lower survival rate from the condition. Kyowa Kirin North America, which produces the CTCL treatment Poteligeo, is working to address racial disparities to improve the diagnosis, care, and outcomes of African American patients with CTCL. We spoke to Kyowa Kirin Vice President of Public Affairs Lauren Walrath and Co-Leader of the Immune Cell Regulation and Targeting Program at the Sidney Kimmel Cancer Center at Jefferson Health Pierluigi Porcu, about CTCL, the disparities in care and outcomes for African Americans with the condition, and what they are doing to address that. Porcu is a paid consultant to Kyowa Kirin.

Just three years after Children’s Mercy Research Institute launched its Genomic Answers for Kids program, it reported that it had hit the milestone of providing 1,000 rare disease diagnoses to families. One reason for the success of the GA4K program has been the use of advanced genomic sequencing that captures the full genome and methylome to reveal part of the human genome that has never been clinically tested to interpret changes beyond the genetic code. We spoke to Tomi Pastinen, director of the Genomic Medicine Center at Children’s Mercy Kansas City, about the GA4K program, how new sequencing technology is allowing it to diagnose rare disease patients who previously were undiagnosable, and how it has the potential to alter the diagnostic odyssey for patients with rare, genetic diseases.

Health Storylines is a patient-driven, digital platform for people to track and manage their health, but it is also a tool to enable drug and device developers to conduct decentralized clinical trials and gather real-world evidence. Alira Health expanded its digital health offerings with Health Storylines through its acquisition of Self Care Catalysts at the start of 2022. We spoke Gabriele Brambilla, CEO and co-founder of Alira Health, about how the technology provides patients with greater control over their own health, how it is using it to drive decentralized clinical trials and the integration of real-world evidence in the drug development process, and the potential to leverage its Health Storylines platform to answer research questions outside of a traditional clinical study.

The rare disease patient advocacy organization Global Genes and the rare disease patient data sharing platform RARE-X have agreed to merge, a move they say will provide next-generation rare disease advocates the tools and resources they need to accelerate their drive for treatments. Charlene Son Rigby, CEO of RARE-X, will become CEO of the combined organization. We spoke to Son Rigby about the merger, the convergence of her personal and professional lives, and how the combination of the two organization will provide next-generation rare disease advocates the tools and resources they need to accelerate their drive for treatments.

Michael Pirovolakis, a four-year-old with the ultra-rare, neurodevelopmental condition SPG50 disease, earlier this year became the first person to be dosed with an experimental gene therapy developed to treat the disorder. The gene therapy was the result of a relentless pursuit by his parents, Terry and Georgia, to raise money and engage scientists and others in the development of a treatment for SPG50. We spoke to Michael’s father and founder of CureSPG50 Terry Pirovolakis and associate professor at UT Southwestern Medical Center Steven Gray, about SPG50, the work to develop and advance an experimental gene therapy for the condition into the clinic, and why Pirovolakis says his work is not yet done. 

Matt Hay was a sophomore in college when he began to have problems with his hearing. He soon learned his hearing loss was caused by tumors on his nerves and was diagnosed with the rare condition neurofibromatosis. As a result of the condition, which can cause tumors to grow on nerves throughout the body, Hay has had to undergo 20 surgeries, including one to remove a tumor that blocked 80 percent of his spinal fluid and caused him to lose the ability to walk for a time. His diagnosis started him on not only a personal journey to fight his condition, but on a professional one as well as he became a patient advocate. We spoke to Hay, U.S. Director of advocacy for NF1 at Alexion, about his own journey as someone living with a rare disease, neurofibromatosis, and how his experience led him to become a patient advocate within the biopharmaceutical industry. 

ENPP1 deficiency is a rare mineralization disorder that leads to calcification of soft tissue. About half of newborns with the condition will die in the first year of life, while others will live well into adulthood. The condition can cause hearing loss, arterial calcification, and complications involving the heart and brain. There are currently no approved therapies for ENPP1 deficiency. Inozyme is developing a therapy for ENPP1 deficiency and other rare mineralization disorders. We spoke to Axel Bolte, co-founder and CEO of Inozyme, about ENPP1 deficiency, its lead experimental therapy to treat the condition, and its work with Rady Children’s Institute for Genomic Medicine to improve the diagnosis of newborns with the disease.