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Patients have always been the center of the yearly scientific symposium hosted by the Friedreich’s Ataxia Research Alliance (FARA) and the University of South Florida Ataxia Research Center.

But, for the 8^th annual symposium held Sept. 15 at USF’s Gibbons Alumni Center, patients took on an even more prominent role. The panel discussion in which they share their stories about living with the rare, but devastating, progressive neurodegenerative disease, including patient participation in clinical trials, was moved up in the program format.

The 8th annual scientific symposium hosted by FARA and USF was held in the USF Gibbons Alumni Center.  More than 750 in the FA community listened to the latest perspectives on ataxia research from patients and scientists, in person and internationally via live-stream.

And this year, led by FARA spokesperson Kyle Bryant as moderator, the four patient panelists were the ones driving the conversation with leading researchers from academia and industry who sat onstage beside these young adults to discuss the latest advances in the search for effective treatments and, ultimately, a cure.

More than 250 attendees gathered at the USF Gibbons Alumni Center for the symposium, which was also live-streamed and viewed worldwide by those in the FA community, over 500 people in eight countries. The symposium “Understanding Energy for a Cure” kicked off a series of events in Tampa Bay to raise awareness about FA, culminating Sept. 17 with the FARA Energy Ball gala, which this year raised $2 million to benefit innovative ataxia research.

The patient panel, moderated by FARA spokesperson Kyle Bryant (far left), helped drive the conversation with leading researchers. Participants were, from left, Alex Fielding, Sean Baumstark, Alison Avery and Anna Gordon.

“My parents and sister never really let me believe that Friedreich’s ataxia was going to stop me,” said panelist Alison Avery, 22, diagnosed with Friedreich’s ataxia at age 18, who is interning with the National Football League’s social responsibility department in NYC following college graduation. “It may have changed the way that I do certain things, but right now I’m living on my own in New York City, and that’s something not everyone would do, whether or not they have FA.”

Alison participates in the “Cardiac MRI and Biomarkers in Friedreich’s Ataxia” study at Children’s Hospital of Philadelphia and another evaluating the relationship between exercise performance and neurological/cardiac status and overall functioning in children and adults with FA. “I’m excited to be able to share my perspective on being involved in different research studies,” she said. “I feel like that’s something more people should know, especially the researchers — about how patients actually feel about trials and studies.”

USF System President Judy Genshaft said USF has made neurosciences, including ataxia research, a high institutional research priority.

Friedreich’s ataxia typically strikes in childhood or adolescence and leads to a progressive loss of coordination and muscle strength, eventually robbing young people of their energy and ability to walk. While the neurological symptoms are most visible, FA is a multisystem disease that can adversely affect cardiac function, metabolism, vision, hearing and the skeletal system. There is currently no approved treatment for FA.

“Throughout the history of this event, the one constant has been how incredibly motivating and inspiring it is to hear from patients and their families who never fail to share one valuable message: ‘Live life to its fullest despite the challenges of Friedreich’s ataxia,’” said USF System President Judy Genshaft in her symposium welcome remarks.

FARA Executive Director Jennifer Farmer introduced the patients and provided insights on their participation in studies and clinical trials.

The USF Health Morsani College of Medicine is one of 10 sites in the international FARA Collaborative Clinical Research Network, all working to discover treatments that can attack FA on different fronts and improve the quality of life for patients.

“We’ve made this a high research priority within the institution,” President Genshaft said. “Over the last 20 years FARA’s international collaborative of researchers has increased the pace in the fight against FA. Today more than 20 drugs are in the treatment pipeline and ongoing studies are working toward the discovery of new therapies… We have every reason to be hopeful, but we do know there is more work to be done.”

Theresa Zesiewicz, MD, professor of neurology and director of the USF Ataxia Research Center, presented promising preliminary results from two clinical trials conducted at USF, among other sites. – Photo by Kent Ross

Theresa Zesiewicz, MD, professor of neurology and director of the USF Ataxia Research Center, updated attendees on the center’s initiatives.

“We started out at USF with one clinical trial eight years ago, and now we have five or six clinical trials and each (investigational) drug works differently,” Dr. Zesiewicz said. “Some drugs work to increase frataxin (the protein depleted in those with FA), some drugs work on inflammation, some work as strong antioxidants. So, there may not be one magic bullet to stop this disease; rather, it may require a cocktail of therapies, a conglomerate of different compounds to help delay or stop the disease process.”

David Lynch, MD, PhD, (center) lead investigator for the FA Natural History Study at Children’s Hospital of Philadelphia, responds to a patient question. He was joined in the discussion of clinical trials by Martin Delatycki, PhD, (far left) of Murdoch Children’s Research Institute, Melbourne, Australia.

Some promising preliminary results for two clinical trials conducted at USF, among other sites, were announced by lead investigator Dr. Zesiewicz. Both studies were done in collaboration with FARA.

• EPI-743 Safety and Effectiveness Study: The Phase 2 open-label extension study, sponsored by Edison Pharmaceuticals, tested the effectiveness of the potent antioxidant EPI 743 primarily on vision, and secondarily, on neurological function in adult patients with FA. After two years of study and a year of data analysis, the researchers found that patients taking EPI-743 from the study’s start demonstrated markedly less disease progression than would be expected in the natural history of the disease. The improvement in neurological function was dose-dependent, and although the last 18 months of the study were open-label, patients and investigators were blinded to the drug dose allocation. Additional studies of EPI-743 are planned in pediatric patients and those with point mutations.

FARA President Ron Bartek thanked everyone in the room, including researchers, pharmaceutical partners and patients and their families, for working together to advance discoveries to “slow, stop and reverse” Friedreich’s ataxia.

• Retrotope RT001 Phase 1/2: The randomized double-blind, placebo-controlled trial evaluated the safety, tolerability and early effectiveness of the stabilized fatty acid RT001 in adult patients with FA. In the small, 28-day study, researchers found that the drug was safe, well tolerated at high doses and rapidly absorbed to target levels, with early signs of effectiveness. Earlier this year, the FDA granted Retrotope orphan drug designation for RT001 in FA.

The scientist and physician panelists at the symposium covered four areas of FA research:

• Basic and Discovery Science: Helene Puccio, PhD; Marek Napierala, PhD; and Jordi Magrane, PhD
• Drug Development and Advancing Treatments: Mark Payne, MD; and Barry Byrne, MD, PhD.
• FA Biomarkers: Kimberly Lee Lin, MD; Angel Martin, PhD student; and Christophe Lenglet, PhD.
• Clinical Trials and Translating Treatments to Improved Care: Martin Delatycki, PhD; and David Lynch, MD, PhD.

The researchers discussed their scholarly work, progress beyond their laboratories and its relevance to advancing treatments. They also emphasized their passion for FA science and personal commitment to patients.

Scientists participating in the Basic and Discovery Science panel discussion were, from left, Jordi Magrane, PhD, of the Brain and Mind Research Institute, Weill Cornell Medical College; Marek Napierala, PhD, of the University of Alabama; and Helene Puccio, PhD, of the Institute of Genetics and Molecular and Cellular Biology, University of Strasbourg.

Moving from treating symptoms to slowing and stopping progression to reversing disease is “not an overnight event,” said David Lynch, MD, PhD, lead investigator for the FARA Natural History Study at Children’s Hospital of Philadelphia. “So, in 15 years we may look back and talk not about the advance but about the 15 advances from each of 15 clinical trials superimposed on top of one another, eventually leading to that four letter word — cure.”

Answering patient questions on drug development and advancing treatments were physician-scientists Barry Byrne, MD, PhD, (left) of the University of Florida College of Medicine; and R. Mark Payne, MD, of Indiana University School of Medicine.

Despite the challenges, the researchers agreed that the steadfast determination and resilience of patients and their families energizes them to keep working toward a cure.

“Everything we do is for the patients, and we are all in this together trying to find a treatment and cure for Friedreich’s ataxia,” said USF’s Dr. Zesiewicz. “That’s the only reason we’re here.”

Participants in the FA BioMarkers panel discussion were, from left, Kimberly Lee Lin, MD, of Children’s Hospital of Philadelphia; Christophe Lenglet, PhD, of the Institute for Translational Neuroscience, University of Minnesota; and Angel Martin, a PhD candidate at Duke University.

Alison Avery, second from right, credits her family — sister Laurel Avery (left) and parents Paul and Suzanne Avery — with “never really letting me believe that Friedreich’s ataxia is going to stop me.”

Dr. Zesiewicz with members of the USF Ataxia Research Center, one of 10 sites in the international FARA Collaborative Clinical Research Network. – Photo by Kent Ross

Photos by Eric Younghans and video by Sandra C. Roa, USF Health Communications and Marketing

The U.S. Food and Drug Administration yesterday designated fast-track status to EPI-743 for the treatment of Friedreich’s ataxia – a move that will help accelerate clinical development of the investigational drug, currently being tested in a multisite, double-blind, placebo-controlled trial led by the University of South Florida.

The phase 2b clinical trial of EPI-743 in adults with Friedreich’s ataxia, sponsored by Edison Pharmaceuticals, Inc., in collaboration with the Friedrich’s Ataxia Research Alliance, has been underway since early 2013 at the USF Health, the Children’s Hospital of Philadelphia and the University of California in Los Angeles.  Neurologist Theresa Zesiewicz, MD, director of the USF Ataxia Research Center, is the lead investigator for the national trial.

Researchers are primarily testing the effectiveness of EPI-743, a potent antioxidant, on vision, in patients with Friedreich’s ataxia, many of whom experience varying degrees of visual changes. Secondarily, the study is evaluating neurological function.

For more on the fast track status of EPI-743, go to: http://www.firstwordpharma.com/node/1195801#axzz2wKgT2a1W

First patient enrolled to evaluate investigational drug’s effectiveness  in rare Friedreich’s ataxia genotype

Mountain View, CA; Downingtown, PA; & Tampa, FL (Nov. 4, 2013) — Edison Pharmaceuticals, the Friedreich’s Ataxia Research Alliance (FARA) and the University of South Florida (USF) today announced the initiation of a phase 2 study entitled, “Phase 2A Clinical Trial of EPI-743 on Visual Function in Friedreich’s Ataxia Patients with Point Mutations.”

Given the rarity of the Friedreich’s ataxia point mutation genotype, the trial is a single-arm, subject-controlled study lasting three months, followed by a three-month extension phase.  Study participants must be between the ages of 18 and 65, possess genetic confirmation of Friedreich’s ataxia point mutation defect, and meet certain disease severity criteria. The primary endpoint of the trial is visual function, with secondary endpoints including neurological and neuromuscular function, and disease-relevant biomarkers.  More information on study specifics is available on ClinicalTrials.gov.

This trial will be conducted at USF Health – a member of the Collaborative Clinical Research Network in Friedreich Ataxia– and is funded by a grant awarded by the Friedreich’s Ataxia Research Alliance. The study sponsor is USF, and the principal investigator is Theresa A. Zesiewicz, MD, FAAN, professor of neurology and director of the USF Ataxia Research Center.

“FARA has been eager to see drug development efforts extend into ultra-rare subgroups of Friedreich’s ataxia, such as those harboring point mutations,” said FARA President Ronald Bartek. “This is the first study dedicated to examining safety and investigational drug response in adults with point mutations in the frataxin gene that represent approximately 2 to 4 percent of the Friedreich’s ataxia patients.”

EPI-743 is currently being evaluated in a phase 2B placebo-controlled Friedreich’s ataxia trial in individuals with the more common triplet repeat expansion defect in frataxin synthesis.

Friedreich’s Ataxia

Friedreich’s ataxia is an autosomal recessive nuclear DNA inherited mitochondrial disease, affecting an estimated 1 in 30,000 individuals in the United States and Europe. Friedreich’s ataxia is caused by a defect in the gene frataxin, which encodes a 210 amino acid protein that participates in iron-sulfur (Fe-S) cluster protein assembly. As the majority of these Fe-S cluster proteins are localized in the respiratory chain in the mitochondria, patients with Friedreich’s ataxia present with “energy failure” symptoms including ataxia, muscle weakness, heart failure, diabetes, and visual, speech, and hearing deficiencies. Friedreich’s ataxia is a highly debilitating and life-shortening disease and is a member of a larger family of diseases called mitochondrial disease that share as a common biochemical mechanism defects in cellular energy metabolism. There are no FDA-approved drugs for Friedreich’s ataxia.

EPI-743

EPI-743 is an orally bioavailable small molecule being developed by Edison Pharmaceuticals for the treatment of Friedreich’s ataxia and other inherited mitochondrial diseases.

Edison Pharmaceuticals

Edison Pharmaceuticals is a biotechnology company dedicated to developing treatments for children and adults with mitochondrial diseases. More information can be found at www.edisonpharma.com.

FARA

The Friedreich’s Ataxia Research Alliance (FARA) is a national, public, 501©(3), non-profit, tax-exempt organization dedicated to curing Friedreich’s ataxia (FA) through research. FARA grants and activities provide support for basic and translational FA research, pharmaceutical/ biotech drug development, clinical trials, and scientific conferences. FARA also serves as a catalyst, between the public and scientific community, to create worldwide exchanges of information that drive medical advances. For more information about FARA, visit them online at www.curefa.org.

USF Health

USF Health is an integral part of the University of South Florida, a global research university ranked 50^th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities. USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. For more information, visit www.health.usf.edu.