How to Develop a Rare Disease Treatment

Abstract

GEN BiotechnologyVol. 2, No. 1 Book ReviewsFree AccessHow to Develop a Rare Disease TreatmentSean EkinsSean Ekins*Address correspondence to: Sean Ekins, Collaborations Pharmaceuticals, 840 Main Campus Drive, Lab 3510, Raleigh, NC 27606, USA, E-mail Address: sean@collaborationspharma.comCollaborations Pharmaceuticals, Raleigh, North Carolina, USA.Search for more papers by this authorPublished Online:15 Feb 2023https://doi.org/10.1089/genbio.2023.29075.sekAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Saving Ryan: The 30-Year Journey into Saving the Life of a Childby Emil D. Kakkis (Impositivity Media, LLC, 2022).There are several excellent books about patients diagnosed with a rare disease [e.g., Gina Kolata's Mercies in Disguise (St Martins Press, 2017)] or about building a rare disease biotech, such as A Rare Breed by Daniel Levine and Daniel Maher (Biomarin, 2017) and Conscience and Courage by John Hawkins (Cold Spring Harbor Laboratory Press, 2019). Published in 2022, Saving Ryan by physician/scientist and entrepreneur Emil Kakkis successfully merges the story of a rare disease patient chasing a life-saving treatment with the clinician scientist's perspective of developing it.(My company has benefitted from Emil's generosity in providing a letter of support for a rare disease grant.) The author's compassion and willingness to help others who are developing rare disease treatments shine in every page. He even started a publishing company to self-publish the book to provide a story of hope.Inspiration and FrustrationThe book blends autobiography, inspirational read, and instructions on how to make an enzyme replacement therapy (ERT) for a rare disease. Kakkis tells the story of Ryan Dant, who was diagnosed as a young child with a lysosomal storage disease, mucopolysaccharidoses type I (MPS I). His parents are determined to fund a treatment to save his life.MPS I is caused by a mutation in an enzyme iduronidase, which clears glycosaminoglycans. In patients lacking this enzyme, these build up in the joints and various organs and may lead to life-threatening complications. Emil and the Dants cross paths in 1995, raising significant funds that helps Emil and his laboratory develop the treatment. A start-up biotech (Biomarin) and then a bigger biotech (Genzyme) provide additional funding and expertise, resulting in clinical trials and ultimately, in 2003, approval by the FDA.That is the abbreviated story. What is remarkable is the “warts and all” telling of it, especially the numerous hurdles that must be surmounted and unexpected setbacks that reminded me of a game of snakes and ladders. We hear a perspective from a clinician/principal investigator in an academic laboratory who must balance the ups and downs of hiring staff, the challenges of raising funds, and ultimately the dual pressures of publishing vs continuing research to develop a treatment.Kakkis spares no details in the ups and downs of working with the FDA. Over 2 years, the relationship went from very supportive to delaying the treatment reaching the market, necessitating an additional clinical trial and millions of dollars of further investment to be raised. Kakkis surprisingly names those people at the FDA, whom he alleges cost several children's lives by delaying treatment availability. Working on such rare diseases is heartbreaking and Kakkis took those losses personally.In the epilogue, Kakkis provides an update on the participants in the first clinical trial. Sadly, 6 of the 10 are no longer alive, likely because they were treated relatively late, and the effects of the disease were already advanced. The remaining four are living productive independent lives, which previously would have been unimaginable.TranslationAs someone developing an ERT for a rare disease (Batten disease), the timing of this book could not have been better. We learn every step in the process of how an ERT is made and tested before translation to the clinic. The book is a well-written “how to” manual. Not that everyone will be able to follow in his footsteps, but Kakkis provides a roadmap for other families and scientists.An index would have added to the book's value. The scientific explanations of lysosomal diseases are clear and the author pays tribute to the pioneers such as Elizabeth Neufeld working on rare genetic diseases who discovered the mutation that causes MPS I and laid the foundation for eventual treatments. Kakkis started working on MPS I not in some swanky modern laboratory but in a bungalow laboratory from the 1940s at Harbor-UCLA Medical Center in Torrance, CA, which ultimately had to be retrofitted to be able to provide Good manufacturing practice conditions to make clinical material.The detailing of the “shoestring science” and agonizing efforts to make tiny quantities of enzyme for the initial preclinical studies in dogs is revealing for how little it cost to get this far in 1993, likely tens of thousands of dollars and many very long days. Kakkis made it work with part-time staff and second-hand equipment, but he was clearly very demanding.As Kakkis raises more money, the team grows and so does the protein production scale. You get the sense that if more academics were like him and not continually chasing publications, grant funding, and tenure, we would have more treatments available for patients. Kakkis ultimately sacrificed his academic career to bring hope to the families of MPS I patients, but his route in biotech also positioned him well to become an entrepreneur, starting his own company.ImpactThe monumental effort to get the ERT treatment approved ultimately led to the product Aldurazyme being used by >1000 people around the world, leading to newborn screening for the disease. Kakkis intertwines this story with the more personal story of the Dants' fundraising efforts and their hopes and fears for their son. There is a happy ending for Ryan and plentiful photos to chart his life from young child through to married adult. Kakkis has been at Ryan's side for many of his milestones. He spent 11 years at Biomarin bringing six more treatments to market (which he mentions in passing), rising to chief medical officer. He then started a foundation to work with the FDA, congress, and companies to help improve the process of bringing treatments to patients.In 2010, Kakkis founded Ultragenyx to work on rare and ultrarare diseases, developing an ERT for MPS VII, for which the FDA provided compassionate access. Perhaps more importantly, Kakkis serves as an inspiration for families, and he provides much useful advice throughout this book. For example, The Ryan Foundation had a massive impact on his laboratory and ability to develop the ERT, something other families should heed. They could focus their funds and resources on supporting young scientists without NIH funding.Some diseases will be tough to address with ERTs, but Emil makes a strong case for their potential (at the outset he wanted to work on gene therapies but was nudged toward ERT). Kakkis' biggest impact may be to inspire the hundreds if not thousands of other families and scientists who are also looking for a cure or a purpose, respectively.Providing HopeSaving Ryan is an important historical document. Will we look back on the early 2000s as a turning point with companies including Biomarin and Genzyme developing ERTs? Like many other companies, they have also invested heavily in gene therapy, with no treatments to show for it. What have we lost by not continuing to develop the technologies for producing more ERTs that might also enable them to be made more cost-effectively?I would have liked Kakkis to talk more about the future, what technologies could be used to enable developing ERTs to scale. Nevertheless, Kakkis has shown what is possible and perhaps others will pick up the baton. Saving Ryan shines a light on how a family foundation can have a dramatic effect on funding cutting-edge science. The next time you are asked to sponsor someone or participate in a charity golf tournament for a rare disease, remember that your generosity could help the next breakthrough therapy, leading to a story of hope that will one day be told just like this one.FiguresReferencesRelatedDetails Volume 2Issue 1Feb 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Sean Ekins.How to Develop a Rare Disease Treatment.GEN Biotechnology.Feb 2023.27-28.http://doi.org/10.1089/genbio.2023.29075.sekPublished in Volume: 2 Issue 1: February 15, 2023PDF download