Rare Diseases
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Introduction
Rare diseases present unique challenges in drug development. Standard clinical trial designs can require sample sizes greater than the world’s supply of patients. Much of the world’s information on a rare disease may be held in registries, and funding is often scarce for larger trials even if they are otherwise feasible. Given this reality, scientists and regulatory agencies have enthusiastically supported the use of innovative methods to produce efficient trials that maintain scientific rigor, often through the incorporation of historical data, adaptive designs, or disease modeling. Berry is a leader in all of these areas and has extensive experience in advancing rare disease science from design to implementation and approval.
Berry Examples and Case Studies
For GNE myopathy, we faced the challenge of a progressive disease best measured by different endpoints at different stages of the disease. Early on, endpoints like walk times centered on the legs is important. Later, patients lose the ability to walk, and endpoints like grip strength are more informative. Focusing on a single endpoint greatly reduces the available sample size, because only patients in a specific time frame of the disease may be enrolled. Berry, with our clients, produced a disease progression model that incorporated multiple endpoints to produce a “disease age” that could be used as an endpoint in GNE myopathy trials, allowing the full set of GNE myopathy patients to be enrolled in a single clinical trial. This disease progression model was combined with an existing registry of patients to produce an extremely efficient trial in a very difficult to enroll indication. The design was reviewed and accepted by the US FDA.
Similar ideas were incorporated in the DIAN-TU platform in dominantly inherited Alzheimers, a rare form of Alzheimers affecting younger adults. This indication, where the onset of Alzheimer’s can be predicted in a population, is an important testing ground in the development of Alzheimer’s drugs, and has been featured in media outlets like 60 Minutes. Disease progression was also included in DIAN-TU, as well as innovations in platform trial design allowing for the simultaneous evaluation of multiple therapies. All of these features substantially reduced the required sample sizes in this limited population.
In addition to GNE myopathy and dominantly inherited Alzheimer’s, Berry has designed clinical trials in Alexander’s Disease, ALS, ALSP, DIAD, CF, MPS III, Hypophosphatasia, congenital hyperinsulinism, Cushing’s disease, mitochondrial disease, Angelman’s Syndrome, SAVI, Epilepsy with Myoclonic-Atonic Seizures, DMD, Myotonic Dystrophy, Netherton’s Disease, pediatric heart transplants, Adrenomyeloneuropathy (AMN), Pelizaeus-Merzbacher disease (PMD), Kennedy’s Disease, Essential Tremors, GAN, Rett Syndrome, FOP, Canavan’s disease, Dravet’s Syndrome, FTD, FUS-ALS, Leukodystrophy (NORD/FDA), Hemophilia, X-linked Parkinson’s, Scleroderma, MSA, Retinitis pigmentosa, PAH, Staphylococcus aureus, Monkeypox, Recurrent C-DIFF, Prion disease, calciphylaxis, and numerous rare cancers.
