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Pictured: BioMarin's headquarters in California/iStock, Sundry Photography BioMarin disclosed in an SEC filing on Monday that it received a subpoena from the U.S. Department of Justice regarding the sponsored testing programs for its rare disease therapies Vimizim (elosulfase alfa) and Naglazyme (galsulfase). The company did not provide the specific reasons for the subpoena, instead only revealing that the DOJ is requesting “certain documents” in connection with these testing programs. “We have produced documents in response to the subpoena and are cooperating fully, but there is no assurance that such sponsored testing programs, or our other operations or programs, will not be found to violate such laws,” BioMarin stated in its SEC filing. The company also noted in the filing that it is unable to provide assurances regarding the outcome of the DOJ’s investigation or its potential impacts on BioMarin’s business and balance sheet. Vimizim is an enzyme replacement therapy approved for the treatment of Morquio A Syndrome, also known as mucopolysaccharidosis IVA. According to BioMarin’s website, Vimizim is the first and only FDA-approved therapy for the rare disease, caused by a deficiency in the N-acetylgalactosamine-6 sulfatase enzyme, which is crucial for the degradation and removal of several glycosaminoglycans (GAGs) from the body. Patients with Morquio A Syndrome suffer from the abnormal development of bones, including their spine, and often show other physical manifestations such as a cloudy cornea, knocked knees, a large head, short stature, a bell-shaped chest and flared ribs. BioMarin’s other product under DOJ investigation is Naglazyme, which is also an enzyme replacement therapy and is approved for mucopolysaccharidosis VI. The condition, also known as Maroteaux-Lamy Syndrome, is an inherited lysosomal disorder that arises due to the toxic buildup of GAGs in cells, leading to their dysfunction, according to BioMarin’s website. Mucopolysaccharidosis VI is caused by a deficiency in the enzyme responsible for breaking GAGs down and manifests as enlarged or inflamed tissues and organs. Patients with the condition may also suffer from hydrocephalus, joint deformities as well as muscle and tissue atrophy. BioMarin also released its fourth-quarter and full-year financial results in its SEC filing on Monday, touting total revenue of nearly $2.42 billion for 2023, representing 20% year-on-year growth at constant currencies. Both Vivizim and Naglazyme contributed strongly to BioMarin’s fiscal performance in 2023, with respective net product revenues of $701 million and $420.3 million, respectively. Its achondroplasia therapy Voxzogo (vosoritide) was also a top-selling asset, bringing in $469.9 million last year. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

There are plenty of great scientific research stories out this week. Here’s a look at just a few of them. Is a TB Vaccine a Cure for Type 1 Diabetes? Researchers at Massachusetts General Hospital in Boston published results from a long-term clinical trial of a tuberculosis vaccine in type 1 diabetes patients that in a long-term follow-up appears to have cured the disease. Denise Faustman, director of the MGH Immunobiology Laboratory, has been conducting work on the bacillus Calmette-Guerin (BCG) vaccine and its ability to restore near-normal blood sugar levels. In follow-up studies to a Phase I clinical trial, three years after patients received two doses of the BCG vaccine four weeks apart, all the adults with longstanding type 1 diabetes had an improvement of HbA1c levels that were close to normal, and that improvement lasted for the next five years. The work was published in npj Vaccines. Faustman will also be presenting results from a separate group of BCG clinical trial patients on Saturday, June 23, at the 78th Scientific Sessions of the American Diabetes Association in Orlando. Mayo Clinic Researchers Link Pancreatic Cancer Risk to 6 Genes A group of researchers led by Mayo Clinic’s Fergus Couch published research in the Journal of the American Medical Association (JAMA) that linked mutations in six genes to an increased risk of pancreatic cancer. In an evaluation of 3,030 patients with pancreatic cancer and 123,136 reference controls, the group identified six genes that were independently associated with pancreatic cancer. Overall, they were observed in 5.5 percent of patients with pancreatic cancer. As a result of the study, the authors feel the research justifies genetic testing of all pancreatic cancer patients using panel tests. In an accompanying editorial, Sapna Syngal and Sloane Furniss with the Dana-Farber Cancer Institute agreed, writing, “Given the devastating outcomes of pancreatic cancer, the real potential benefit for targeted therapies, and, even more importantly, the potential for cancer prevention in at-risk relatives, it is time to consider implementation of germline genetic testing for all patients with pancreatic cancer.” Is Big Data NOT the Way to Approach Healthcare? Scientists at the University of California, Berkeley published research in the Proceedings of the National Academy of Sciences that suggests that using big data to evaluating individual health may be a bad approach. The assumption is generally that the bigger the sample size, the more accurate it is. The study quantified the degree to which group data was able to describe individuals. “If you want to know what individuals feel or how they become sick, you have to conduct research on individuals, not on groups,” said lead author Aaron Fisher, assistant professor of psychology at UC Berkeley, in a statement. “Diseases, mental disorders, emotions, and behaviors are expressed within individual people, over time. A snapshot of many people at one moment in time can’t capture these phenomena.” The researchers, along with scientists at Drexel University in Philadelphia and the University of Groningen in the Netherlands used statistical models to compare information collected on hundreds of people and compared them to individual data. CRISPR Used to Predict Heart Disease Risk Researchers at Stanford University published research in the American Heart Association’s journal Circulation that described combining stem cell-based disease modeling and CRISPR/Cas9-mediated genome editing to perform risk assessment for cardiovascular disease. Joseph Wu, director of the Stanford Cardiovascular Institute and Simon Stertzer, Endowed Professor in the Department of Medicine (Cardiology) and Department of Radiology at Stanford University School of Medicine, noted that many genetic variations are “related” to a medical condition, but don’t necessarily lead to the disease. They evaluated DNA from 54 “healthy” or symptom-free people with no heart disease and sequenced their DNA using a custom DNA panel of 135 cardiomyopathy and congenital heart disease genes linked to sudden cardiac death. They uncovered 592 unique genetic variants, with 78 percent classified as “benign,” “likely benign,” or a “variant of uncertain significance.” But, 17 were described as “likely pathogenic” or disease-causing. “Results from this study will help improve the interpretation and diagnostic accuracy of gene variants, especially in the era of personalized medicine and precision health,” Wu said in a statement. “The goal is to optimize the decision making of clinicians in their choices of therapy by providing a much clearer results for the ‘variant of uncertain significance’ carriers.” Gene Therapy Used to Restore Hand Function After Spinal Cord Injury in Rats Kings College London researchers published research in the journal Brain describing the use of gene therapy to repair spinal cord injuries in rats. Elizabeth Bradbury from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) said in a statement, “What is exciting about our approach is that we can precisely control how long the therapy is delivered by using a gene ‘switch.’ This means we can hone in on the optimal amount of time needed for recovery. Gene therapy provides a way of treating large areas of the spinal cord with only one injection, and with the switch we can now turn the gene off when it is no longer needed.” The gene therapy stimulates cells to create an enzyme called chondroitinase, which breaks down the nerves’ scar tissue, allowing networks of nerve cells to regenerate. They tested it on rats with spinal injuries that were similar to the kind found in humans after traumatic impacts like car crashes or falls. As exciting as this is, the authors warn that it’s not ready for human trials, because although they built in a safety switch, a small amount of the gene stayed active even when it was switched off. Further work will be needed on shutting down the gene completely before moving to trials in people.