Alglucosidase Alfa

iStock, Rudzhan Nagiev While biopharma’s overarching mission is to develop innovative medicines to improve patient outcomes, for these six people, the motivation came from much closer to home. In February, Doug Ingram dropped a bombshell on the industry: He would be stepping down from his post as CEO of Sarepta Therapeutics after a career spanning more than three decades. Ingram’s difficult decision was driven by what he called a “fairly shocking and ironic twist of fate.” “As you know, in late 2024 we entered into a partnership with Arrowhead, and we gained access to a number of very promising therapies, including SRP-1003, for a devastating disease, DM-1,” he said. Shortly after the deal, that same disease came knocking on Ingram’s door, afflicting two members of his immediate family. Leaving Sarepta, Ingram said, will help him pour more of his focus at home. By the end of the year, Sarepta will be under new management, though there has been no word on Ingram’s replacement yet. Ingram’s situation is heart-breaking but by no means unheard of. In fact, biopharma is replete with examples of devastating diagnoses driving ardent drug development and entrepreneurship. It’s unclear yet where this personal bout with DM1 will take Ingram, but if he decides to return to biopharma and focus his efforts on this disease once again, there will be paths open to him, forged by many others who were steered to biopharma by personal motivations. BioSpace looks at six such cases, where drug development was spurred by a mission far more individualized than profit and shareholder value or the benefit of entire patient communities. ‘Deeply personal’ investment adds to Quiver’s arrows Around one in 4,000 children is born with a specific chromosomal aberration that will leave them stunted, both physically and developmentally. Babies with the disease, called Dup15q , may appear floppy and could have trouble feeding and be behind on key motor milestones. Kids with Dup15q also suffer from learning and intellectual disabilities. In rare cases, Dup15q leads to sudden death. There is no approved treatment for this disease. That’s where Quiver Bioscience comes in. Based in Massachusetts, the biotech is working on an antisense oligonucleotide that targets the UBE3A gene, heightened expression of which has been linked to Dup15q, the company said in a March 2025 news release . A precision approach to reduce UBE3A has “disease-modifying potential” for this condition, Quiver noted. Last month, Quiver received a “ targeted investment ” from a family office in Argentina, specifically to help the company take its oligonucleotide program forward. But instead of wanting to see the money grow, this placement was much more personal: One of the family members also has Dup15q. “As the father of a daughter living with this condition, this is not an ordinary investment — it is a deeply personal commitment to every family navigating this journey every single day,” José A. Porta, president of the family office, said in a prepared statement. In an email to BioSpace , Quiver declined to provide additional details regarding the Porta family’s investment, including how much money the company received. The support, however, will allow the biotech to carry out preclinical activities for its antisense oligonucleotide, including candidate selection and safety assessments, opening the path toward clinical development, according to its April news announcement. Parents launch Solid in search of cure for son Solid Biosciences was founded in 2013 by husband-and-wife team Ilan and Annie Ganot. Their goal: Find a cure for their son Eytani, who had been diagnosed with Duchenne muscular dystrophy (DMD). At the time of Solid’s establishment, there were no therapies for Duchenne on the market yet. The first Duchenne drug to win the FDA’s approval—Sarepta Therapeutics’ exon-skipper Exondys 51 —was still three years away, and even then, it left a big portion of the patient population unserved. Exondys 51 is only indicated for patients who are amenable to exon 51 skipping, which represents around 13% of all patients with Duchenne. Indeed, not long after their son was diagnosed, the Ganots realized that exon skipping therapies and those that boost dystrophin expression—a key deficiency in Duchenne—wouldn’t lead to meaningful and profound symptom improvements that parents like them would want for their kids, Ilan told Rare Disease Advisor in 2022. The Ganots decided that only a gene therapy could give the relief they were looking for. Solid is working toward this goal with SGT-003, which makes use of a genetic construct that expresses the microdystrophin protein, according to the company’s website . This could help compensate for the dystrophin deficiency in patients with Duchenne. To deliver the genetic payload, Solid is using a proprietary adeno-associated virus (AAV) vector that selectively targets cardiac and skeletal muscles while avoiding the liver—a pro could lend the asset better efficacy and safety. Sarepta’s now-approved Duchenne gene therapy Elevidys was rocked last summer by patient deaths relating to liver complications from the AAV vector technology. SGT-003 is being tested in two studies: the Phase 1/2 INSPIRE trial and the Phase 3 IMPACT study. INSPIRE has shown robust microdystrophin expression and early signs of muscle improvements. Solid is working with the FDA for a potential accelerated pathway for SGT-003. IMPACT is set to start this year. Elpida born from parents’ quest to save son As in the case of Solid, Elpida Therapeutics was born out of a couple’s desire to save their son. In 2019, Terry and Georgia Pirovolakis were told that their son Michael had SPG50 , a neurodegenerative and developmental disorder that, with fewer than 100 known cases worldwide, is classified as “ultra-rare.” There is no cure for SPG50, only treatments to manage its symptoms. SPG50—also known as spastic paraplegia 50—is caused by mutations to the AP4M1 gene , which under healthy conditions encodes a part of a protein that helps move molecules along inside cells. Children must inherit an altered version of this gene from both of their parents for the disease to manifest, causing developmental delays, poorly formed muscles and lower-limb paralysis. Searching for relief for their son Michael, the Pirovolakises decided that they needed to develop their own gene therapy, leading to the launch of Elpida in May 2023 . The company’s lead program is MELPIDA, which delivers a functioning copy of the AP4M1 gene. Michael became the first-ever patient to receive MELPIDA in 2022, around three years after he was diagnosed—and the results were promising. At about a year after receiving the gene therapy, Michael showed improvements in limb spasticity and achieved notable development and motor gains, according to a June 2024 publication in Nature Medicine . MELPIDA was also largely safe for Michael, and the gene therapy was able to keep SPG50 at bay, preventing disease progression. The asset is in Phase 3 development, according to Elpida’s website . CEO-Dad enters biotech to develop treatment for kids Joining the roster of parents going into biopharma to save their kids is John Crowley—and of those that made it to this list, he might be the most well known and his fight the most documented. Crowley’s story even became the backbone for the 2010 film Extraordinary Measures, starring Harrison Ford and Brendan Fraser. In 2000, Crowley helped establish Novazyme Pharmaceuticals with the goal of developing a treatment for Pompe disease , a rare metabolic disorder that afflicted two of his children. Patients with Pompe suffer from muscle weakness and have enlarged hearts and livers, often leading to other complications. Left unchecked, the condition can leave children debilitated or lead to dead. Indeed, the prognosis for Crowley’s kids was dire, according to reporting by Rare Disease Advisor last month: They wouldn’t survive past two years. Roughly a year into its operations, Novazyme got acquired by Genzyme for $225 million. Despite being a hefty vote of confidence for his mission, this deal posed a crucial conundrum for Crowley: Being an employee, he couldn’t enroll his kids into the company’s clinical trial, Fierce Pharma reported last year. But Crowley would not be stopped and ultimately stepped down from Genzyme. His gamble worked—as did the investigational therapy. His children were enrolled in the trial and experienced improved muscle strength and normalized heart sizes. Today, this therapy is marketed under the brand name Lumizyme. Sanofi owns the rights to it after a 2011 deal with Genzyme worth $20 billion . Crowley, meanwhile, has gone on to establish Amicus Therapeutics , still keeping his sights set on advancing therapies for rare diseases. After a $4.8 billion acquisition in December, Amicus today operates as a subsidiary of BioMarin. Crowley is also currently serving as CEO of the Biotechnology Innovation Organization (BIO) after rising as an executive leader in biotech. Mom launches EveryONE Medicines to honor daughter’s life A parent’s perseverance sometimes ends in heartbreak. That’s the case for EveryONE Medicines , which closed up shop in March . After cofounding the company in early 2021 with the goal of developing individualized precision treatments for patients with rare diseases, Julia Vitarello publicly debuted EveryONE in 2024. EveryONE’s mission is deeply personal to Vitarello. Her daughter, Mila, suffered from Batten disease , an umbrella term that refers to a group of genetic disorders involving the toxic buildup of waste in a child’s brain cells. Symptoms include vision loss, muscle weakness and seizures, alongside developmental and cognitive problems. Batten disease is fatal and often leads to death early in a patient’s life. Vitarello worked hard to avert this fate for her daughter and enlisted researchers at the Boston Children’s Hospital to come up with a cure, C&EN reported in 2024. This effort resulted in an antisense oligonucleotide which they called milasen, designed to address the specific genetic mutation driving Mila’s condition. The treatment helped improve Mila’s condition, reducing her seizures —but it wasn’t enough to save her. Mila was diagnosed at age 6 and died at 10. Today, despite EveryONE folding, Vitarello remains involved in rare disease development. She is the chairwoman and CEO of Mila’s Miracle Foundation , a non-profit that works with academics, government agencies and companies to foster the development of individualized medicines. Vitarello also serves as a steering committee member of the N=1 Collaborative , a network of organizations and experts advancing personalized treatments. Cure Rare Disease honors founder’s late brother Capping off this list is Cure Rare Disease, a non-profit company that works to develop therapies for patients who had been “previously deemed untreatable,” according to its website . The group was established by Rich Horgan with the goal of developing a treatment for his brother, Terry, who had been diagnosed with Duchenne muscular dystrophy. The group got very close to their goal and in October 2022 they were able to dose Terry with a CRISPR-based gene therapy made specifically for him to address the rare genetic mutation that drove his condition. A month later, however, Terry died . Cure Rare Disease suggested on its website that the team was just too late, noting that Terry’s death “would have been avoided had the treatment been accessible sooner.” Research since has however pointed the finger at the viral vector used to deliver the gene therapy, which triggered a powerful immune reaction. Regardless of the cause of his brother’s death, Rich Horgan has continued his mission of developing therapies for other rare diseases. Alongside Duchenne, and in collaboration with researchers, policy experts and other foundations, Cure Rare Disease is also working on programs for limb-girdle muscular dystrophy, spinocerebellar ataxia and adenylosuccinate synthase 1-related myopathy.

PHILADELPHIA--(BUSINESS WIRE)--Aro Biotherapeutics, a clinical-stage biotechnology company developing potent and tissue-targeted short-interfering RNA (siRNA) medicines in areas of high unmet need in rare muscle diseases, immunology, and oncology, today announced positive topline results from the Phase 1b portion of its study evaluating ABX1100, a novel investigational therapy for the treatment of late-onset Pompe disease (LOPD). In the study, ABX1100 achieved a robust and sustained knockdown of glycogen synthase 1 (GYS1) messenger RNA (mRNA), the enzyme responsible for glycogen production in muscle. “The totality of these data show compelling clinical evidence that ABX1100 may offer a substantial benefit to people with late-onset Pompe disease,” said Purnanand Sarma, Ph.D., chief executive officer of Aro Biotherapeutics The topline Phase 1b data also showed positive effects on lung function and exploratory biomarkers in LOPD, findings that suggest functional improvement. ABX1100 was well tolerated among the nine patients with LOPD in the Phase 1b portion of the trial, consistent with previously reported Phase 1a results in 29 normal healthy volunteers. Full results will be presented at a future scientific conference. “The totality of these data show compelling clinical evidence that ABX1100 may offer a substantial benefit to people with late-onset Pompe disease,” said Purnanand Sarma, Ph.D., chief executive officer of Aro Biotherapeutics. In the Phase 1b portion of the trial, conducted at four sites in the United States and Canada, ABX1100 was administered without any pre-medication over <25-minute infusions on Days 1 and 29 (a loading dose regimen), as an add-on to enzyme replacement therapy (ERT). The nine patients, whose mean age was 54 years at study initiation, were followed for 20 weeks. Participants had been receiving ERT for a mean of 7.4 years (range 1-15 years). As per the study protocol, investigators collected muscle biopsies at baseline, Week 6, and Week 10 for the first four patients, and at baseline, Week 10, and Week 16 for the next five patients to investigate persistence of GYS1 mRNA knockdown. ABX1100 demonstrated robust and sustained GYS1 mRNA knockdown at a target level of approximately 62% in the quadriceps muscle in all evaluable patients through Week 10. At Week 16, observed levels in muscle Gys1 short-interfering RNA (siRNA) and GYS1 mRNA support quarterly or less frequent dosing beyond the administered loading dose regimen. The Phase 1b study monitored changes in patients’ lung function via Forced Vital Capacity Percent Predicted (FVC %pred), a measure that has been shown to continue to decline in LOPD patients on long-term ERT.1 After only a two-dose loading regimen in seven patients (two patients were enrolled prior to implementation of FVC monitoring), investigators observed an overall mean improvement in FVC of approximately 2.5% at 5 months as compared to baseline. Additionally, patients with moderate and severe LOPD exhibited a more substantial improvement in FVC, suggesting a rapid functional response. In addition to FVC, the study assessed the drug’s effect on exploratory biomarkers creatine kinase (CK, a biomarker for muscle damage) and urinary Hex4 (glucose tetrasaccharide, or Glc4, a measure of overall glycogen load) at Week 10. In a majority of patients, these biomarkers showed a reduction versus baseline at Week 10, consistent with the GYS1 mRNA knockdown and potential functional benefits. ABX1100 was well tolerated in the patients with LOPD, who experienced no infusion reactions, no serious adverse events, no treatment discontinuations, and no clinically meaningful laboratory abnormalities, including anemia, throughout the study. “This study provides clinical proof of concept for the use of RNA-based substrate reduction therapy to treat late-onset Pompe disease, representing the first time an siRNA therapy has been clinically evaluated in a lysosomal storage disorder," commented lead investigator Ozlem Goker-Alpan, M.D., president of the Lysosomal and Rare Disorders Research and Treatment Center in Fairfax, Va. "The impressive GYS1 mRNA knockdown data, along with the favorable safety profile and encouraging biomarker reductions, help us further characterize ABX1100 as a potentially promising addition or alternative to ERT in patients with LOPD. The early signals observed in forced vital capacity, while preliminary and based on a limited follow-up period, are also noteworthy and warrant confirmation in a larger, longer-duration study." “The robust GYS1 mRNA knockdown is quite striking, as is the efficacy on lung function and LOPD biomarkers observed after the administration of just a two-dose loading regimen,” added Dr. Sarma. “In particular, the improvement in forced vital capacity – an approved endpoint in other LOPD registrational trials – will guide our discussions with regulatory authorities as we explore how to rapidly move this first-in-class therapy into registrational development.” More information about the Phase 1b portion of the ABX1100 clinical trial is available at ClinicalTrials.gov, using the ID no. NCT06109948. About ABX1100 ABX1100, an investigational treatment for Pompe disease, is comprised of a CD71 receptor-binding Centyrin conjugated to a short-interfering RNA (siRNA) that specifically interferes with expression of GYS1 messenger RNA (mRNA), thereby reducing levels and overall activity of GYS1, the enzyme responsible for glycogen production, in muscle tissues. ABX1100 has received Orphan Drug Designation and Rare Pediatric Disease status from the United States Food and Drug Administration. About Pompe Disease Pompe disease is a rare neuromuscular disorder caused by a genetic deficiency of the enzyme acid alpha-glucosidase (GAA), which leads to a toxic buildup of glycogen in the muscle. This buildup leads to progressive loss of muscle function, weakness, and disability that can eventually progress to death from respiratory failure.2 Late-onset Pompe disease (LOPD) is a subtype of Pompe that has onset after the first year of life. The current standard of care for LOPD is enzyme replacement therapy (ERT), which aims to restore genetically deficient enzymes. Despite the availability of ERT, significant unmet need remains due to limited ERT efficacy and burden of care. ERT requires intravenous infusions that can last as long as 6 hours, multiple times a month. About Aro Biotherapeutics Aro Biotherapeutics is a biotechnology company working to develop potent and versatile tissue-targeted short-interfering RNA (siRNA) medicines for the treatment of immune-mediated diseases and diseases with high unmet medical need. The company is developing a wholly owned pipeline of therapeutic candidates for a diverse set of diseases, employing a proprietary protein technology called Centyrins, which are small proteins engineered for exceptional efficiency, versatility, and safety. For more information, visit https://www.AroBiotx.com/. Reference Berger KI, Chien YH, Dubrovsky A, et al. Changes in forced vital capacity over ≤13 years among patients with late-onset Pompe disease treated with alglucosidase alfa: new modeling of real-world data from the Pompe Registry. J Neurol. 2024; 271(8): 5433-5446. Pompe disease. MedlinePlus. U.S. Department of Health and Human Services, National Institutes of Health, National Library of Medicine; 2016. https://medlineplus.gov/genetics/condition/pompe-disease/ . Accessed January 29, 2026.