Rethinking drug approval for ultra-rare disease: Inside the UK’s n-of-1 ASO trial
Last week, the rare disease field celebrated another breakthrough. A teenage girl with an ultra-rare genetic neurodegenerative disease was treated with a bespoke antisense oligonucleotide (ASO) at the Great Ormond Street Hospital (GOSH) in the UK. Nine other children with similar diseases will also be treated with a customized ASO therapy as part of the same trial, sponsored by EveryONE Medicines and approved by the Medicines and Healthcare products Regulatory Agency (MHRA).
EveryONE Medicines’ mission
EveryONE Medicines is a biotech company focused on developing n-of-1 therapies for patients with ultra-rare genetic diseases. The company was founded by Julia Vitarello after the devastating loss of her daughter Mila. A custom ASO (milasen) was created to treat 6-year old Mila, who had a rare genetic disease (Batten’s disease). Within one year of identifying the genetic mutation, the team at Boston Children’s Hospital - led by Timothy Yu - administered milasen. Unfortunately, while she experienced a short period of symptom alleviation after receiving the ASO, the disease had reached an advanced stage and she passed away.
In the wake of the loss of her daughter, Julia Vitarello decided to help prevent similar tragedies by increasing accessibility and scalability of n-of-1 therapies. EveryONE Medicines aims to develop an ASO library and push for suitable regulatory pathways for this approach. The impact of their efforts is starting to materialize, changing the lives of several children and their families.
The shift towards master protocol trials
The UK has become a practical place to test innovative genetic therapies. National genomic sequencing programs are identifying increasing numbers of children with rare genetic diseases, creating a clearer pool of patients in need of treatment. In parallel, regulatory and academic initiatives have begun to establish pathways for developing custom therapies. Together, these factors support the development and delivery of n-of-1 treatments.
The trial reflects a broader shift toward master protocol designs for individualized therapies. Instead of evaluating each bespoke ASO as a separate product, the MHRA has approved a single framework that standardizes how these therapies are developed and assessed. The focus is on validating the process used to create the drug, rather than the specific sequence administered to any one patient.
The protocol sets shared requirements for data collection, safety monitoring, and pharmacokinetic analysis, and applies to fatal or life-threatening neurodegenerative conditions. It relies on a well-characterized ASO structure that can be modified with limited changes for different genetic targets. Because one-off therapies cannot be evaluated through conventional randomized trials, the regulatory approach emphasizes close monitoring before and after treatment. If successful, it could establish a precedent for approving other individualized therapies based on a defined development process.
Similar thinking is beginning to take shape in the US. In November 2025, the FDA proposed the Plausible Mechanism Pathway for individualized therapies, outlining a potential route to approval for interventions that directly target a molecular or genetic aberration where trial enrollment is not feasible. The pathway reflects a growing willingness among regulators to consider strong mechanistic reasoning in place of conventional trials.
How platform approvals can revolutionize drug development
Rare disease drug development is severely limited by a lack of commercial viability. However, platform or process-based approvals have the potential to change the economics of individualized drug development. By standardizing how custom therapies are designed and manufactured, development timelines could be shortened substantially and costs reduced to levels that make broader access feasible. Lower costs would also make it more realistic for public health systems to engage with n-of-1 therapies over time.
Until now, there has been little structural incentive for companies to pursue individualized medicines. Developing a one-off therapy requires many of the same regulatory and manufacturing steps as a conventional drug, without the scale needed to justify the investment. As a result, only a small number of customized treatments for rare diseases have been developed in recent years, often supported directly by families rather than healthcare systems.
If the current trial is successful, this approach would allow variants of the same underlying molecule to be produced for other eligible patients without restarting the approval process each time. For children facing progressive and life-threatening neurodegeneration, the alternative to treatment is continued decline. In the absence of safer or established options, process-based approval offers a way to act responsibly while continuing to learn from each case.
Conclusion
Taken together, these developments point to a promising shift in how ultra-rare diseases may be addressed. For regulators, master protocols and process-based approvals offer a way to balance scientific rigor with clinical urgency. For sponsors, they create a more viable path to developing individualized therapies without starting from scratch each time. Most importantly, for patients and families who have historically faced diagnosis without options, they signal a future in which treatment is increasingly built into the system. While still early, this approach suggests that n-of-1 therapies can move from isolated acts of innovation toward a more sustainable and reproducible model of care.
Sano Genetics is supporting EveryONE Medicines by providing the digital and operational infrastructure that enables efficient execution of the UK trial. This includes strategy and implementation of a tailored participant experience, custom consent and screening workflows, streamlined at-home genetic testing, and secure systems that allow the EveryONE Medicines team to review genetic reports and manage cohorts in real time. These capabilities help operationalize an innovative regulatory framework into a trial that is reliable and scalable, helping EveryONE Medicines focus on the scientific and clinical strategy underpinning the program.