Sano blog

3 recent signals that hint at the next phase of rare disease development

Written by Sano Marketing Team | Nov 14, 2025 6:20:26 PM

Recent activity in the US and UK offers important signals for how personalized and rare disease therapies may evolve. Scientific teams are building structured editing platforms, regulators are considering new evidence models, and national systems are exploring flexible licensing approaches. Taken together, these shifts reflect growing recognition that traditional development and regulatory pathways cannot accommodate the rising number of gene-specific and variant-specific therapies. They point toward practical strategies that could make next-generation therapies more feasible to develop and deliver. This blog highlights three developments and what they could mean for future sustainability and commercial viability in precision medicine.

A platform approach to personalized gene editing treatments

After the groundbreaking success of developing a bespoke in vivo CRISPR therapy for baby KJ earlier this year, physician-scientists Kiran Musunuru and Rebecca Ahrens-Nicklas published their lessons from that case and plans for expanding access to more children. 

Their approach to gene editing treats individualized therapies as variations on a shared platform rather than isolated interventions. Their phenylketonuria (PKU) and urea cycle disorder (UCD) programs rely on small adjustments to guide RNAs or deaminase domains within consistent delivery and manufacturing systems. They referred to this platform approach as an “umbrella of umbrellas,” whereby the large umbrella is UCDs and each subtype (e.g., OTC deficiency, arginase deficiency) is a smaller umbrella with distinct genetic variants that will require variant-specific guide RNA and an amendment to the umbrella IND. 

The FDA’s feedback supports this direction. For PKU, the agency accepted a unified IND across six variants with limited toxicology and allowed new variants to be added with in vitro data. For UCDs, the FDA proposed coordinated gene-specific INDs anchored by one master protocol and a shared toxicology package. 

These interactions highlight a practical path for modular editing systems. Reuse of nonclinical data, aligned protocols, and a single toxicology foundation can help manage some of the regulatory and cost pressures that currently constrain personalized therapy development. Importantly, materials from their pre-IND interactions and the FDA’s responses are now available online. This level of transparency could help other groups understand what the FDA considers as acceptable evidence for early platform-based editing programs.

The UK is developing a regulatory framework designed for rare disease

On November 2nd, the UK’s Medicines & Healthcare products Regulatory Agency (MHRA) published a policy paper outlining an approach for small populations, variable products, and advanced modalities. A full draft of the framework is going to be published in Spring 2026.

The plan includes proportionate evidence models, structured use of prior knowledge, and investigative licensing that allows iterative assessment. The MHRA is also examining how natural history, real-world data, and platform-level CMC information can support regulatory decisions when conventional trials are difficult.

The proposal also aims to align the regulatory framework with existing healthcare pathways to maximize uptake. The plan will be supported by national registries and long-term monitoring. Flexible licensing structures may allow therapies with patient-specific elements to belong to a single authorization.

This work points to a system anticipating a higher volume of individualized therapies and preparing tools to manage them. Developers benefit from clearer expectations and more predictable evidence requirements, which are both essential for commercial planning.

The FDA is outlining a mechanism-based pathway for individualized therapies

In the New England Journal of Medicine, FDA leaders Vinay Prasad and Marty Makary describe a plausible mechanism pathway that would allow individualized therapies to advance when the biological target is well defined and early evidence shows the intended molecular effect.

The experience with baby KJ provides the model. The FDA relied on natural history to establish context, accepted mouse data showing on-target editing, and considered early clinical outcomes. The article also suggests that once a developer demonstrates consistent success across several individualized interventions, platform data could support additional approvals.

This mechanism-centered approach reflects the reality that traditional trial structures cannot scale to thousands of patient-specific variants. A pathway that recognizes platform performance and biological plausibility could make individualized therapies more practical to bring forward. Variant-specific therapies can progress with early molecular evidence rather than full clinical datasets.

What these signals mean for the field

These developments point to several themes:

  • Platform structures are becoming an anchor for rare disease development
  • Coordinated INDs, umbrella trials, and modular submissions enable reuse of nonclinical and CMC data, which can help manage cost and timelines.
  • Prior knowledge is gaining formal regulatory value
  • Natural history data, in vitro studies, shared toxicology, and cross-referenced dossiers are increasingly recognized as legitimate components of evidence packages for small populations.
  • Access and system alignment are being integrated earlier
  • New models incorporate national registries, long-term follow up, and coordination to support delivery and reimbursement where trial data will remain limited.
  • Post-market registries, long-term monitoring, and real-world evidence are increasingly expected to complement small, early trials, particularly for ultra-rare and variant-specific conditions.

A potential path toward more sustainable personalized therapy development

These signals suggest a shift toward frameworks that can support individualized and ultra-rare therapies at greater scale. These strategies may help reduce some of the regulatory and cost barriers that have historically limited access to personalized therapies. As these ideas evolve, they could lay the groundwork for a more sustainable and commercially viable era in precision and rare disease medicine. 

Sponsors that invest early in platform design, evidence generation, and patient access pathways will be better prepared to operate in this next phase of rare disease development.

To learn about how Sano Genetics can support gene therapy trials with precision recruitment and long-term participant engagement, read our case study.