If 2024 was the year medicine proved that steady, methodical progress could deliver profound impact without spectacle, 2025 is the year those advances began to compound, converge, and translate into unmistakable clinical consequence.
Many of the defining breakthroughs of 2025 did not emerge in isolation. Instead, they represent the maturation of trends already visible last year: drug repurposing moving faster than drug discovery, immune engineering expanding beyond cancer, obesity medicines revealing both their power and their limits, and rare disease research pushing decisively toward precision and personalization.
Rare disease once again functioned as the early proving ground for approaches that are now beginning to influence broader clinical practice.
For those developing, evaluating, or delivering therapies, the lesson of 2025 is clear: rare disease is no longer peripheral – it is directional.
Rare Disease First: From Precision to Personalization
In 2025, rare-disease innovation moved beyond precision toward true personalization, with implications for both clinical pathways and development strategy.
The approval of elamipretide (Forzinity) for Barth syndrome marked the first disease-specific therapy for this mitochondrial disorder, validating decades of work in mitochondrial biology and highlighting the importance of mechanistic clarity in small populations. As Dr. Barry Byrne, Director of the Powell Gene Therapy Center at the University of Florida, noted:
“This is not incremental progress. It fundamentally changes the trajectory of what families can realistically hope for.”
Similarly, uniQure’s AMT-130, a gene-targeted therapy for Huntington’s disease, reinforced a growing conviction that disease-modifying approaches in neurodegeneration may meaningfully alter disease course rather than merely delay decline. As neurologist Dr. Zachary Simmons observed:
“The ambition has shifted from managing symptoms to changing biology.”
That ambition reached its most tangible expression in the case of baby KJ, who received the first-ever personalized CRISPR-based therapy for severe CPS1 deficiency. Designed, manufactured, and delivered for a single patient, the intervention demonstrated that bespoke gene editing can now operate on clinically relevant timelines. Reflecting on the case, physician-scientist Dr. Kiran Musunuru commented:
“Individualized genome editing is no longer theoretical. It represents a new model for treating ultra-rare disease.”
From a market research standpoint, this case is as significant operationally as it is scientifically: it challenges assumptions about scalability, regulatory engagement, and value frameworks in ultra-rare disease indications.
Importantly, 2025 also demonstrated that rare-disease innovation is no longer confined to commercial pharma. The FDA approval of Waskyra, forwarded by the non-profit The Telethon Foundation to treat Wiskott–Aldrich syndrome, marked a rare but meaningful moment for mission-driven drug development. The approval validated not only the therapeutic approach for this complex immune disorder, but also the growing role of non-profit organisations in advancing high-risk, low-commercial-incentive programmes through to regulatory success. It reinforced a central theme of rare disease: when scientific clarity and patient need align, innovation can emerge from outside traditional industry models.
Re-examining Assets: Wilson Disease and the Value of Persistence
Rare disease progress in 2025 also underscored the importance of revisiting undervalued or discontinued assets.
Monopar Therapeutics’ acquisition and reassessment of ALXN1840 (bis-choline tetrathiomolybdate) for Wilson disease exemplifies a growing recognition that rare-disease drug development is often non-linear. Despite strong mechanistic rationale, many assets falter due to trial design constraints, endpoint selection, or tolerability trade-offs rather than lack of efficacy.
Dr. Michael Schilsky, a leading hepatologist and Wilson disease expert, noted:
“Wilson disease has long suffered from a shortage of well-tolerated, targeted therapies. Re-evaluating ALXN1840 reflects a more mature understanding of how to assess benefit–risk in rare metabolic disorders.”
For developers, this signals a broader shift: persistence and fit-for-purpose development strategies may be as important as novelty.
Repurposing with Intent: Lessons Beyond Rare Disease
The strategic repurposing seen across many fields in 2025 mirrors approaches long familiar in the rare disease sphere.
The expansion of omalizumab into food allergy management reframed care from avoidance to risk mitigation. Resmetirom’s progress in MASH reinforced the value of metabolic pathway targeting across interconnected diseases. In psychiatry, lumateperone’s expansion into depression continued the move away from traditional monoaminergic frameworks.
Across these examples and other expansions, a consistent theme emerges: when disease biology is well-characterized, repurposing can accelerate access, reduce risk, and expand impact. These are principles that rare-disease development has relied on for years.
Platform Technologies Cross Disease Boundaries
In 2025, platform technologies continued to migrate outward from their original indications.
CAR-T therapies entered early clinical use in severe autoimmune disease, reframing treatment goals from chronic suppression to immune reset. In HIV, many small scale studies using a wide range of techniques – stem cells, broadly neutralizing antibodies (bNAbs), mRNA technologies, and gene therapy advances – have started to report functional cures, defined as sustained viral suppression following interventional treatment. These results suggest that durable HIV control may be achievable without continuous antiretroviral therapy, aligning with similar ambitions in autoimmune disease and metabolic disease.
For clinicians and developers alike, these shifts reinforce a critical insight: therapeutic platforms, not individual indications, increasingly define innovation trajectories.
Emerging Signals: Dementia, Infection, and Antimicrobial Renewal
Despite limited progress in disease-modifying dementia therapies, 2025 produced intriguing research signals. The strong evidence that some forms of dementia may arise from a convergence of herpes simplex infection and repeated head trauma reframed neurodegeneration as, at least in part, an acquired inflammatory process. Observational data indicating that shingles vaccination may reduce dementia risk further highlighted prevention as a potentially underappreciated lever.
In parallel, infectious disease delivered one of the year’s most quietly consequential breakthroughs. After decades of stagnation in antibacterial development, two novel antibiotics – zoliflodacin (Nuzolvence) and gepotidacin (Blujepa) – were advanced as effective treatments against increasingly drug-resistant Neisseria gonorrhoeae. Their success represents more than new options for a single sexually transmitted infection; it signals that rational antibiotic innovation, grounded in new mechanisms of action, remains possible even in areas long written off as commercially and scientifically exhausted.
For rare-disease researchers, these developments echo a familiar lesson: understanding the upstream mechanisms – whether genetic, immunologic, or microbial – often opens unexpected therapeutic and preventative pathways.
Obesity and Stewardship: A Cautionary Parallel
GLP-1–based obesity therapies provided one of the clearest reminders of why rare-disease thinking matters.
While highly effective, broader use of these therapies revealed trade-offs, including but not limited to loss of lean muscle mass, pancreatitis, gallbladder disease, ocular complications, and thyroid complications. These side effects are an especial concern as treatments beginning to transition from weekly injectable formulations toward daily oral obesity medicines and underscore the need for careful patient selection, sustained follow-up, and active stewardship.
These dynamics mirror long-standing realities in rare disease, where benefit–risk assessment, heterogeneity, and long-term follow-up are central to care.
What 2025 Tells Us
From our perspective as a medical market research team focused on rare diseases, 2025 reinforced several enduring truths:
• Rare disease remains the testing ground for precision, personalization, and platform innovation
• Repurposing and reassessment are not compromises, but strategic tools
• Clinical maturity increasingly matters as much as scientific novelty
• The lessons learned in small populations can inform broader care
For pharma, clinicians, researchers, and patients alike, rare disease is no longer simply a specialized domain: it is where the future of medicine is already being practiced.
By Leigh Hart, Senior Moderator at LDA Research
