My first project as a Medical Writer was a clinical trial report for a placebo-controlled study of an acne cream. A classic two-group study design of active versus placebo that you see very rarely in these days of adaptive, multi-part study designs. Written to the then newly released ICH E3 guidelines, there followed projects on a fibrin glue for liver resection and a strange bacterial toxin to relieve cervical dystonia soon to be more widely known as blockbuster beauty treatment Botox.
Some years later I started to hear about personalised medicine. The premise was to identify patient-specific issues and prescribe drugs to deal with each of them. I remember a colleague proudly listing the drugs he was taking to reduce his blood pressure, modify his dyslipidaemia and reduce his cholesterol.
Polypharmacy, as it later became known, was based on small molecules – but small molecules act broadly. They bind, block, activate, or modulate. Historically, they were administered to all patients irrespective of their response. The feeling was that if the molecule demonstrated efficacy across multiple clinical trials, it would work for every individual. But, even then, individual variation in responses to drugs were identified as a substantial clinical problem [1]. Genomics-driven profiling has since shown that many patients were exposed to small molecule treatments (and their potential adverse effects) with only a limited chance of benefit. For example, polymorphisms in the cytochrome P450 2D6 gene have shown that individual responses to many small molecules treating psychiatric, neurological, and cardiovascular diseases are unpredictable and side effects common.
I moved from a global CRO to a Big Pharma behemoth and from there to a new-start called Niche, second man in and a massive diversity in projects. Fast forward to 2012 and we were approached by a blue chip pharma company to work on a new experimental gene therapy to treat genetic disorders adenine deaminase severe combined immunodeficiency (ADA-SCID) and Wiskott Aldrich Syndrome (WAS). It was becoming apparent that with the advent of the new treatment paradigm personalised medicine was getting serious. Little did I know that we would be working on the design, structure and content of the first successful gene therapy submission, StrimvelisTM, the first gene therapy licenced in Europe in 2016. Targeting the gene responsible for the single enzyme deficiency that causes ADA-SCID, StrimvelisTM restores immune function in profoundly immunocompromised children.
Gene and cell therapies operate at a different level to small molecules, they intervene directly in the biological processes that define disease. They are the ultimate personalised, precision medicine, aimed like an arrow at the bullseye of a target.
But the frustration is always that the development and licencing of new therapies takes so long. The reason may be given by another project we supported, a gene therapy for Fabry disease. Despite considerable time and effort put into the programme, it was suspended to focus resources on another gene therapy the client were developing for Gaucher disease. Even the most promising therapies have to battle for resources in the economic reality of drug development.
These therapies are tailored, not mass‑produced. They are crafted, patient by patient. Each batch is unique. Each manufacturing run is effectively a clinical event. And each patient’s biology shapes the outcome. This level of personalisation and precision is something with which small molecules never had to contend. Its success is a testament to the depth of research and understanding that is required for new therapeutic modalities.
Innovation moves quickly
Gene and cell therapy science is evolving at breakneck speed. New vectors, promoters, conditioning regimens, and delivery technologies emerge constantly. Standards of care shift in real time and only agile teams can drive progress in development programmes.
Our small CRO has flourished in this environment and it has been tested since our first encounter with cell and gene therapies almost 15 years ago. We’ve supported projects advancing autologous gene therapies for rare immunodeficiencies [2], pioneering lentiviral approaches, complex cell‑based programmes, and arenavirus‑based immunotherapies for cancers and infectious diseases [3]. Each programme requires a different operational model, and the ability to pivot quickly as new data become available.
One of our founding tenets that has served us well over the last 25+ years has been to ensure that we had direct communications between our delivery teams and our clients. This ensures that decisions can be made quickly. Teams are cross‑functional and deeply experienced; processes are adaptable rather than rigid and quality is embedded in functionality. Our size, structure and internal communications ensure scientific dialogue is continuous, not siloed, it also gives us our agility and the ability to flex to client requirements.
This is where small CROs shine.
Different Patient Relationships
Patient engagement in clinical development has evolved over the past decades, with a crucial inflection point provided by the HIV/AIDS crisis of the 1980s [4]. Patients now routinely provide input on study direction and central research questions [5]. While patient voice is now considered important in small‑molecule trials; in gene and cell therapy trials, it is critical.
Patients and families are often highly informed, deeply motivated and active partners in decision‑making. For Fabry disease, patients bring decades of lived experience with enzyme replacement therapy and its limitations. Families are often strong advocates for trial access and transparency. Their insights shape endpoints, feasibility assessments, and risk–benefit discussions. A small CRO can build genuine relationships with patient communities, something large organisations struggle to do at scale.
Wiskott–Aldrich Syndrome is caused by a mutation in the WAS gene that disrupts immune function and platelet formation. The result was described to me as a ‘living hell’ for the young patients by a Doctor treating the disease [6]: repeated hospitalisations for severe episodes of thrush, pneumonia and bruising, and often rheumatoid arthritis, leukaemia or lymphoma. The great benefit of gene therapy is that it doesn’t just treat symptoms; it corrects the underlying defect by inserting a functional copy of the gene into a patient’s own stem cells [7,8]. It was our experience that families were willing to travel across continents to access trials. One anecdotal story is that of a family with a child suffering from a rare disease who flew from South America to Madrid, followed by a bus to Milan just to ask for access to a new rare disease gene therapy. The child was successfully treated. They made that journey fuelled by hope, with no guarantee of treatment.
Our journey with WAS started in 2012 coming to fruition in November 2025 with the successful MAA submission to the EMA closely followed by successful FDA registration the following month. Our final contribution over a decade or more spanned multiple sponsors and different levels of contribution.
Why small CROs are built for this future
Looking back we have been privileged to work on a broad range of projects from preclinical vector design through first‑in‑human trials, pivotal studies, and post‑marketing follow‑up. We’ve worked across immunology, metabolic disease, oncology, and rare genetic disorders. If there is anything I’ve learned, it’s that success in this field depends on being able to:
- Understand the science deeply
- Anticipate operational challenges
- Navigate evolving regulatory expectations
- Build trust with sponsors, investigators and patients
- Adapt quickly as data emerge
The fields of gene and cell therapy reward expertise over scale, agility over process, scientific literacy over sales pitches, volume and collaboration in contracting.
When working on a bivalent vector-based vaccine, we were faced with a highly charged, multi-disciplinary team eager to contribute to a host of submission documents. The experience of the team ranged from basic laboratory scientists familiar with the process of genetic modification but new to regulatory documents through to seasoned industry professionals. Our task was to translate their ‘enthusiastic’ contributions into a successful regulatory submission package. Our PhD scientists were able to talk the language of the different team members.
Success in this arena is dictated by who listens and who understands the client’s needs and puts them before contractual constraints. Giving yourself time to be scientifically engaged also helps. Caring is not always the first line for your bigger CROs.
Conclusion
As I approach 30 years in the industry I can’t help but feel very lucky. Lucky in the fantastic people I have had the opportunity to work with and lucky to work at the cutting edge of scientific discovery, always stimulating and challenging. Many people spend decades working somewhere along the drug development pathway and never achieve successful licensing. In contrast, I have been fortunate to see treatments I have worked on directly benefitting patients. Challenges await in the future, but ‘twas always thus. Identifying the direction of most rapid travel remains key and currently it appears to be deep scientific knowledge capable of flexing to the requirements of cell and gene therapies.
References
- Wolf CR, Smith G, Smith RL. Science, medicine, and the future: Pharmacogenetics. BMJ 2000;320:987–990
- Niche Science & Technology. Orchard Therapeutics plc – Case history [Internet]. Richmond (UK): Niche Science & Technology; 2025 [cited 2026 Feb 23].
- Niche Science & Technology. HOOKIPA Pharma – Case history [Internet]. Richmond (UK): Niche Science & Technology; 2025 [cited 2026 Feb 23].
- Hardman TC. The Evolution of Patient Voice [Internet]. Richmond (UK): Niche Science & Technology; 2023 [cited 2026 Feb 23].
- Hardman TC. A Visionary Role of Patient Involvement in RASP UK [Internet]. Richmond (UK): Niche Science & Technology; 2015 [cited 2026 Feb 23].
- Cook J. Deliverance [Internet]. LinkedIn; 25 Nov 2025 [cited 2026 Feb 23].
- Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, Callegaro L, et al. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. 2009;360:447–58
- Ferrua F, Cicalese MP, Galimberti S, Giannelli S, Dionisio F, Rolfe L, et al. Lentiviral haemopoietic stem-cell gene therapy in Wiskott-Aldrich syndrome: a long-term follow-up study. Nat Med. 2019;25(2):286–95.
