While traditional medicines have, without a doubt, improved the lives of billions of people around the world, there are many diseases for which these traditional approaches can only modulate the rate of disease or mitigate disease symptoms without offering a cure.  However, what was previously seen as the ‘future of pharma’ for many years, cell and gene therapies (C&GTs) are now coming of age. These therapies are shaping an inflection point in our abilities to reverse disease progression by regenerating healthy tissue or by enabling cells to function in new ways by insertion of a gene. In some situations, this will enable us to treat and cure the formerly incurable, representing some of the most revolutionary innovations in patient care to date. Cell and gene therapies symbolize a new era of medicine, one which uses the body’s cells and genetic information to fight devastating conditions for which traditional small molecule therapies have previously fallen short, ranging from rare genetic disorders to more common conditions such as Parkinson’s disease and heart failure. Moreover, cell therapies in oncology are making great strides with ongoing innovation expected to increase the number of cancer patients who can benefit. So, how are these therapies different from traditional medicines? What sets them apart from everything that has come before? And what are the implications for pharmacovigilance and patient safety?


Cell therapy and gene therapy are fields of biomedical research and treatment, both aiming to treat, prevent, or potentially cure diseases. The key difference between cell therapy and gene therapy is that the former involves transferring intact living cells, originating either from the patient (autologous) or from a donor (allogenic) to help lessen, or even cure, a disease by restoring or altering certain sets of cells. These cells can regenerate new healthy tissue in a targeted area or, in the case of oncology, can be programmed to target and kill specific tumour cells. In contrast, gene therapy involves introducing, removing, or changing genetic information within a particular cell type. For genetic diseases such as Hemophilia or sickle cell disease, where patients inherit a deficient gene impacting protein production, for example, clotting factors or enzymes, restoring production and function of the normal protein can cure the disease potentially for the patient’s whole life.  In other diseases such as heart failure, gene therapy can have a targeted biological effect in the heart cells resulting in a major improvement in the patients’ cardiac function enabling them to perform activities not previously possible.


Given that C&GT products are substantially different from traditional medicines in their design and manufacturing, we have had to adapt our PV processes and activities in several crucial ways


The therapies at this new frontier of medicine are complex treatments that differ from traditional medications, both in how they are manufactured and administered, as well as the benefits they provide. Cell and gene therapies are a form of personalized medicine. Each is tailored to detailed information about the genesis of a patient’s condition to treat it at its source. In contrast, small molecules in traditional medicines act at a different level and do not aim to correct genetic deficiencies or replace dysfunctional tissue. Secondly, small molecules tend to act for a limited time, whereas gene therapy aims to insert the genetic material into the target tissue for extended periods.


These innovations are transforming healthcare at an unprecedented pace, presenting unique challenges for the investigators and companies pioneering this research. As with all therapies, it is key to ensure the safe and appropriate research and development of the C&GT pipeline. So, while we explore and advance C&GTs, Pharmacovigilance (PV) remains a critical partner in developing and executing these projects, monitoring safety profiles and conducting risk-benefit assessments throughout the product lifecycle.  However, given that C&GT products are substantially different from traditional medicines in their design and manufacturing, we have had to adapt our PV processes and activities in several crucial ways.


First, we have increased the level of communication between functional areas, medical societies, and patient advocacy groups for rare diseases, to encourage discussions regarding the potential benefits and risks of C&GTs, from design concept through to manufacturing. By closely collaborating across stakeholders, we can identify and apply the most innovative methodology and data-led decision-making to address questions and challenges. Further, given that C&GTs are emerging technologies, we cannot utilize the same well-established processes as we do for traditional medicines. So, we must place greater importance and scrutiny on preclinical models and subsequent clinical development of C&GTs.


We also have to modify our processes for identifying expected adverse events and benefit-risk profiling. Due to the precise nature of C&GTs, most potential adverse drug reactions are related to the therapy’s target tissue and can, therefore, be carefully anticipated and planned for. This means monitoring of patients in clinical trials becomes more focused, looking for the anticipated potential risks, as opposed to chemical medicines, where “off-target” risks can be more challenging to predict.


Lastly, although the standard processes for safety monitoring and reporting apply to C&GTs, longer-term observations of patients may be necessary during and after completion of clinical trials. Due to the relative scarcity of information about new uses of C&GTs, a cautious approach is usually taken, which can result in slower trial progress. So, a single patient may be given a dose of a C&GT, then followed for some time with the data reviewed by an independent Data Safety Monitoring Committee (DSMC). If no significant risks are observed, another patient is given a dose. As more experience accrues, the DSMC reviews the progress at the end of each dosing group. As always, patient safety is of utmost importance, so if any significant adverse events occur at any time during the study, they are reviewed promptly by the DSMC in addition to regular review by the sponsor of the study, and appropriate actions are taken immediately.


As well as the pressure of keeping up with the rapidly evolving science of C&GTs, it is an ongoing challenge to find the skills relevant to these newer areas. As is often the case, in a highly specialized environment which is innovating at rapid fire pace, the talent demand for qualified and experienced C&GT professionals may outweigh the supply. So as well as looking to strengthen internal C&GT capabilities, pharma companies are pursuing a large number of external collaborations, technology acquisitions and licensing to combine the best in Biotech and Pharma expertise to drive value in the highly dynamic and competitive industry of C&GTs.


Together with our partners, we want to expedite innovation at its source and along the whole value chain to bring these breakthrough therapies to patients who have no time to wait. By evolving our PV processes to collect safety information on C&GTs and taking action in response to potential risks, we are committed to safeguarding patient safety in this new era of medicine, throughout the lifecycle of our portfolio products.