![](https://www.worldpharmatoday.com/images/nBanners/Docuvera-728x90.jpeg")
It is a well-established fact that gene therapy research happens to be booming. Since the U.S. Food and Drug Administration- FDA issued its first approval when it comes to gene therapy in 2017, oncology researchers have gone on to be breaking barriers as far as gene therapy trials are concerned, which was then followed by an explosion in mRNA research throughout the COVID pandemic.
In today’s times, this trailblazing science happens to be providing new ways to go ahead and approach rare diseases and, at the same time, a new hope when other investigational interventions have gone on to fail. As a matter of fact, the majority of approved gene therapies happen to be for rare diseases. To be exact, 14 are currently in Phase III trials for 10 rare diseases, and 45 gene therapies happen to be in the early stages of development in order to treat 30 rare diseases.
According to the senior vice president of biotech delivery at Parexel, Leslie Johnston, they see great potential when it comes to gene therapies since more products have been approved, and the fact is that it will gain traction with more companies looking to expand their therapies within other therapeutic indications. This progress goes on to present a tremendous potential to change even more patients’ lives across several varied diseases.
This can as well be a gene therapy’s moment. But so as to fully make use of it, the industry must clear some really intricate hurdles. Gene therapies happen to pose several unique challenges when it comes to clinical research, such as ethical and safety considerations, precarious logistics, regulatory hurdles, and potentially staggering costs. These challenges may as well have many ramifications, such as the fact that the number of New U.S. patients treated via gene therapies approved or in development is anticipated to fall by one-third from 2025 to 2034.
So what’s the way forward when it comes to clearing these hurdles? Cooperation between sponsors, patients, sites, regulators, and other stakeholders happens to be essential to expediting advancement when it comes to life-saving gene therapies.
Regulators should go on to address risks sans limiting innovation
Gene therapy trials happen to be strictly regulated, and rightly so due to the novel nature of the intervention as well as the potential long-term consequences. Gene therapy interventions also happen to carry inherent safety risks, such as the potential for unintended genetic changes or even adverse immune reactions. Making sure of patient safety happens to require rigorous monitoring as well as adherence to stringent protocols.
But getting regulatory approval under such conditions happens to be time consuming as well as resource intensive. In order to avoid hampering scientific growth, regulators should look forward to ensuring that the requirements happen to be appropriately rigorous sans being unmanageably onerous.
Thankfully, the FDA happens to be paying close attention to gene therapy and has gone on to demonstrate a desire to go ahead and work with drug developers when it comes to the success as well as the approval of these treatments. The Director of the Center for Biologics Evaluation and Research- CBER, at the FDA, Dr. Peter Marks, has gone on to express his hope for an exponential, if not logarithmic, surge when it comes to gene therapy approvals.
He adds that there is indeed immense excitement that this can go on to potentially make a big difference when it comes to the treatment of human disease.
The fact is that the FDA is going beyond mere rhapsodizing as well as taking action to speed up gene therapy. In 2023, the agency went ahead and launched a pilot program known as Support for Clinical Trials Advancing Rare Disease Therapeutics- START which happens to be designed to speed-up the development as well as the approval process in terms of treatments targeting rare diseases by way of providing regulatory guidance, assistance, and incentives to sponsors who happen to be conducting the clinical trials in this field. The program goes on to represent quite an important step forward in terms of fostering innovation as well as collaboration between the regulatory bodies and, of course, the sponsors.
Apart from this, the FDA happens to be working to go ahead and harmonize global requirements when it comes to the review of gene therapies. Encouraging as well as facilitating international cooperation, along with the harmonization of regulatory standards, such as mutual recognition agreements and shared regulatory pathways for multinational clinical trials, can go on to help streamline gene therapy development across the world and help in getting the innovations to patients at a faster rate.
Even with this kind of growth, regulators should continue to help speed up gene therapy research by streamlining regulatory pathways specifically customized to gene therapies. This means offering clear guidance on the needs for preclinical as well as clinical development, fostering collaboration when it comes to stakeholders so as to share knowledge and best practices, and also offering some fast review processes in terms of gene therapy products that are aimed at treating serious or even life-threatening diseases.
With a whopping 2,500 cell and gene therapy investigational new drug application- INDs on file, the FDA happened to approve only five cell and gene therapies in 2023. Dr. Marks has gone on to suggest that accelerated okays, which have successfully developed advanced cancer and HIV/AIDS treatments, may as well be the most appropriate path for such a new category of treatments. But regulators are also required to commit to proactively partnering with the developers so as to understand the patient population as well as the risks and benefits of every new therapy.
Likewise, researchers, industry stakeholders, and patient advocacy groups should also go ahead and engage with regulators in order to help them understand the unique issues and opportunities within the field of gene therapy. This can help the regulators adapt regulatory frameworks so as to ensure patient safety while at the same time expediting the development and approval of promising treatments.
Sites as well as sponsors must be prepared
Of course, sites as well as sponsors also happen to have a crucial role to play when it comes to advancing this promising field of medicine. Clinical trial sites should go on to enhance their capacity so as to conduct gene therapy trials safely as well as effectively, and sponsors should do their part so as to assist sites in these efforts.
By way of working closely with the clinicians as well as the regulators, sponsors can go on to make sure that the trial development process goes on to sync with clinical needs as well as regulatory standards. Sponsors should indeed have a thorough understanding of FDA needs pertaining to design, preclinical testing, and long-term follow-up. Better syncing from the outset will go on to lead to more efficient trial designs, better and faster regulatory approvals, and, hence, ultimately, quicker patient access to therapies.
For instance, sponsors working with mRNA as well as other genetically engineered therapies across North America not only have to go via the institutional review board- IRB review, but they also have to go ahead and navigate additional requirements coming from the U.S. National Institutes of Health- NIH Office of Science Policy Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules- NIH Guidelines. These requirements usually happen to involve an additional biosafety risk evaluation review coming from an institutional biosafety committee- IBC in addition to the IRB review.
NIH Guidelines go on to apply for any research that involves recombinant or synthetic nucleic acids, such as genetically engineered materials, that receives NIH support or takes place at sites that have already received NIH support for such a kind of research. Even when there happens to be zero NIH support, IBC review has gone on to be considered a best practice. IBC review as well as inspection help sites make sure that they are fully prepared by way of identifying areas when it comes to advanced biosafety protections and calling out gaps within the current standard operating procedures- SOPs. Proactive coordination as well as integration of such separate review processes can go on to speed-up the trial timelines and help the sponsors consistently go ahead and address any potential concerns or even issues.
Sites can be better prepared by pre-registering an IBC. The NIH goes on to take six to eight weeks or more so as to approve a new registration, apart from the IBC review time; hence, hence by way of registering an IBC before they even happen to have a trial, sites can go on to save a month or more when it comes to the startup time over a site that waited to register.
Clinical trial sites that are looking forward to host gene therapy studies must indeed be prepared in other ways, both in terms of knowledge and infrastructure. Gene therapy studies go on to require specialized infrastructure when it comes to manufacturing, storing, and administering genetic material so as to adhere to strict biosafety guidelines. Probably something as simple as having an upholstered chair in the infusion room, which would pose an unacceptable contamination risk if the genetic materials were to spill, would then require the site so as to rethink its current processes. Rigorous training also holds the key due to the added risk when it comes to spreading genetic material to caregivers and others in close contact with the patients. Research staff apparently, must be specially trained so as to handle, deliver, and dispose of this material safely.
The fact is that these measures can indeed go on to seem intimidating for sites that happen to be already cost-constrained. Large academic medical centers with more resources and experience are more likely to be kind of well-positioned for such studies. For instance, they may as well have conducted bench, animal, and/or agricultural research in terms of genetic engineering or have funding so as to make any required adjustments, such as buying special equipment. However, to maximize the potential number of sites in which this research can be conducted and hence reach more potential participants, the sponsors might consider offering help in the form of financial assistance, SOP guidance, training curricula, and more to smaller sites that are looking to conduct gene therapy research.
It is well to be noted that the logistical complexities, depending on the investigational medicine as well as the therapeutic area, happen to be among the most complicated challenges when it comes to gene therapy trials, said Johnston. Right from collecting the specimen from the patient, altering or modifying it, storing it, transporting it, and even returning it back to the patient. all happen to come with a tremendously unique logistical hurdle and go on to need equally unique equipment, technology, and expertise. And it can also be cost-prohibitive.
Patients must be fully aboard
The most essential stakeholder in any clinical trial happens to be the patient. In gene therapy research, which can be especially demanding, patients must go on to have a complete understanding of as well as commitment to their involvement. Comprehending the potential risks as well as the benefits can go on to help patients come up with informed decisions and also navigate the study process.
Firstly, it is indeed crucial for patients to go ahead and adhere strictly to the protocol provided by the clinical trial team, like following medication schedules, maintaining particular hygiene practices, and, at the same time, attending all study visits. They should push to maintain optimal health in order to enhance the body’s response to gene therapy. And so as to avoid delays, patients should go ahead and maintain open as well as honest communication with the clinical trial team and go on to report any changes when it comes to the symptoms, side effects, or even the general health as soon as they go ahead and occur.
It is well to be noted that the trial participants also have to be in it for the long haul. Since the fact that gene therapy interventions look forward to producing lasting effects and cures, they typically need some long-term patient follow-up in order to evaluate efficacy as well as safety. But they may also require incredible patience.
Johnston went on to explain that there are several complexities that can go on to impact study progress. For instance, unpredictable logistical challenges such as a weather event or vehicle accident could as well go on to delay a temperature-sensitive delivery to a particular site, or data review outcomes can as well go on to need an indeterminate pause period. Patience as well as agility are indeed must-haves; however, it is indeed difficult for patients to potentially rely on this new therapy so as to save or change their lives.
Finally, the fact remains that industry cannot forget patients. Involving patients as well as patient advocacy groups within the regulatory process can go ahead and help to make sure that the development of gene therapies gets aligned with patient requirements and priorities, and it can also shed light on risk-benefit perspectives coming from a patient’s viewpoint. The more such perspectives are considered right from the start, the greater happens to be the chance of a trial’s success.
The co-founder of the Mighty Milo Foundation, Rita Naman, stresses the need for a more collaborative and patient-centered approach to gene therapy development.
For ultra-rare diseases such as SPAX5, gene therapy goes on to give a glimmer of hope where the traditional treatments do not. However, the logistical barriers go on to make these therapies expensive as well as inaccessible, says Naman. Tight collaboration with patients, industry, and regulators could go on to streamline such processes, bring costs down, and at the same time speed trials. Patients as well as their caregivers, along with the advocacy groups, should indeed be invited into the earliest discussions so as to prevent false starts or missed milestones within gene therapy development, specifically as the patient’s priorities do not always line up with those of the sponsor’s.
In the fight for gene therapy breakthroughs, cooperation happens to be the key
The road when it comes to operationalizing gene therapy clinical trials happens to be laced with land mines as well as potholes. So as to capture the overall potential of novel gene therapy research, new level of partnership between sponsors, CROs, sites, oversight committees, regulatory bodies as well as the patients is paramount.
As per Johnston, patients are looking to access novel gene treatments, and they need them fast. Sponsors are looking to deliver but have to fight against logistical and financial obstacles. Regulators are looking to ensure safety first, specifically considering such a new, promising science. These three objectives may go on to seem conflicting at times, and hence one needs to strike a balance when it comes to safety and speed so that the patients do not go on to miss their only probable treatment opportunity.
