New categories of emerging biologics and advances in cell and gene therapies are driving an evolutionary change in the contract research organization (CRO) industry as these companies adapt their organizations to supply the services needed today.
The rapid growth and uptake of technologies, such as CRISPR, CAR T cells, bispecifics and more, are significantly influencing the landscape of biotech and pharma drug development. To keep pace and provide the required support, CROs are investing in cutting-edge science and growing their service offerings to facilitate the field. GEN recently spoke with four market-leading CROs to get their insights on the current state of the industry and what the future holds.
“We are increasingly being asked to design developmental strategies for innovative products that are often ahead of the regulatory guidance documents. Previously, it was biotechs that commonly developed these products, but now the number of large pharmas asking for guidance and support is growing as they acquire or develop these state-of-the-art technologies,” states Pete Gaskin, PhD, senior director of scientific advisory services, Charles River Laboratories.
“The number of small virtual biotech companies is rising, and they are increasingly outsourcing work earlier and in an integrative fashion. We have over 5000 clients, many of which are small, virtual companies. We continue to adapt our organizational design to ensure we meet their needs. In this space, we see an expanding amount of customers who want to use a single source for discovery and safety assessment.”
According to Gaskin, Charles River is increasingly viewed as a partner not only at the technical level but also in strategic scientific support. This is driven partly by small virtual companies that do not have the expertise in house, and now partly by large pharma needing more support for innovative products.
“Compared with five years ago, we have seen small biotech companies become important contributors of the global biomedical innovation ecosystem and R&D pipelines. The infusion of funding for these companies is increasingly shaping the capability and capacity building at CROs in research, preclinical, and clinical stages,” says Edward Hu, co-chief executive officer, WuXi AppTec.
WuXi AppTec has also seen the rise of biotech companies focusing on cell and gene therapies, as well as other new modalities beyond the traditional “rule of five” chemistry space, for example, protein degraders, oligonucleotides, and peptides. The rapid advancement of basic and clinical science on cell and gene therapies has established a strong foundation for biotech companies to leverage.
“In addition, in emerging-market countries biopharmaceutical and biotech companies are beginning to contribute to the global R&D pipeline across the major disease areas through both internal R&D and in- and out-licensing partnerships,” continues Hu. “The rising standard of living, coupled with the unmet medical needs in these countries, is stimulating the growth of regional biopharma and biotech industries.”
Streamlining the process
Parexel Biotech has also seen a transition in the pipeline from the large pharmaceutical organizations that previously dominated biotech development to small- and mid-sized companies.
“[Every] company must have a strong development strategy to meet clinical development timelines; optimize product and pipeline value; and navigate competitive, regulatory, and reimbursement landscapes,” says James Anthony, senior vice president, global head, Parexel Biotech. “Elements such as synthetic control arms, online recruitment, eConsent, direct-to-patient drug shipments, patient apps, and video dosing are also becoming increasingly utilized. As an industry, improving the process for patients will help us streamline and overcome challenges to getting new therapies to market sooner.”
Instead of collecting data from patients recruited for a trial who have been assigned to the control or standard-of-care arm, synthetic control arms model those comparators using real-world data that has already been collected during routine care. Sources include electronic health records, administrative claims data, patient-generated data (from fitness trackers or home medical equipment), disease registries, and historical clinical trial data.
“I see the role of CROs building as they take on an even larger role in accelerating, guiding, and simplifying drug development,” adds Anthony. “Particularly in biotech, where expectations are high, resources are short, and timelines are aggressive.”
Emerging therapies are bringing a shift in the approach to clinical research and trials. “An increased focus on patient-centricity has been embraced by governmental agencies, patient advocacy groups, and industry. Not only is this important from the ethical standpoint, it is also pragmatic. Patient-centricity ensures we design the right studies and engage patients early so they are more likely to want to participate as partners in the clinical trial process,” explains Monica Shah, MD, FACC, vice president and head, Cell and Gene Therapy Center of Excellence, IQVIA.
“A key trend in clinical research will be considering long-term follow-up approaches using innovative strategies such as decentralized virtual trials, which feature partnerships with primary healthcare providers (to decrease patient burden and increase efficiency, patient retention, and accessibility), digital technology and platforms, direct-to-patient services, and electronic health records.” Cell and gene therapy clinical research is complex. Highly qualified facilities and tools are needed, as are training and support resources, especially since many trials involve a specialized patient population, end-stage patients, or patients with rare diseases.
Trials require specific medical expertise, institutional infrastructure, sophisticated management resources to handle potential adverse effects, and the resources to retrieve and store the cells to manage the investigational products. Due to the current state of the technology, only a limited number of sites have all the capabilities in place.
For cell and gene therapies, Shah sees a need for increased training, upskilling, and certification of a broader group of investigators and sites. Creative approaches to manage the required long-term follow up, including decentralized trials, will be used more frequently. “Finally, I see a trend toward larger sample sizes, more complex Phase II and Phase III studies, and a greater move to apply these therapies to many different therapeutic areas, and both inherited and acquired diseases such as different types of solid tumors, Alzheimer’s disease, diabetes, and cardiovascular disease.” Shah concludes, “Strategies to enhance recruitment and retention of patients and support sites will be critical.”
To maximize results from interactions with CROs, the experts concur that a true partnership is critical. “Be open and honest with the CRO,” advises Gaskin. “We cannot design the best strategy unless we really understand the products and the work done to date and the rationale, the commercial approach, and level of acceptable risk.”
“If a company is developing advanced therapeutic products, partner with a CRO that has experience with the molecule or treatment modality,” Gaskin adds. “The right mindset requires experience from regularly working with these types of products. A deep understanding of the science is required to address the safety liabilities, which often require novel approaches to the design of the assessment program.”
“Work together as a partner from the very beginning. A CRO like IQVIA not only can provide excellent delivery services, but can help support strategic planning for clinical trials as well as commercialization planning,” says Shah. “In particular, we support embedding evidence-based and patient-centered approaches into cell and gene therapy clinical trials.”
According to Anthony, it is critical that in the earliest stages, companies consider their long-term development strategy, including clinical, regulatory, and reimbursement strategies. Marketing approval is no longer the only hurdle, and companies need to select a partner with expertise in areas that are critical to their success so they can get it right the first time and mitigate any unnecessary risk of delays or failure.
CRO Helps Small Companies with Small Molecules and Large Molecules as Well as with Cell and Gene Therapy Research
As the president and CEO of Absorption Systems, a preclinical CRO, Patrick Dentinger notes that clients have traditionally come to the company for help with their small-molecule programs, including studies in pharmacokinetics involving factors such as drug metabolism; transporter, ocular, and dermal efficacy; toxicity; and bioequivalence. “Over the past few years, we have experienced an explosion of work in the large molecule and cell and gene therapy areas, particularly potency and release testing,” he points out.
In the small-molecule space, one of the company’s most-leveraged technologies is IDAS2 (In vitro Dissolution Absorption System 2). “It enables dissolution and transepithelial permeability to be ascertained simultaneously,” Dentinger asserts. “While this unique capability is extremely important to our small-molecule clients, IDAS2 further allows us to evaluate the effects of variables such as particle size on permeation and absorption. The ability to generate all that information in one assay is a boon to the industry. As I mentioned earlier, cell and gene therapy companies have approached us to develop potency assays for their programs, based on our previous successful collaborations in this area. While many companies understand the science, they may not yet appreciate the complexities of the regulatory environment. This is where CDMOs and CROs, like Absorption Systems, can really help.”
According to Dentinger, all the studies the company conducts for clients are centered on the Scope of Work, which is a collaborative document about the parameters of the study and the methodologies employed. During the study, communication is essential, he emphasizes: “Absorption Systems strives to maintain an active communication with clients.” Other than that, there should be a mutual appreciation for the science, he says, meaning that given the technologies that are at the company’s disposal, Absorption Systems will follow the science and the data to its “natural and reasonable” conclusion.
“Very often, we are the experts in the services we provide, whereas the client has much more knowledge specific to their drug substance,” Dentinger tells GEN. “It is very helpful for both sides to appreciate the value the other party brings to the table. While each project is unique and may present its own challenges, working with CROs with a long history of success in the industry, like Absorption Systems, will help mitigate risk and reduce timelines for the client.”