Summarizing key points from a recent webinar, we highlight five ways biomarkers and bioassays are set to change the clinical game. Learn how these translational research tools are helping improve clinical trial design and transform patient care.
As the science driving novel therapeutics charges forward, translational researchers are busier than ever creating new tools to link this exciting progress to patients. One way the translational medicine community is helping to bring groundbreaking discoveries to the clinic with more efficiency is through the creation of reliable, robust, and informative bioassays.
Translational researchers are developing bioassays to advance nearly every stage of drug development and delivery, from research to industry and clinical practice. Biomarker data can help increase our understanding of disease progression and response, refine treatment protocols, support more robust clinical trials, and streamline operations.
During a recent Cell & Gene webinar, Gregory Opiteck, PhD, VP Head of Translational Sciences at Allogene Therapeutics, and Douglas Sanders, PhD, VP Head of Translational Medicine at AVROBIO, shared insights into how translational bioassay advancements are helping to move the needle in favor of those fighting deadly diseases. In case you missed it, here are five ways they see biomarkers changing the clinical game.
1. Provide earlier insight into therapeutic efficacy to succeed and fail faster
With the right biomarker, incorporating bioassays into clinical trial design can help move clinical research forward faster ― a win for both drug developers and patients. "If you have a really strong biomarker that’s very well established as being predictive of clinical benefit, you can often use that biomarker to get an earlier approval," Sanders explained. Particularly in studies where disease progression is very slow and other indicators of efficacy may take a long time to signal improvement, reliable biomarker endpoints can make or break a trial.
Even if biomarkers don’t lead to earlier approval, they can still add insight to clinical research by allowing drug developers to ensure they are allocating resources to the right places. "Having those biomarkers as an early indicator of whether your drug is working appropriately in patients can be invaluable because if you’re going to fail, you want to fail fast," Sanders said. "And if you’re succeeding, you want to know that early on, so you know to keep putting resources into the development of that particular drug."
2. Identify patients who will respond to treatment to improve outcomes and trial design
As a companion diagnostic, biomarkers can allow investigators to recruit a suitable patient population that’s more likely to benefit from treatment. "If you can identify biomarkers in those patients that predict response to the drug, you can then select patients that are appropriate for your trial and have a much better chance of getting approval for a drug in a smaller patient population," says Opiteck. This targeting can make a big difference in detecting treatment effects of therapies for rare diseases, where large populations of patients may not be available to participate in clinical trials.
Beyond research and regulatory approval, companion diagnostics continue to offer benefit in the clinic by ensuring patients receive the most appropriate therapeutic option. These tests can help avoid the costs, treatment delays, and unnecessary side effects that come with giving a person with a drug that is not likely to work.
3. Drive composite endpoints for better powered studies
A multidomain responder index (MDRI) consists of multiple endpoints in one to capture an overall picture of how a patient or population is doing. "When you have complex diseases, especially where there’s a lot of heterogeneity in the patient population, any one of those characteristics that’s within the index may not necessarily show progress for that particular patient," explains Sanders. "Maybe other indicators would change in that patient whereas, in another patient, the set of indicators that show benefit from the drug are completely different."
Using biomarkers as part of MDRIs in clinical trials can help deliver more robust efficacy data for rare disease trials, where powering the study would be nearly impossible with a single indicator and a small number of patients. "If you use the MDRI strategy, you can potentially get more of a picture that, yes, maybe all patients aren’t moving toward efficacy in every one of these domains, but all of the patients are making progress in some of the domains," said Sanders. "I think that’s really exciting because it opens up the possibility that companies could actually get drugs approved for these ultra-rare diseases that really can only benefit from cell and gene therapy."
4. Offer a more cost-effective, efficient way of monitoring disease
In cancer, the standard of care to assess residual disease activity is PET scans. Due to high-tech equipment, the need for specialized imaging facilities, and a range of radiology costs, PET scans are expensive and can be logistically complicated. Moving toward minimum residual disease (MRD) bioassays would not only help reduce healthcare system costs, it could also make follow-up testing more convenient. Patients could simply go to a local clinic for a quick blood draw to determine if their treatment has worked.
But getting MRD assays qualified to use in place of PET scans is an ongoing challenge, for a variety of reasons. "I think that gets to some of the regulatory barriers but also just in the way medical schools train oncologists," Opiteck explained. "They train them on PET scans. Why? Because that’s standard of care. They don’t train on MRD. Why? Because that’s not the standard of care. And that’s the real intersection between real clinical practice in the world we live in and the clinical practice envisioned by key opinion leaders."
5. Bust silos in pharma with a single source of truth
Within a large organization, the traditional way of managing bioassay development is for preclinical, translational, and clinical assay work to happen separately from analytical assay development for product characterization. Opiteck emphasized the value of using a single bioassay as a source of truth. Having everyone speak the same language and make decisions based on the same validated tools helps to streamline the complex process of moving a drug through the pipeline. "We in translational can leverage a lot of the foundational work they do and then deploy that on the blood samples we collect in the course of our clinical studies," he shared as an example.
Then the question becomes, where does that assay live? Sanders says one possible solution is to have a centralized analytical development group. "It provides for a pool of people that have a very good understanding of all of the assays that are being used to support the development of the drug," Sanders said. "You have internal experts that can troubleshoot different aspects of those assays. And it also sort of forces at least one group of people to make the connection between the manufacturing assays and the preclinical and translational assays, and having that connection really helps to bridge the gap and can make sure that those groups are communicating appropriately."
If you’re interested in hearing more great insights from these translational experts, you can watch the webinar, Evaluating Translational Research Tools For CGTs, in full on demand here.
And for more information on how Cytiva can support your work in translational research, visit our webpage.