The COVID-19 pandemic has increased the pace of drug development and regulatory approval dramatically, accelerating activities in ways that shorten the time needed to deliver safe, effective therapeutics, vaccines and diagnostics to patients.
The COVID-19 pandemic has increased the pace of drug development and regulatory approval dramatically, accelerating activities in ways that shorten the time needed to deliver safe, effective therapeutics, vaccines and diagnostics to patients.
“It’s unfortunate it took a pandemic for this to happen, but it can be a good recipe for the future,” Chad Clark, president of Precision for Medicine, told BioSpace.
Precision for Medicine describes itself as the first biomarker-driven clinical development organization.
Precision for Medicine brings the lessons learned from multiple trials throughout the world to its recently announced collaboration with Budapest-based Karyopharm Therapeutics. Precision for Medicine will manage the first global randomized clinical trial for low dose selinexor (XPOVIO®), an XPO1 inhibitor, in hospitalized patients with severe COVID-19. The 230-patient trial will be conducted in the United Kingdom, Italy, France, Spain, Germany and Austria.
“As companies race to explore new therapeutic solutions to fight COVID-19, clinical trials will be challenged with aggressive timelines, the need to adhere to evolving protocols and guidelines, and the use of advanced technologies for data collection and monitoring,” Katerina Kaleova, M.D., medical director, Precision for Medicine, said in a statement.
Working with Karyopharm to engage and address authorities’ comments during the trial review stage, the companies were able to achieve in just days what normally takes many months for the launch of a global randomized clinical trial.
Even before the COVID-19 pandemic, drug developers were beginning to use digital health technologies to work remotely and to engage patients for trials with low levels of recruitment. The pandemic accelerated those efforts, especially when related to COVID-19.
“COVID-19 studies are starting at an impressive rate,” Clark said. That’s possible because sponsors and CROs are looking more closely at their standard operating procedures. “If a procedure doesn’t improve quality or safety, all you’re doing is increasing paperwork. We don’t have time for that.”
To help its clients’ trials – often in rare diseases – run smoothly, Precision for Medicine uses telehealth, wearables to monitor patients and at-home infusions. It even uses phlebotomists to conduct safety monitoring and check patients’ vital signs. “Necessity is the mother of invention,” he quipped.
Depending on the healthcare system, it’s also able to access some electronic health records (EHRs) directly and ingest that data in real time. “This is highly efficient and eliminates the need for separate data entry,” he said.
A natural language program (NLP) reviews PDF that may be tagged to the EHR, searching for genomic data that can be used for analysis. NLPs have some challenges, Clark admitted, “particularly with unstructured data, but genomic reports can be read extremely accurately.” Even in the EU, where patient privacy laws are quite stringent, monitoring agreements can be forged to allow NLPs to access EHR data.
Regulators are invested in shortening development timelines, too.
“In the U.S., the FDA has its coronavirus treatment acceleration program (CTAP),” Clark said. “I’m impressed with how little information you need (compared to a traditional (investigational new drug – IND – meeting) in order to receive a substantive response. It’s discussing programs at a higher level than it has historically.
“The FDA is motivated to ensure patient safety and to work with companies to get programs into trials as quickly as possible,” Clark said. “CTAP, for instance, fielded approximately 1,000 questions from developers last week and the FDA responded (to most, if not all) within 24 hours. Instead of scheduling pre-IND meetings, FDA personnel are engaging in real time. We had a client get FDA feedback in one hour. We received feedback on a diagnostic question for another program just after midnight. They’re working around the clock.”
“In Europe, investigators are submitting dossiers to the EMA in pieces, as information becomes available. It’s offering verbal consent,” Clark said.
In the UK, the National Health Service established a patient hotline directing them to specific hospitals, based upon a survey of their condition. Drug developers can use that to determine the best sites to host particular studies.
After speeding up for COVID-19, Clark doubts the regulatory and drug development system will ever return to its slower ways.
Parallel workflows are one example. Some companies (with funding from the Bill & Melinda Gates Foundation) are developing manufacturing facilities while the therapies or vaccines to be manufactured there are still being developed.
“To some degree, we’re seeing variations of that in cell and gene therapy markets now,” Clark added. “They’re in early trials, but they essentially have built their manufacturing capacity through the first few years. Once companies have enough data to proceed, they are going all in. Vaccine development for COVID-19 is a reflection of that.”
Precision for Medicine’s marriage of it clinical trial operations and advanced analytics teams are another example of streamlined efficiency that other programs can adopt. With this approach, Clark said, “You have a biologically informed decision making that may include diagnostics” to supports patient stratification. That may result in a companion diagnostic – another revenue stream – for the developer.
Adaptive clinical trials also offer benefits that will carry forward after the pandemic ends. With COVID-19, “Most of the trials we see are single arm studies. They have a lot of flexibility in defining standard of care,” because there is no regulatory-approved therapy. Consequently, “Regulators are allowing modifications to dosing regimen. There’s a lot more interim analysis of efficacy or lack thereof, so trials can terminate quickly.”
Eventually, trials will need to use control groups. Antibody testing, to determine definitively who has or has not had COVID-19 will be the first step in identifying who could be in a control arm, he said.
The COVID-19 pandemic forced a mindset change within the industry, causing developers and regulators alike to examine what they were doing. More efficient processes are resulting that deliver therapeutics, diagnostics and, eventually, vaccines, as soon, and as safe, as possible.
