Precision medicine development is on the rise. These drugs, which target specific genetic, molecular and cellular markers and provide patients with personalized and targeted treatments, are highly attractive targets for drug developers. They offer great promise for good patient outcomes, particularly in oncology.
But precision medicine development can pose significant challenges as well: getting to a successful regulatory approval requires sponsor companies to embrace many new technologies and systems during the development process. Is your company ready to compete on this new playing field?
Manufacturers are beginning to realize the promise of precision medicines, translating to direct benefit to patients.
“In the past five years, we’ve seen a sharp increase in the number of trials designed with a precision medicine approach,” says Anita Nelsen, vice president, Translational Medicine at Parexel. In 2018, she notes, about one of every four drugs approved by the FDA was a precision medicine therapy, a record high number. “That is the most approvals to date, and we expect it will continue to increase.”
Moreover, she says, precision medicines are 10 percent more likely than others to be successfully launched and added to payer formularies, according to The Innovation Imperative: The Future of Drug Development, a recent study by the Economist Intelligence Unit, commissioned by Parexel. In the oncology arena the study found they performed even better: precision medicines were 26 percent more likely to successfully launch. (Parts one and two of this article series looked at the success rates of adaptive trials and real-world data studies.)
Companies that want to reap those kinds of results and ensure a smooth regulatory approval for their new precision medicines should take a hard look at their current capabilities, advises Nelsen.
“Developing these medicines requires changes to traditional clinical trial designs, as well as the use of innovative testing procedures that result in new types of data,” she says. Making the best use of these innovations and being ready to demonstrate results for regulatory bodies requires specialized knowledge that many clinical development teams don’t have.
The areas where companies are most likely to encounter challenges, she says, are data analysis and workforce expertise, biomarker and diagnostic test development, and cultural awareness.
New regulatory frameworks for precision medicine
Given the scope and potential of precision medicine, the FDA has taken proactive steps to modernize the governing regulatory framework. “Precision guided medications are often able to show strong evidence of efficacy in early stage trials, where patients are selected based on discrete biomarkers and other identifying criteria” says Sugato De, vice president, Regulatory and Access at Parexel. “Early-stage trials that enable a robust regulatory assessment of benefit and risk are accelerating drug approval decisions, allowing patients to gain faster access to innovative therapeutic options” he says.
“Modernizing clinical trials to support patient access to potentially groundbreaking treatments is of paramount importance to FDA, and the agency is working with professional societies, industry groups, and the medical research community to discuss efficient approaches to developing and validating new diagnostics and therapeutics” says De. “The agency is committed to pursuing a regulatory framework that prioritizes novel clinical trials and real-world data solutions to provide robust evidence of safety and efficacy at early stages. In the future, larger studies for certain products with early evidence of safety and efficacy may be transitioned to a post-market setting.”
The promise of novel trial designs may often be delayed by a clinical research ecosystem that has a legacy of executing trials in the traditional Phase I, II and III constructs. “Streamlining product development will require more agile approaches that leverage real-world data, data sharing, and the adoption of trial designs that emphasize demonstrating effectiveness at early stages” says De.
The agency is undertaking several initiatives to incentivize innovative trial designs and evaluate the potential role for decentralized clinical trials. For example, FDA has pioneered the concept of “master protocol trial designs” that can assess, in parallel, multiple drugs compared to respective controls or to a single common control. This infrastructure can be used to adapt trials to incorporate new scientific information (e.g, novel biomarkers) to ensure that trials are efficiently being conducted to target patients with the greatest likelihood of benefit. To this end, FDA has released new guidance for industry on strategies that can potentially accelerate precision medicine development and also guidance on novel risk-based monitoring solutions. These guidance’s, Enrichment Strategies for Clinical Trials to Support Determinations of Effectiveness of Human Drugs and Biological Products, and A Risk Based Approach to Monitoring of Clinical Investigations: Questions and Answers Guidance for Industry, provided concrete recommendations that are intended to reduce regulatory uncertainty.
“In order to fully realize the promise of precision medicine” says De, “the clinical research ecosystem must transform to eliminate barriers between real-world data and traditional clinical trials, so that evidence can be shared efficiently to inform a learning construct for regulatory assessments and healthcare decisions.”
Data analysis and workforce expertise
Precision medicine trials often generate new types of data, such as genome sequencing data, that doesn’t fit neatly into traditional clinical trial structures. Plus, rapid advances in technology have made it possible to generate and analyze huge amounts of data in near real-time, says Nelsen.
Pharma staff need specialized knowledge to manage and analyze this influx of new and vast amounts of data. Not every company has the ability to do such heavy analysis within the context of a clinical development program.
In addition, there are currently no data standards for many biomarker and genomic tests, and that can make it hard to assess the quality of your results and what it means for your study.
“Data accessibility and sharing is also a challenge,” says Nelsen. Precision medicine development may use data from a wide variety of sources, such as wearables, electronic health records, patient-reported outcomes, and complex genomic and biomarker results. Integrating and interpreting this data requires staff who possess up-to-date skills as well as knowledge of regulations and practices that are rapidly evolving.
Precision medicine development often requires deep genomic expertise. Sponsors need to be able to design clinical trials that incorporate genomic information, such as what genetic variants are important for selecting patients, and what is the impact of this variation on study feasibility and patient recruitment. Sponsors may also need to consider available tests are fit-for-purpose for their intended use in a trial or if a new test will need to be developed and if so, what technology is best to generate genetic results. High-level genomics expertise, incorporated early in the development of a new therapy, can increase the likelihood of a successful development process.
Biomarker strategy and diagnostic test development
Another important consideration in securing regulatory success is the early development of a strong biomarker strategy.
Biomarkers are a critical component of precision medicine development and, when used for patient selection in clinical development, are associated with 2-3 fold increase in gaining regulatory approval and often through accelerated pathways. This means they help speed the process in getting new medicines to the patients who need them,” says Nelsen. “Ideally, a biomarker strategy should be adopted early in drug development and evolve with the drug development program as it transitions from pre-clinical to early- and late-phase development.”
Some companies will put off developing a biomarker strategy when they are in the early stages of development. But at a minimum, says Nelsen, their strategy should include collecting and banking samples from clinical trial participants. These samples are a valuable tool for later biomarker discovery and development. Retrospective collection of samples to support biomarker development is very costly and difficult.
In addition, regulators have established pathways for biomarker development, and typically encourage developers to communicate with them early on, to ensure that a biomarker’s development meets expectations for scientific validation. Sponsors also want to ensure that clinical trials are designed to demonstrate the appropriate level of evidence supporting the intended use of the biomarker. This early engagement and planning is critical; it will help ensure that a development program for a precision medicine includes a well-defined regulatory path, including what to file, when to file and what data are needed for the filing.
In some cases, a new precision medicine requires the development of a companion diagnostic test based on a biomarker. This step is often done in partnership with another company, which means tight coordination of clinical trial design, sharing samples and data, and other joint efforts. Ultimately, it will also mean working closely together to pass through regulatory steps, which can be difficult to coordinate.
Another hurdle that is often overlooked until a company is far along in developing a precision medicine: cultural barriers. In some countries, it is very difficult to collect samples for genetic and biomarker research, and without a sufficient number of samples that represent the clinical trial population, it will be hard to demonstrate the safety and efficacy of a new therapy. In addition, adherence to traditional clinical trial designs and resistance to leveraging real-world evidence and data sharing mechanisms may delay drug development.
Navigating these complexities and ever-evolving technologies, while trying to ensure that every step along the way will pass regulatory muster and provide sufficient data for a successful launch of your new precision medicine, is a huge task. And it’s likely to get even more complex in the future, says Nelsen. Parexel’s subject matter experts have direct knowledge of the development and implementation of FDA’s policies with respect to precision medicines, and has successfully supported 14 precision medicine and companion diagnostic programs in the last two years alone. “Partnering with a company like Parexel, which has industry-leading expertise in clinical, regulatory and market access solutions can help ensure an optimal development program that leverages our industry experience and FDA’s new and evolving toolkit to speed your way to regulatory approval,” says De.
Ready to explore innovative clinical trial designs that can boost the success of your products? Parexel’s experts can help your company to develop truly innovative clinical studies and regulatory strategies that result in impactful drug development.