Game-changing early detection technologies

“Precision” or “personalized” medicine seeks to provide a bespoke therapy for the right patient – with the right treatment at the right time – by adjusting for the nuances within an individual’s genetic profile, health records, and lifestyle. These drugs can produce unprecedented clinical effect with low toxicity compared to other therapies by relying on molecular structures that are not present in all patients. For example, patients may be screened by identification of novel biomarker(s) to guide clinical decisions. The recent clear trend is towards an increase in the number of precision therapeutic products that have received regulatory approval dependent upon the development and validation of a biomarker assay, such as a companion diagnostic (CDx) test, as we have previously discussed here.

In addition, FDA has recently announced a landmark proposed rule, which would make explicit that certain in vitro diagnostic products (IVDs) that are laboratory developed tests (LDTs) are medical devices as defined by the Federal Food, Drug, and Cosmetic Act (FDCA) and will be regulated by the Agency accordingly, including requiring premarket review. Historically, the FDA has not attempted to require compliance for LDTs, with the exception of certain test categories, such as direct-to-consumer tests, some pharmacogenomic (PGx) tests, and tests that respond to public health emergencies. However, given that today’s LDTs often rely on highly specialized components with complex functionalities involving bioinformatics, software development, and underlying specialties such as genetics for next generation sequencing (NGS) test systems, FDA has become increasingly concerned that such tests are being offered without assurance that they work.

FDA has signaled its intention to finalize the proposed LDT rule by April 2024, as we have also discussed here. Although FDA faces numerous hurdles before final implementation, as we have outlined here, the interplay between drug and device approvals is clearly under scrutiny and only becoming more complex. Industry stakeholders must plan accordingly to future-proof their development strategies.

Regulatory development for precision medicines: the road ahead

So, where does this leave management teams with early research programs seeking to develop a cell or gene therapy or other complex therapy that may have profound benefits for the public health yet raises novel issues from a regulatory perspective?

First, think through the proposed timeline for development milestones, market access, and commercialization of your product(s) and associated tool(s) required for approval and administration of the overall therapy. The more novel the accompanying tool(s), the earlier FDA engagement should begin. Early, meaningful engagement with FDA may become crucial when exploring innovative tools with which the Agency may have less experience than industry.

Moreover, if there is any question of whether FDA may view an associated tool as a device, it is best to start this review process sooner than later. Waiting too long, or learning late in the process that a test could require further interactions with FDA and potentially significant further investment and resources, could significantly slow product rollout and increase time to market. Consequences could be especially devastating if the competition is better resourced and/or more sophisticated.

Second, understand and take advantage of available FDA programs and appropriate funding opportunities, especially in the context of the rare diseases for which precision medicines may provide the only possible hope to patients. Within recent years, FDA has introduced a number of pilot programs that sponsors should consider as an opportunity for enhanced engagement.

For example, earlier this year, FDA announced its Support for clinical Trials Advancing Rare disease Therapeutics (START) program, which will offer additional meetings with the Agency to sponsors of novel drugs that aim to treat rare diseases. Eligible drugs include both biological drugs regulated by FDA’s Center for Biologics Evaluation and Research (CBER) that are a gene or cellular therapy intended to address an unmet medical need as a treatment for a rare disease or serious condition, as well as products regulated by FDA’s Center for Drug Evaluation and Research (CDER) that are intended to treat rare neurodegenerative conditions, including those of rare genetic metabolic type. See more details here.

Specifically in the context of IVDs, FDA has also introduced a new pilot program designed to improve transparency for oncology drugs that rely on in vitro diagnostics to identify patients who may benefit from a particular treatment. FDA recognized that while oncology drugs are often approved with an accompany IVD, a sponsor may receive approval of the drug before a corresponding companion diagnostic is authorized, which creates a gap that is often filled by LDTs. We’ve also analyzed these opportunities here. While this pilot was announced prior to the proposed rule on LDTs, it nevertheless highlights that the Agency hopes the new program will help regulators have more confidence in future drug-device oncology combination products.

In addition, FDA recently announced grant opportunities through its Critical Path Initiative to help foster drug product innovation, and has previously identified genetic tests and personalized medicine as exemplary areas of interest for partnerships. Non-dilutive funding opportunities may also be available through government grants, such as from the Advanced Research Projects Agency for Health (ARPA-H) research funding agency. The Novel Innovations for Tissue Regeneration in Osteoarthritis (NITRO) program, for example, supports research in a number of areas including those intended to develop replacement joints from a patient’s own cells. 

Finally, stay engaged. As we have described above, FDA has already introduced a number of key programs to support closer interaction with the Agency to foster an approval ecosystem promoting the development of drugs and biologics that treat rare diseases. We expect the steady pace of industry guidances and new opportunities to continue in 2024 and beyond. Having trusted regulatory advisors who understand the Agency’s priorities and policies can help in managing risk and better prepare to meet your commercial objectives.    

Investments in pharmaceutical development to improve patient health and clinical care remain strategic priorities for life sciences companies, innovative emerging companies, and their investors. According to the Personalized Medicine Coalition’s (PMC) latest research, precision medicines totaled at least 25 percent of new drug approvals by FDA over the last eight years. While FDA engagement is but one of many business decisions required to advance a therapy to market and propel a company towards commercial success, management teams ignore the importance of having an early and clear regulatory approval pathway at their peril.