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Gaining New Indications With Real World Data: The 505(b)(2) Sweet Spot

Gaining approval of new indications for approved or “old” drugs has always been one of the great advantages of the 505(b)(2) regulatory pathway. Couple that with the FDA’s recent enthusiasm for using real world evidence (RWE) to expand a drug’s indications, and you have a strong incentive to get new indications approved particularly, but not just for, oncology drugs.

Premier Consulting has been at the forefront of using RWE to support product approvals. We have applied RWE to submissions for ultra-rare and oncologic diseases. The attendance of one of our Strategic Advisors, Dr. Ruth Stevens, at the recent FDA Public Workshop to discuss the Framework for Regulatory Use of RWE confirmed that our strategies for leveraging RWE in regulatory submissions are cutting edge.

How Do You Get a New Indication Approved?

If done well, getting approval of a new indication for an already approved drug can be simpler than you might think. Depending on the drug and the available information, in some cases no new studies may be required. In other cases, the available information may need to be supplemented with new clinical data. Of course, some Sponsors choose to perform a full clinical program, but for most products this is not necessary.

Of course, it helps to have a thorough knowledge of which data are appropriate and how to get FDA agreement on the use of data to reduce the size and scope of the development program. If that sounds familiar, it is, because this is classic 505(b)(2) development strategy.

The Use of Real World Evidence Gains Momentum

As we previously blogged earlier this year, as part of the 21st Century Cures Act, the FDA was tasked with developing a framework to evaluate how the use of data from sources other than traditional clinical trials may be used to support drug approvals. In that blog, the pros and cons of using RWE were discussed.

The definition of RWE, as provided in a review article by senior members at the FDA, is “information on health care that is derived from multiple sources outside typical clinical research settings, including electronic health records, claims and billing data, product and disease registries, and data gathered through personal devices and health applications.”

We also noted in the blog that use of RWE is already underway for devices, and that the FDA Guidance Use of RWE to Support Regulatory Decision-Making for Medical Devices (draft issued in July 2016, now finalized on 31 August 2017) recognizes the value of using RWE in understanding benefit-risk profiles, supporting an expansion of indication, or a newer version of an approved device, and potentially to aid in regulatory decision-making.

So what is the situation for drugs? In an article published in a Nature review in February of this year, Richard Pazdur, Director of the Office of Hematology and Oncology Products (OHOP) and Acting Director of the Oncology Center of Excellence at the US Food and Drug Administration (FDA) partnered with Associate Director and Acting Deputy Director of OHOP, Gideon Blumenthal, to write that RWE “could be useful for the expansion of labelled indications to patients with rare cancers, potentially enabling a better understanding of patient populations not typically studied in pivotal trials, and of the various dosing and safety issues that arise in clinical practice.”

Enter Commissioner Gottlieb

Using RWE to get new indications approved is a policy advance that is “going viral at FDA,” announced FDA Commissioner Gottlieb in a speech to the 2017 AdvaMed (MedTech) Conference.

Commissioner Gottlieb noted that “some of the most creative, and forward-leaning advances in regulatory policy involve what we’re doing on the device side of FDA’s house”. He stated that in the last 3 years, RWE has been used in the approval of more than 8 new medical devices and in the expansion of use of 6 technologies, and that “increasingly, medical device makers are also meeting their post-market study requirements by leveraging real world data sources.”

Further, Commissioner Gottlieb indicated that the standards in the device guidance are being incorporated into policy for all medical products. The modern regulatory concepts implemented for devices include the focus on a benefit-risk framework that looks across the life cycle of a product, the use of patient preference information to support regulatory approval, and the shift of pre-market data collection to the post-market setting.

Using Real World Evidence to Expand Your Indication

While the FDA cautiously points out the limitations of RWE and the need to improve the collection, and therefore quality, of real world data, its acceptance is clearly gaining traction at the FDA.

At Premier Consulting, we have been successfully leveraging RWE in development programs for products intended to treat ‘ultra-rare’ diseases. For these extremely rare diseases, it can be logistically impossible to conduct traditional studies in so few patients.

To use RWE for an ultra-rare indication, it is essential to gain a thorough understanding of the natural history of the disease and the expected benefits of treatment. The natural history elements include:

  • the pathophysiology of the disease, e.g. are there different phenotypic presentations and what is the extent of heterogeneity among patients?
  • the time course of clinical changes (including biomarkers) on the progression of disease
  • the mechanism of action of the proposed product.

What Types of Data Can Be Used?

Generally speaking, any data that supports the safety or efficacy of the proposed product can be useful. Keep in mind that the way the data was collected will influence its utility.

Data may come from physician records, electronic medical records, clinical research, claims data, prospective observation data, surveillance, mortality databases, published literature, Database of Abstracts of Reviews of Effects (DARE), administrative data, disease or device registries, pharmacy data, mobile devices, consumer data, even social media sources.

From these sources data, on the patient population, dose, treatment, outcome, adverse events, etc., can be used to prepare patient narratives in the marketing application.

Real World Evidence and the 505(b)(2) Pathway

The use of RWE in product approvals is closely intertwined with the 505(b)(2) pathway. Expansion of an indication via data collected outside of the Sponsor’s own development program allows you to utilize the 505(b)(2) pathway. And leveraging available information to avoid unnecessary studies is what we do.

In these times of policy change at the FDA, it makes sense to talk to Premier Consulting’s experts who have already been leveraging RWE to support product approvals. A knowledge of which data are useful, how and when to discuss the data with the FDA, and how to leverage the data in an FDA submission will save your development program valuable time and money.

Contact us to discuss your development program.


Angela Drew, PhD
Product Ideation Consultant

Ruth E. Stevens, PhD, MBA
Strategic Advisor