Remarks by Scott Gottlieb, M.D.
Commissioner of Food and Drugs
FDA Public Workshop on Tissue Agnostic Therapies: Regulatory Considerations for Orphan Drug Designation
White Oak, MD

(Remarks as prepared for delivery)

Thank you for the opportunity to join you today.

We’re seeing tremendous opportunity from our ability to understand, and target, the underlying molecular basis of disease. It’s much less common today, when a new medicine is put into development, where the biological rationale for how it should work isn’t clearly understood at the very outset.

In fact, more and more, if you look at what’s going on in the investment side of the life science sector, having a firm understanding of the mechanism of action is increasingly a pre-requisite to funding a new drug development program.

It’s just a matter of fact, that a new drug is less likely to be developed in the first place, if the biological rationale for a new molecular entity isn’t clearly established at the very beginning.

This wasn’t always the case.

And it wasn’t the case just a short time ago.

A few decades ago drug makers were investing in huge facilities to do high throughput screening as they sifted through random “hits” to find drugs like needles in a haystack.

Now medicines are designed more intelligently, against pre-determined targets, on molecular scaffolds, one atom at a time.

This new opportunity also compels FDA to adapt our policies to accommodate, and leverage, these same scientific advances.

We’re here today to talk about some of these openings.

Being able to confront disease based on how it develops, and not simply on how it appears at the time of diagnosis, is a key evolution in how we approach scientific research and medicine.

And these approaches are not just theoretical, anymore.

FDA is opening the door to these methods; and embracing new regulatory constructs like basket trials and master protocols that make these approaches easier and more efficient.

One opportunity we’re going to discuss today, and which I’m especially focused on, is the prospect for drugs to be designated as orphan drugs based on the molecular subtype of the disease. I want to make sure we’re taking every possible step to advance these opportunities. We want to be proactive. We will lean forward.

We want to make sure we properly align policies and incentives to encourage more intelligent, and effective, drug development. This challenges us to take up some novel policy questions. That’s what we’re here to probe today.

We’re now able to target very rare subtypes of disease with treatments that are tailored in a way that allows them to intervene at the molecular formation for a condition –- and deliver superior results. In this way, we’ll have more opportunity to arrest or even prevent disease altogether – and not just treating symptoms, or managing to slow the progression of a condition, or the rate of decline in function that comes from certain conditions.

This is already happening in multiple clinical settings.

But these approaches are most obvious in cancer.

Historically, FDA has used a histology-based approach for oncology drugs, both in the designation of diseases as orphan conditions and approval of indications for treatment of tumor types where it was based on the anatomic site or histology.

Evolving knowledge of the molecular and genetic basis of cancer has led to refinements of the categorization of malignancies, based on molecular markers. And so the new guidance that we intend to develop on tissue agnostic drug development approaches will speak to these opportunities, and how we intend to consider orphan drug designation requests in these situations.

We’ve already granted three such orphan drug designations – two in cancer, and one for a rare, inherited eye condition call retinal dystrophy. These same approaches and principles may also lead to much more efficient development programs.

In cases where we can generalize a response based on a molecular subtype, successful “basket” trials based on biomarker type will be more efficient, faster and cheaper, allowing patients to access scientific advances sooner.

And so, among the questions we’ll be taking up today are the evidence needed to consider a biomarker as defining a tissue agnostic disease for purposes of orphan drug designation.

We’ll also ask questions about how FDA should approach orphan drug designation requests for a product intended for treatment of a tissue agnostic disease as well as a histology-specific disease.

In very short order, it seems clear that our understanding of diseases is changing from a site and tissue orientation to a molecular basis. This is especially true in oncology.

In this medical paradigm, our approach to medicine will be through more tailored therapies aimed at a molecular target.

Today we’re going to advance the discussion on how we capitalize on these scientific opportunities as a matter of policy, and how FDA adapts its approaches to embrace and foster the development of these new scientific and clinical approaches to make sure we bring these opportunities to patients.