Note: You can read the FDA Guidance HERE.
RAPS Regulatory Focus Today
Posted: 10 March 2014
By Alexander Gaffney, RAC
The US Food and Drug Administration (FDA) has released a new draft guidance document intended to expedite the development of drugs to treat chronic fatigue syndrome (also known as myalgic encephalomyelitis)—a poorly understood condition that has recently been subject to significant interest by FDA regulators.
Chronic fatigue syndrome (CFS) affects patients by causing severe, persistent and often debilitating fatigue. Little is known about the underlying causes of the condition, or even if it is a single condition or a group of related conditions. Despite numerous theories—including some that have since been discredited—there are no tests to determine its cause.
That leaves patients in something of a bind: The effects of CFS are real, but without an understanding of its underlying causes, researchers and manufacturers are unable to target potential or existing therapies to treat it.
That bind was put on display and amplified in February 2013, when FDA—following the advice of one of its advisory committee panels—did not recommend Hemispherx's Ampligen (rintalolimod), saying it needed additional clinical evidence and data before it could consider approving the drug.
But CFS patients are also the first to benefit from a special provision of the Food and Drug Administration Safety and Innovation Act (FDASIA), which calls for FDA to set up a "Patient-Focused Drug Development Initiative" to better take into account the views of patients during the regulatory review process.
"The human drug and biologic review process could benefit from a more systematic and expansive approach to obtaining input from patients who experience a particular disease or condition," FDA explained in a Federal Register posting announcing the program in September 2012.
In October 2012, FDA sat down with CFS patients in order to hear their views on the regulatory process, most notably including their tolerance for risk.
Now FDA is out with a new draft guidance document on how companies can develop drug products intended to treat CFS—a guidance that appears to take patient preference into account.
The guidance, Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Developing Drug Products for Treatment, makes frequent note of the "unmet medical need" faced by CFS patients. That need means that CFS treatments will be eligible for special FDA regulatory designations, such as fast track designation, breakthrough therapy designation, accelerated approval and priority review status.
But it also addresses several difficult-to-answer questions. For example, how do you run a clinical trial on CFS patients when you have no idea if a person actually has CFS?
FDA's guidance has an answer: It's not entirely sure either.
"At this time, the FDA does not recognize any particular disease definition, nomenclature, or diagnostic criteria for CFS/ME as the most appropriate for use in clinical trials of new drug products," it wrote. However, it says that "any case definition or criteria" can be used by a sponsor to define a patient population. Those criteria or definitions will need to be justified to regulators, it said.
As such, FDA also said it will be recommending some rather unique endpoints for CFS treatments. Efficacy endpoints "should include patient-reported symptoms using well-defined and reliable patient-reported outcome (PRO) instruments," FDA wrote.
"These patient-reported symptoms can include any scientifically supported and logical combination of symptoms that are common in CFS/ME," it added. Objective measures should also be considered, but are not necessarily required.
FDA said that "for most drug products, phase 3 trials that use a single primary efficacy endpoint with supportive secondary efficacy endpoints should be adequate to establish efficacy, provided the efficacy findings are robust and clinically meaningful."
The remainder of the guidance document goes into detail about specific efficacy trial considerations, such as trial design, efficacy endpoints, and trial duration.
FDA also said that in general, it will expect drug applications to be supported by two "definitive"—usually taken to mean Phase III—trials. Long-term safety data should also be collected, FDA wrote.
Comments on the guidance will be accepted by FDA through 10 May 2014.