FDA Guidance: Doors Open

Clipart Illustration of an Open Office Door With An Open Sign HaOn Wednesday, April 23rd, the FDA hosted a webinar to explain the Draft Guidance for Industry Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Development Drug Products for Treatment. FDA briefly reviewed the document and took questions in real time. See my original review of the Guidance document for more details on the various elements of the Guidance. This post focuses on what we learned in the webinar.

Dr. Janet Maynard began by explaining that a Guidance summarizes FDA’s current thinking on a topic, and it is intended to assist pharma in developing drugs by establishing expectations for the approval process. She said it is not a “roadmap” as every drug is different. However, Dr. Maynard said a Guidance can catalyze drug development, and that is what FDA is hoping for here. Even though it is in draft form, this Guidance is in effect now and sponsors can rely upon it in discussing clinical trials with FDA.

As I’ve noted previously, FDA does not have a preference for one ME/CFS case definition over another. Drug sponsors can select among the ME/CFS case definitions, and they must provide FDA with justification for that choice. The goal is a well defined patient population, and FDA believes that is achievable here as long as the sponsor is very clear about the criteria.

The Guidance states that clinical trial endpoints (drug effects) should be measured with Patient Reported Outcomes or PROs. Dr. Badrul Chowdhury from FDA stated that PROs are preferred because this disease is currently based on patient reported symptoms. Objective measures could also be used if they are meaningful, but there are not accepted objective measures at this time.

My understanding is that a drug that changes NK cell test results will not be seen as “effective” without a PRO that indicates the patient feels better. The same is true for exercise testing. A drug that improved anaerobic threshold measures would still need to improve how the patient feels or functions. However, FDA was clear that they are open to using PRO instruments developed for other conditions (which is good because they could be used now) or working with sponsors in developing new PROs, such as one specifically designed to measure an improvement in post-exertional malaise.

Drug safety is always a concern, especially in ME/CFS where drugs are likely to be used for a long time. One question asked about safety data required in drug repurposing trials, and FDA said that they would consider safety data from other studies but there would still need to be a trial in an ME/CFS population. Dr. Maynard said, however, that in balancing safety with long term risks of the disease, FDA is very focused on evidence of efficacy because treatments are needed.

A number of questions focused on issues related to combination drugs. This is not surprising, given that one clinical trial of a combo treatment is currently enrolling. There are rumors of one or two other possible combination treatments in the works, too. FDA pointed out that clinical trial design of combination treatments is challenging, and they encouraged possible sponsors to request meetings with the review division to discuss as early as possible.

In response to a question about natural history, FDA said that sponsors will not be required to show data on the natural history of ME/CFS. Data from the placebo arm of the trial can be sufficient. Another question focused on the inclusion of homebound patients in clinical trials. FDA said they encourage including such patients, and noted that endpoints should be tailored to that specific population. A panelist also noted that a severely impaired population might show a better efficacy of a treatment and that would be an advantage to such a trial.

When asked if FDA understood the desperation of ME/CFS patients and the dire need for treatment, FDA replied that this is precisely why they prepared this Guidance. Dr. Chowdhury said that guidance documents are not common in conditions that do not already have drugs moving through the pipeline. FDA hopes this Guidance will encourage drug development, but the only outreach to drug developers is through the Federal Register. While that is disappointing, Dr. Maynard and the other panelists repeatedly said that they are ready to work with sponsors. They encouraged early meeting requests so that clinical trial design could be discussed. They are willing to be flexible on endpoint measures. In essence, the doors are open.

What happens next? The public is strongly encouraged to submit comments on the Guidance (instructions below). If you think FDA has gotten anything wrong, then please submit a comment. I’ll share my own public comment with you next week.

  • To submit an electronic comment, go to http://www.regulations.gov and use the docket number FDA–2014–D–0264, or try this direct link. Use the “Comment Now” button to open up a screen to enter your comments.
  • To submit a written comment, be sure to list the docket number FDA–2014–D–0264 on your letter and send it to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852


Disclaimer: I am a member of the FDA’s Patient Representative Program. However, this post represents my personal opinions and are not comments made in any official or formal capacity.


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3 Responses to FDA Guidance: Doors Open

  1. kathy d. says:

    Thank you for posting this and the information you’re included. I’m not sure what I think about this.
    How can the FDA allow development of drugs for ME/CFS when HHS doesn’t promote the fact that it’s a physically based illness? Also, that drug companies as well as the government scientists don’t really know how this disease works nor do they agree on what the disease is.

    I wonder if they’ll look at the Rituxamab studies in Norway for clues as to what to aim at, i.e., B cells or what these companies will strive to do, to focus on, etc. This is fascinating in a way. Are they aiming at the immune system? At alleviating muscle pain? Exhaustion?

    Anyway, look forward to reading more about this while I ponder this topic.

    • Jennie Spotila says:

      A lot of what FDA can do is limited by the drug companies that want to develop drugs. If a company wants to test Rituximab then that will determined trial design, etc. If someone wants to focus on muscle pain, same thing. FDA does not make those decisions. Drug companies decide what they want to work on, and FDA gives guidance on how to do it.

  2. David Egan says:

    Letter to FDA

    Reference: Draft Guidance for Industry Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Development Drug Products for Treatment

    Dear Mrs. Janet Maynard,

    I would like to make a submission to the FDA in relation to it’s Guidance for Industry Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Development Drug Products for Treatment.

    The most accurate and reliable diagnostic criteria are listed here at http://www.me-ireland.com These criteria enable the identification of genuine patients and the identification of subgroups.

    The most accurate biomarkers for the illness and it’s subgroups, identified and verified by scientific research, are listed here at http://www.me-ireland.com/structure.htm#8 . These biomarkers provide a means to identify subgroups and then measure and assess the efficacy of drugs for these subgroups. Biomarkers can be measured at the beginning, the mid point and at the end of scientific trials of drugs to measure efficacy. This focus on subgroups and known biomarkers would enable researchers to overcome the difficulties / obstacles posed by this complex, multi-faceted heterogeneous illness. End point assessments could include changes in biomarkers and correlations of this with improvements in DSQ for Fatigue scale and SF-36 scale and in Health Related Quality of Life measures.

    Health Related Quality of Life could include factors such as resuming full time work or full time education in school / college or no longer using a wheelchair or no longer have to stay in bed most of the day or no longer house bound.

    Safety considerations must also factor in the effects of the illness itself including increased risk of heart attack and certain Cancers and complications of Brain inflammation and damage. Many patients have suffered years of neglect by the medical authorities and their health and condition has deteriorated over time. These risks are mentioned in the research listing section http://www.me-ireland.com/right.htm#l

    I hope this can be integrated into FDA policy regarding assessment of all drugs for treatment of the illness.

    Best Regards
    David Egan.

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