Many thanks to ME/CFS science news analyst Cort Johnson for sharing this perspective on an undertaking so vital to the patient community.
We're not used to federal agencies moving forward with alacrity on ME/CFS issues, but last month’s 90-minute FDA teleconference with chronic fatigue syndrome stakeholders indicated the FDA is doing just that.
(When “Occupy CFS” blogger Jennie Spotila is happy, somebody is making progress; check out her blog here.)
Articulate, and obviously sharp as a tack, Sandra Kweder, MD, deputy director of FDA’s Office of New Drugs, led the telephone conference call.
She quickly demolished any concerns about whether the FDA believes chronic fatigue syndrome is a ‘serious and life-threatening disorder’ - stating that the agency considers ME/CFS on a par with cancer, diabetes, epilepsy, heart failure and other serious diseases.
This was an important statement, given that ‘serious and life-threatening’ is a key criterion in the FDA’s decisions on drugs selected for expedited review.
Let’s take a brief look at the options this designation may open up in future consideration of drugs for chronic fatigue syndrome:
Fast track – Drugs on Fast track status are accorded more frequent meetings with the FDA and are eligible for 'accelerated approval'; and the application can be submitted in pieces rather than all at once.
Accelerated Approval - The FDA can conditionally approve a drug before it has final confirmation of its effectiveness, thereby allowing the drug company to get the drug out to the patients more quickly and giving it the opportunity to raise funds for the final studies. This is particularly important for small drug companies with limited financial resources, such as Ampligen maker Hemispherx.
Priority Review - The FDA will aim to review the drug in six months instead of 10 months.
The FDA's designation of ME/CFS as a ‘serious and life-threatening disorder’ should make it more difficult for the NIH and CDC to justify spending such small sums on ME/CFS, and it gives ME/CFS advocates another plank they can use to promote their cause in the federal arena.
Most of the 90-minute stakeholder teleconference was spent responding to patient questions or statements. During that period we learned that: The FDA has eight ME/CFS 'drug' applications, but...disappointingly (if not surprisingly) most of these concern nutritional supplements and involve small numbers of patients.
Biomarkers, Endpoints - Measures of Success
A major, major question will involve how the FDA should determine whether a drug is effective in ME/CFS. The 'endpoints' measured - the clinical measures that indicate whether a drug works or not - are vital.
I remember one researcher stating that she felt they missed an endpoint in the Fludrocortizone (Florinef) trial (i.e., they didn't include one test); and that if they had included it, the trial might have been a success. Instead, despite Florinef's obvious efficacy for some patients who experience reduced blood pressure when standing, it was deemed not effective at treating ME/CFS, and most doctors will not consider it for ME/CFS patients.
My worry was that if the FDA only took into account published studies it would concentrate on more well-studied but less rigorous qualitative measures such as fatigue and depression questionnaires and ignore less-studied but more rigorous tests that get closer to the biology of ME/CFS, such as VO2 max testing, NK cell cytotoxticity, blood volume, cytokines, etc. We know, for instance, that many doctors including Drs. Peterson, Klimas and Kogelnik routinely use VO2 max tests to assess how effective their treatments are; but the mass of studies the FDA might want to see on those subjects might be missing.
Dr. Kweder, however, stated that the FDA has approved drugs for conditions that affect as few as 300 people, and they are comfortable in using anecdotal data such as doctors’ reports to determine what to look for.
Essentially they will convene the stakeholders - get the experts together in a 'scientific workshop' to be held next spring - and hammer out which biomarkers or endpoints to look for.
This is very good news for ME/CFS patients, and we should look forward to Drs. Peterson, Klimas, Lapp, Bateman, Pocinki, Enlander, etc., providing input on what works in ME/CFS and pushing hard for the inclusion of NK cell functioning, V02 max and other tests at the meeting.
Achhh - the Subsets!
But what about those darned subsets? Say we have a drug that helps 20% to 30% of the patients. That might not be enough for statistical significance in a standard clinical trial. What to do then?
Given the heterogeneity present in ME/CFS it’s clear this issue is going to come up. It wasn't clear what the FDA will do when that happens, but it was clear that they recognize this problem is present, not just in ME/CFS but in many other diseases, and have procedures to deal with it.
Orphaned and Loving It
Kim McCleary of the CFIDS Association (CAA) came up with one of her intriguing ideas, and asked whether a small subset of responders could allow the drug to be put into the Orphan Drug Category.
The FDA Office of Orphan Products division is dedicated to advancing the 'development and evaluation' of drugs for conditions that affect less than 200,000 people in the US. They will even at times actually provide funding for drug development and testing. The Office of Orphan Products played a key role, for instance, in assisting Xyrem (sodium oxybate) to become an FDA approved drug.
With ME/CFS prevalence hovering somewhere around 1,000,000 people in the US, a drug found to assist 20% of these patients could conceivably fit the Orphan Drug status for a 'condition'. My guess is that we would expect several drugs to fit this category over time.
Dr. Kweder thought this was an intriguing idea, and acknowledged the possibility was there.
On the Calendar
The FDA put several dates on the calendar...
CFSAC Meeting - With only one drug under review it's not surprising that the FDA ex-officio member has been notably silent at CFSAC meetings (except for some snores at one meeting (:)) but with the Stakeholder Meeting on track that will change, and the officer will give a presentation at the next meeting to describe the drug review process in detail and bring everyone up to date
Advocacy Webinar - In mid-November the FDA will hold an “Excellence in Advocacy Webinar” designed to help advocacy groups mount effective campaigns for accelerating ME/CFS drug approval.
Ampligen on the Mat - On Dec. 20, 2012, an FDA advisory committee will hold an open meeting to discuss Ampligen's fate - which will be decided, at the very latest, by Feb. 2, 2013.
Spring 2013 - The Big Stakeholder Meeting (Scientific Workshop)
This opportunity for ME/CFS clinicians, researchers, patients and advocates to explore the scientific issues has been pushed back to spring, but that's all right - better later than earlier given what's at stake.
This meeting, which will be open to the public, will identify how the FDA will determine if a drug is effective in ME/CFS, and will set the stage for all future drug applications.
It's also very good timing in one way... By then, the CAA's Biovista study (scouring the FDA drug database for new drug options) should be completed, and could bring more drug manufacturers to the table.
By the way, did you know that the last FDA Stakeholder Meeting held for a disease occurred about 20 years ago with HIV/AIDS?
The FDA organizes meetings involving pharmaceutical companies frequently, but meetings on a specific disorder…those are once every other decade-type meetings. So give your FDA advocates - in particular Bob Miller, Mary Dimmock and Nancy McGrory - big kudos for being bold, innovative AND successful. What a nice combination that is.
Driven entirely by advocates and small grass-roots organizations, the FDA Stakeholder Meeting initiative, thus far, has to count as one of most successful advocacy efforts ever.