Dec 20th: High Noon for Ampligen and Chronic Fatigue Syndrome

by Cort JohnsonAmpligen’s time is finally here.  Twenty years of effort and hope  will culminate on the early evening of Dec 20th, when, following an  all-day hearing,  an FDA Advisory committee  will determine  Ampligen’s fate. Palms will be sweating and hearts will be pounding that evening as patients, physicians and their supporters and researchers with decades of work on the line  await what will be a momentous  decision.Produced by Hemispherx Biopharma, Ampligen is and has been the only drug under development for chronic fatigue syndrome for over twenty years.  No other drugs are waiting in the wings and no other companies appear interested in  putting  years of effort  and millions of dollars into producing or even testing a  drug for this disorder.It’ll all come down to 6-10 or so independent ‘experts’ opinions on whether this drug is safe, effective and worth putting on the market.Prior to  the big decision we’ll see presentations from Hemispherx, the FDA and ME/CFS patients.   Dr. Bateman, Dr. Snell and Hemipherx representatives will present for Ampligen.LOCATION: Open to the PublicAnybody can come and we hope as many people as possible  come and if they wish, give testimony.  Patient Testimony will be given in 3-minute slots  from approximate 1pm to 2:30December 20, 2012: Arthritis Advisory Committee Meeting Announcement

Center	Date	Time	Location
CDER	December 20, 2012	8:00 a.m. to 5:00 p.m.	FDA White Oak CampusBuilding 31Great Room (Rm. 1503)White Oak Conference Center10903 New Hampshire Avenue Silver Spring, Maryland

 For Directions and other InfoHemispherx is likely to face tough questioning at the FDA Advisory Committee meeting for AmpligenTOUGH ENVIRONMENTAccording to someone who’s been there, FDA Advisory Hearings  tend to be in-your-face type affairs in which tough questions  and a critical attitude are the norm. If Hemispherx  is getting whacked around at the hearing don’t attach too much significance to it;  every pharmaceutical company gets hammered at these hearings – even those that get their drugs approved.My understanding is that there will be two presentations; the FDA will present its interpretation of the data and Hermispherx  with Dr. Bateman, Dr. Snell and its own raft of professionals will present its case. The FDA Advisory Board, made up mostly of rheumatologists  will pepper each group with questions and come to a decision on three questions.

• Does  Ampligen work ( efficacy)?
• Is Ampligen safe?
• Do Ampligen’s benefits outweigh its risks?

Each member will answer each of these questions live and we’ll get  their decision in public  that day. From there the FDA will take their reports into account and submit their final ruling on Feb 3rd, 2013. They almost always follow the decisions of the Advisory Board.Still Some UnknownsThere’s still quite a bit about this meeting that we don’t know and that the FDA probably won’t share until 2 days before the meeting. Take no offense at this – this, for some reason,  is standard FDA procedure. (The FDA states they will provide the information at least two day before the meeting, which everybody is taking to mean it will happen two days prior. )At Least Two Days Before the Meeting..We Will Know

• Panel Makeup – The final makeup of the panel.  We do  know that the panel will be made up of persons from the Arthritis Advisory Committee and perhaps others but we’re not sure who.  The FDA website states the  committee is made up of 12 slots, six of which are vacant (including the Chair  ). Of the six persons  listed on the website one of them, Dr. Irwin Russell, is director of the Fibromyalgia Research and Consulting Clinical Research Section of South Texas. Another is an immunologist; none of the others, at first glance, have any indirect connections with CFS or FM.

• Patient Advocate – the identity of the ‘Patient Advocate’, who presents the needs of the patient community to the panel will be listed.

• Discussion Points/Questions – Hemispherx will want to rest up beforehand because the FDA may list a series of questions  they want information on just  two days before the epochal hearing takes place. Hemispherx may  be cramming all the way up to the hearing..

• Webcast Link – We’ll  get the link for the webcast.

The information will be available here or maybe here; it’s not entirely clear from the notice..STAR ALIGNING? Ampligen has been under review of one sort or the other since the nineties, but after  a surprisingly good year for Ampligen there is  good  reason to hope for a successful outcome.   In July the FDA reversed a devastating 2009 decision requiring Hemispherx to produce new  expensive studies which  appeared to  put Ampligen out of reach for good.  With chronic fatigue syndrome gaining more prominence, though, and with  the FDA being given a  new mandate to give  serious, underserved  illnesses a foot up,  Ampligen was  back in the mix in 2012.Key Legislation Provides An OpeningThe 2012 FDA Safety and Innovation Act (FDASIA) passed in July appears to  have played a key role in reversing Ampligen’s fate. The FDASIA encouraged the FDA to use a process called ‘accelerated approval’ which allows the Agency to conditionally approve drugs  for ‘serious and life-threatening illnesses’ while  drug companies worked on proving efficacy. This is a perfect mechanism for small drug companies like Hemispherx which would be allowed to market the drug and use the profits to fund further studies it couldn’t otherwise undertake.Have the pieces come together for Ampligen and Hemispherx?Coming just two days after the passage of FDASIA, the FDA turnaround  on Ampligen might indicate the FDA  is using the drug to make a statement regarding its willingness to follow FDASIA guidelines.  Indeed, Sue Sutter, a noted business/pharmaceutical journalist suggested  the FDA’s change of direction on Ampligen may have been directly  influenced by the  FDASIA.More groundwork was laid on Sept 13th when FDA Deputy Director, Sandra Kweder, M.D. publicly stated on an ME/CFS Teleconference that the  FDA considers ME/CFS to be a “serious and life threatening disorder”.  An FDA notice for the meeting  that specifically mentioned ‘accelerated approval’ and ‘unmet medical needs’ with regard to drugs for ME/CFS indicated that the FDA, again, was specifically drawing attention to FDASIA guidelines.The FDA’s decision to hold an  ME/CFS  advocacy teleconference and use ME/CFS  to produce it’s first Stakeholders Meeting for  a disorder in decades next year  also suggests a positive stance by the FDA.  (One FDASIA provision calls for more patient involvement.)  Sue Sutter  called these efforts “a major step in the FDA’s efforts to raise the profile of CFS as a drug development target”.Finally a Jan 2011 decision to consolidate, after being bumped around to six divisions,  oversight of CFS treatments in the Division of Pulmonary, Allergy and Rheumatology Products, suggested the Agency was trying, finally, to get its arms around this disease and its challenges.THE PLUS’SThe Drug

• Ampligen out-performed a placebo in exercise trials
• Patients on the drug were able to reduce their use of other medications, some of which can  be harmful
• Over 1,000 patients have been administered over 90,000 doses of the drug safely
• Even long term use of Ampligen appears to be safe (ie does not cause disease)
• Significant buy-in from physicians who have administered the drug and patients who have taken it.  (See Dr. Peterson talking about Ampligen in the past   Read Kelvin Lords experiences on Ampligen here).

The Disorder

• Chronic fatigue syndrome is a relatively common disorder with no FDA approved drugs (and no other drugs in sight) which presents high economic costs to people who have it and to the  nation as a whole
• CDC figures suggest that chronic fatigue syndrome is functionally as disabling as multiple sclerosis and 10 times as common
• Other disorders with few FDA approved drugs have been given more latitude with regard to drug efficacy at the FDA; ie if no other treatments are available the FDA is willing to relax its efficacy requirements.
• FDASIA passage supports accelerated approval in cases where serious unmet needs are present and the drug is safe.

The MINUSES

•  The biggest hurdle Hemispherx has to deal with is the age and number  of its studies.  In 2009 the FDA wanted a brand spanking new study with lots of bells and whistles.  The FDA relinquished that stance earlier this year but Hemispherx could be penalized for not being a billion dollar pharmaceutical company with resources to burn. Hemispherx’s re-analysis of its original data had Ampligen performing better. Will that be good enough?

• Controversial Disease – with a poor definition. Will the disorders negatives trump its positives and the community’s needs? No federal agency has ever made the CFS communities needs a priority. Will the FDA be the first?

DECISION TIMETaking Responsibility - The FDA rarely does not follow the decisions of its independent reviewers but the responsibility for the final decision is theirs.  They, of course, contributed to Hemispherx’s dilemma by moving the drug around to six regulatory teams.  Frustrated with these kind of bureaucratic bottlenecks and the slow pace of drug approvals, Congress acted in 2012 to make the FDA work more effectively for chronically ill people in the U.S.It’s hard to see what the FDA has to lose by giving Ampligen Accelerated Approval status. They know the disorder is serious, they realize the community has huge unmet needs, they have proof of efficacy and most of all, they know the drug is safe.POTENTIAL GAME CHANGERAmpligen approval would change how ME/CFS is viewed leading to more respect and more fundingIf approval occurs patients will get access to a drug that’s worked well for many, doctors will view ME/CFS as more of a treatable disorder and immune research will heat up.  Future studies examining Ampligen’s effects could very well pave the way for a biomarker and uncover subsets.FDA approval would also give pharmaceutical companies the message the FDA is serious about finding ways to get drugs to this community and that it will work with them where it can to do. A thumbs down could suggest the opposite.Maybe the biggest change, though, would be a change in context for ME’/CFS.  If you can change the context in which a thing occurs opportunities that were denied to it come naturally. An FDA approval would make this disorder more real as a disorder thus giving it more access to the opportunities other ‘real’ disorders have. The FDA does not approve drugs for figments of the imagination; it approves drugs for HIV, pneumonia and cancer.  Ampligen approval would begin to thrust chronic fatigue syndrome into that realm and  disorders like that  get respect, they get interest and they get funding.The final decision for Ampligen will come on Feb 2nd.