CFS and Ampligen: A Creative Solution from the FDA?

[JohnnyD]

The FDA is going to hold a little webinar on February 4th an 5th. The following was posted to the federal register on 01/15/2013.
Creating an Alternative Approval Pathway for Certain Drugs Intended to Address Unmet Medical Need; Public Hearing

The Food and Drug Administration (FDA) is announcing a public hearing to obtain input on a potential new pathway to expedite the development of drugs, including biological products, for serious or life-threatening conditions that would address an unmet medical need. The drug’s safety and effectiveness would be studied in a smaller subpopulation of patients with more serious manifestations of a condition. Such a pathway could involve smaller and more rapid clinical trials than would occur if the drug were studied in a broader group of patients with a wide range of clinical manifestations. The labeling of drugs approved using this pathway would make clear that the drug is narrowly indicated for use in limited, well-defined subpopulations in which the drug’s benefits have been shown to outweigh its risks. The purpose of the public hearing is to obtain information and comments from the public on the need for and feasibility of this pathway and its potential advantages and disadvantages.

Full posting here:
https://www.federalregister.gov/art...-drugs-intended-to-address-unmet-medical-need

This fits CFS and Ampligen to a "T". We know that members of AdCom were calling for the FDA to get "creative". We know that ampligen did not quite fit the FDASIA requirements (they needed a surrogate endpoint). We know that a large trial would be very difficult, given the nature of the disease, and associated problems.

I think the FDA may get it. This could change everything.

 

[Sasha]

Interesting...

I hope this doesn't mean a delay in conditional approval of Ampligen, though.

 

[JohnnyD]

CENTER FOR DRUG EVALUATION AND RESEARCH (CDER)
FOOD AND DRUG ADMINISTRATION DEPARTMENT OF HEALTH
AND HUMAN SERVICES

Public Hearing: February 4, 2013

Creating an Alternative Approval Pathway for Certain Drugs Intended
to Address Unmet Medical Need; Public Hearing

Panel Members

Presiding Officer: Rachel E. Sherman, M.D., M.P.H.
Associate Director for Medical Policy, Director, Office of Medical Policy
Center for Drug Evaluation and Research

Edward Cox, M.D., M.P.H.
Director, Office of Antimicrobial Products, Office of New Drugs
Center for Drug Evaluation and Research
Issam Zineh, Pharm.D., M.P.H., FCCP

Director, Office of Clinical Pharmacology, Office of Translational Sciences
Center for Drug Evaluation and Research

Diane Maloney, J.D.
Associate Director for Policy
Center for Biologics Evaluation and Research

Abigail E. Brandel
Attorney, Office of Chief Counsel
Office of the Commissioner

Richard Klein
Director, Patient Liaison Programs, Office of Special Health Issues, Office of External
Affairs
Office of the Commissioner

Creating an Alternative Approval Pathway for Certain Drugs Intended to Address
Unmet Medical Need
Part 15 Public Hearing

February 4, 2013
FDA White Oak Campus
10903 New Hampshire Ave, Building 31, Room 1503
Silver Spring, Maryland 20993
Each speaker will have 10 minutes for their presentation. There will be 5 minutes
following each presentation to offer an opportunity for the panel to ask clarifying
questions.
February 4, 2013 Presentations
9:00 – 9:10 am Presiding Officer Opening Remarks
Rachel Sherman, MD, MPH
Associate Director for Medical Policy,
Center for Drug Evaluation and Research
9:11 – 9:21 am (9:21– 9:26 am)
Jeffrey Spaeder, Quintiles
9:27 – 9:37am (9:37– 9:42 am)
Roger Echols, Infectious Disease Drug Development Consulting, LLC
9:43 – 9:53 am (9:53– 9:58 am)
Rebecca O’Connor, Parkinson’s Action Network
9:59 – 10:09 am (10:09– 10:14 am)
Jeffrey Stein, Antibiotics Working Group (AWG),
Trius Therapeutics
BREAK
10:14 – 10:30 am
10:31 – 10:41 am (10:41– 10:46 am)
Robert Guidos, Infectious Diseases Society of America (IDSA)
10:47 – 10:57 am (10:57– 11:02 am)
Paul Huckle, GlaxoSmithKline (GSK)
11:03 – 11:13 am (11:13– 11:18 am)
Jennifer A. Jackson, Cubist Pharmaceuticals, Inc.
11:19 – 11:29 am (11:29– 11:34 am)

John F. Crowley, Amicus Therapeutics, Inc.
John R. Kirk, Amicus Therapeutics, Inc.
Jayne C. Gershkowitz, Amicus Therapeutics, Inc.
11:35 – 11:45 am (11:45– 11:50 am)
John H. Powers, George Washington University School of Medicine,
University of Maryland School of Medicine
11:51 – 12:01 pm (12:01– 12:06 pm)
Nicole Mahoney, The Pew Charitable Trusts
LUNCH Ala Carte items will be available for purchase on site
12:07 am – 1:07 pm
1:08 – 1:18 pm (1:18– 1:23 pm)
David Ross, George Washington University School of Medicine
1:24 – 1:34 pm (1:34– 1:39 pm)
Andrew J. Emmett, Biotechnology Industry Organization (BIO)
1:40 – 1:50 pm (1:50– 1:55 pm)
Jonathan Sackner-Bernstein, ExVivos, LLC
1:56 – 2:06 pm (2:06– 2:11 pm)
Alan Solinger, Pharmaceutical Product Development, LLC (PPD)
Association of Clinical Research Organizations (ACRO)
2:12 – 2:22 pm (2:22– 2:27 pm)
Roslyn Mannon, American Society of Transplantation (AST),
University of Alabama, Birmingham
2:28 – 2:38 pm (2:38– 2:43 pm)
James I. Healy, Soffinova Ventures,
National Venture Capital Association (NVCA)
BREAK
2:44 – 2:59 pm
3:00 – 3:10 pm (3:10– 3:15 pm)
Anthony Castaldo, Hereditary Angioedema Association
3:16 – 3:26 pm (3:26– 3:31 pm)
Jennifer Yttri, National Research Center for Women & Families
3:32 – 3:42 pm (3:42– 3:47 pm)

Brian Rosen, Leukemia & Lymphoma Society
Mark Velleca, Leukemia & Lymphoma Society
3:48 – 3:58 pm (3:58– 4:03 pm)
Sally Okun, PatientsLikeMe
David Clifford, PatientsLikeMe
4:04 – 4:14 pm (4:14– 4:19 pm)
Diane Helentjaris, The American Medical Women’s Association (AMWA)
4:20 – 4:30 pm (4:30– 4:35 pm)
Randy Wheelock, Consumer
Open Public Comments
4:36 – 5:05 pm
Closing remarks/Adjournment
5:05 – 5:15 pm

 

[Research 1st]

Thank you for posting this news update JohnnyD. It seemed unlikely the future of Ampligen and CFS would be decided on a Saturday. I am pleased to hear there will be a public hearing, good news I hope for at least a compromise if the drug is not to be approved?

 

[jimells]

This seems like more distraction and delay to me. How many years will they take to 'approve' this new 'pathway'?

"But you don't understand... we have to follow the Rule of Law..."

...except when it's inconvenient, like when it's time to start another war, or kidnap and torture "terrorists", or lock someone up in a military brig without charges or trial, or murder citizens in foreign countries by remote control...

 

[Lynne B]

Hi, Johnny D, This sounds like a good thing to do in general. The trouble is, I don't see anyone on the panel to speak for our medical condition. Also, I think the fact that several of us, such as Bob Miller, have already established how much Ampligen has done for them, so I don't know why that would have to be established all over again before approval was given for them to use it.

regards, Lynne B

 

[JohnnyD]

We'll have to ait and see what Hemispherx says next week. But it appears that ampligen will not get approval this time - it does not fit well with the current approval pathways. The new pathway they are proposing in this seminar, it seems like a very good fit.

While know CFS rep is on the panel - I'm sure this was set up months ago and the timing would not be good if ampligen is rejected - the proposed new pathway is still a fit for CFS.

Lynne B, unfortunately the FDA needs controlled trials to pass a drug. The new pathway proposes, smaller, quicker trials.

They are taling public comments until February 26th. If ampligen gets rejected, which I suspect, we need to convert The Petition drive into a Public Commentary drive to submit as many public comments to the panel as possible.

 

[taniaaust1]

This implies a lot.. it implies they wont currently be able to pass Ampligen as it doesnt mwet the current rules.. so may mean that Ampligen is about to get a big NO .. unless they put the Ampligen approval on hold till they bring this new thing in. As a ME/CFS patient I'd rather see the whole Ampligen decision thing get put on hold till their current rules are sorted out, rather then just a no.

This new drug ruling will be a very good thing and I think WILL happen. Why I think it will certainly happen is cause it will have all those drug companies behind it.. eager to get their drugs out faster. Money makes this world go round one could say..profit, profit, profit.

I think possibly it needs to be pushed that this all needs changing fast and without lengthly meeting delays and I think it appears that is exactly what they want to do as that date... is very very soon. Much sooner then I would of thought if they decided to think about changing things... that date (Feb 4th) could of been in 4-6 mths time..but its almost right away..how often are gov meetings arranged that fast? (i bet not often). So I think they are trying to rush to change things so it appears for once the American gov is trying to do something good for us for a change. (I cant believe Im saying this.. I think this is the first time ever that Ive beleived they are trying to do something for us).

The one big concern I do have thou is why isnt there a ME spokesperson or org who deals with the "severe" patient group..what this new change will be about.. why isnt one going to be speaking at that meeting esp when this new ruling if brought in will help ME/CFS patients greatly? Why are certain patient groups represented and not us??????????????? eg Hereditary Angioedema Association, Parkinson’s Action Network, American Society of Transplantation, Infectious Diseases Society of America, Leukemia & Lymphoma Society (they actually have 2 of their spokespersons talking, so a double time slot)

Are the gov still trying to "play it safe" and dont want our illness to be seen as a serious one.. not serious enough to have representation for our severe patient group at this very important meeting????. I think some new advocacy efforts are needed right now.. to email those responsible for this meeting and ask WHY arent the severe ME/CFS patient group being ignored at this meeting with no representation for us there. I propose that if they dont give ME/CFS a serious representation for the severe patient group of ME that ME/CFS patients should use that meeting as a PROTEST opportunity to protest how this illness is being IGNORED, with the very sick patients going invisible.

Please those in America.. please protest outside this meeting if you can if we dont get some decent spokesperson there on severe ME.. (you dont need to be protesting with others to do a protest... whether its just one protestor or many.. we need to protest at that meeting if our illness is ignored). Dont allow this ignoral of ME/CFS patients go on..BE SEEN. (Not long ago I had a laying down protest .. I actually feel asleep during it at a medical conference which was ignoring ME/CFS).

I hope our well known ME/CFS advocates hear about my idea for a protest there in regards to once again this illness being ignored and will call up a protest there.

 

[Shell]

I'm afraid I too think this looks like stalling. When you consider how many vaccines and other drugs get approval without this much faffing about and with far less understanding of how they work.

Let's take Clozaril for example. It was approved back in my day (1980s) even though it was well known to have truly horrible side effects. It was such a toxic drug that patients on it had to have 3 monthly then 6 mthly bloods taken. We would get a report back from the lab marked as "green" meaning carry on, "amber" meaning things looked bad and "red" meaning patient had to be taken off the drug.
Lots of patients with intractable forms of pychosis, particularly scizophrenia were put on this drug and it helped a lot of them (though not all by any means)

And yet for Ampligen the goal posts don't so much move as race around dodging the ball.
Is this political by any chance? Is this a fear that by approving it the FDA are admitting the CDC were pillocks of the first order and this isn't all in our silly female heads?

 

[LaurelW]

Anybody know if this meeting will be webcast and if we can watch it? I didn't see anything about that on the link.

 

[Ember]

I propose that if they dont give ME/CFS a serious representation for the severe patient group of ME that ME/CFS patients should use that meeting as a PROTEST opportunity to protest how this illness is being IGNORED, with the very sick patients going invisible.

Who would represent "the severe patient group of ME?" With reference to CFS, how would "a smaller subpopulation of patients with more serious manifestations of [the] condition" be defined?

 

[Waverunner]

I remember, that NICE approved a Multiple Sclerosis drug although it didn't pass their evidence based requirements. The reason they approved it was, that until then there was no treatment for MS and they wanted to give MS patients at least some form of hope. Maybe this applies here too.

 

[taniaaust1]

Who would represent "the severe patient group of ME?" With reference to CFS, how would "a smaller subpopulation of patients with more serious manifestations of [the] condition" be defined?

i didnt word that well did I. Ive not a clue but as they are refering to severe "subgroups" of illnesses and approval for just subgroups of illnessses.. how to define those things?? ..which groups would qualify under a policy change and which ones wouldnt. ... that would be up to them.

Those who arent very sick should they be approved to trial dangerous or life threatening drugs?? The severity of each individuals illness needs to be well weighed up with the risk of the drug. Should someone who has ME/CFS but can still work full time.. be given an experimental drug which kills off one type of cells or carries a very high risk?? At this point of research..where there isnt a lot of current research.. should dangerous drug recommendations be only made to homebound or bedbound patients or to all?. Wouldnt it be irresponsible thou if dangerous drug recommendations without a lot of research behind them were being recommended to those not so sick? (not housebound or bedbound).

Why should the completely bedridden ME/CFS ones be denied drugs on the grounds it is too much risk (as what is happening now).. as they may be too much risk for one not as disabled by the illness if one weighs up risks verses possible benefits. Currently severe patients get left to like rot.. and cant get the more risky treatments they may need. eg I cant get the saline IVs I need, I'd like an indwelling catheder put in if saliva IVs helped where are this risk wouldnt be worth the risk for many others. ..most ME/CFS info doesnt even mention daily saline IVs. Why? cause the risks" for most" outweigh the benefits. Does that mean that it shouldnt be approved for those who need them? The severe group of ME/CFS which needs more risky treatments currently misses out. There is currently an imbalance going on.

I'd actually thou also like to see medication approval rather based on what kind of symptoms people get then severity (as I actually think ME is happening in all kinds of severity with some more minor cases) eg those showing more viral symptoms eg fevers, sore throats, swollen glands, coughing etc should have a chance to trial antivirals etc. But anyway.. things need to start somewhere with some meds of different types starting to be approved for our illness. Let us tral things till science sorts itself out. (actually with patients trialing things and the severe groups trialing more high risk drugs.. it may actually help science faster realise what is helping patients and what isnt

As far as who could represent the sicker ME/CFS group... as I dont live in America I cant say as I dont know the ME/CFS groups there well enough but I do know there is some orgs there who tend to "play down" the serious of our disease and hence wouldnt be very good supporters of the completely bedridden patient group. Here in Australia we have the Alison Hunter Memorial Foundation who represents the very sick group and helps highlight just how severe some ME/CFS patients can be and who has had a big impact on things here over the years... they help educate doctors, have at times run and funded ME/CFS medical conferences etc etc.

 

[taniaaust1]

I'm afraid I too think this looks like stalling. When you consider how many vaccines and other drugs get approval without this much faffing about and with far less understanding of how they work.

Let's take Clozaril for example. It was approved back in my day (1980s) even though it was well known to have truly horrible side effects. It was such a toxic drug that patients on it had to have 3 monthly then 6 mthly bloods taken. We would get a report back from the lab marked as "green" meaning carry on, "amber" meaning things looked bad and "red" meaning patient had to be taken off the drug.
Lots of patients with intractable forms of pychosis, particularly scizophrenia were put on this drug and it helped a lot of them (though not all by any means)

And yet for Ampligen the goal posts don't so much move as race around dodging the ball.
Is this political by any chance? Is this a fear that by approving it the FDA are admitting the CDC were pillocks of the first order and this isn't all in our silly female heads?

I think it is certainly politics that one of our representives arent talking at that policy change meeting. They probably dont want to highlight the ME/CFS situation in any way at all.. its an burial.

 

[taniaaust1]

I remember, that NICE approved a Multiple Sclerosis drug although it didn't pass their evidence based requirements. The reason they approved it was, that until then there was no treatment for MS and they wanted to give MS patients at least some form of hope. Maybe this applies here too.

Maybe things could lead then to a group legal case .. group discrimination if they knock Ampligen back . Could enough evidence be put together to show that gov decisions are being made biased towards ME/CFS?

 

[Ember]

I'd actually thou also like to see medication approval rather based on what kind of symptoms people get then severity (as I actually think ME is happening in all kinds of severity with some more minor cases) eg those showing more viral symptoms eg fevers, sore throats, swollen glands, coughing etc should have a chance to trial antivirals etc. But anyway.. things need to start somewhere with some meds of different types starting to be approved for our illness.

According to the FDA proposal, “the drug's safety and effectiveness would be studied in a smaller subpopulation of patients with more serious manifestations of a condition.” So the FDA is already looking for serious (not just severe) manifestations of the condition.

In her FDA presentation at the October CFSAC meeting, Dr. Sandra Kweder said that “a research definition is needed so that we can begin to study things.... The only way you learn is by starting someplace. Clinical therapeutics are not going to be developed until this is done:”

Chronic Fatigue Syndrome

We have some real challenges with Chronic Fatigue Syndrome:

• The heterogeneity of symptoms evidenced in the difficulty and controversy surrounding development of disease criteria.
• Limited objective measures. The pathophysiology of the conditions is not well understood. There are no well established biomarkers.
• Clinical trials and drug development in this field that have been constrained by these factors.

It’s not because nobody cares about this condition. It’s because there’s so much uncertainty....

Ampligen (rintatolimod) injection has a small database of controlled data. The drug was not approved in 2009, it was resubmitted in 2012, it’s under review right now, and it has a goal date for a decision in early 2013.

Why So Few Applications?

It’s because the core is still in question:

• No accepted definition for the disease, and controversy besides.
• No accepted method for measuring how patients with CFS or ME feel or function.
• No accepted biomarker to provide a simple, quantitative measure of disease presence or activity....

I can give you examples of what has happened in conditions that have had absolutely the same challenges:

• Irritable bowel syndrome (IBS)
• Functional dyspepsia
• Depression
• Prostate cancer
• Fibromyalgia (FM)

All of those conditions have the same problems. All of them have new methods of study and growing therapeutic armamentariums because a generally agreed‐upon definition with signs and symptoms and measurement tools that can be employed for that condition were agreed upon and developed. Then there was able to be a movement forward. I didn’t think I’d live to see the day when people could agree on IBS. There are three approved, marketed drugs for FM. That is absolutely amazing. Progress can be made by defining the condition, particularly for the purpose of clinical trials.

What Should HHS Do?

Use every tool possible to facilitate defining the condition for research purposes in a way that can be widely agreed upon:

• Include all parties with expertise and interest in this condition.
• Include patient representation in the consensus. Consensus doesn’t mean that everyone has to agree on every point. Consensus means we can move forward.

A research definition is needed so that we can begin to study things. It may be subject to change over time. That’s OK. The only way you learn is by starting someplace. Clinical therapeutics are not going to be developed until this is done.

HHS needs to invest in tools to specifically measure symptoms, signs, and function of the CFS and ME populations. We are very willing to work with those groups that may be funded or be charged with developing those kinds of tools. Through the department, we should partner with organizations and centers that are equipped to conduct clinical trials.

The ICC already identifies a smaller subpopulation of patients with "more serious manifestations of the condition."

 

[Ember]

Anybody know if this meeting will be webcast and if we can watch it? I didn't see anything about that on the link.

Webcast Update:

For those unable to attend in person, the meeting will also be shown via webcast. Watch the webcast on February 4th from 9:00 am to 5:15 pm. Requirements and instructions for accessing the webcast are below. Please be sure to download the most up-to-date version of Flash Player.

You may access the webcast via this link: https://collaboration.fda.gov/altapprovefeb2013/.

Adobe Connect Minimum Requirements

• View meetings on Windows, Macs, Unix, and Linux platforms
• Lan or Broadband internet connection
• Supports Internet Explorer, Firefox, Safari, Netscape Navigator, AOL
• Adobe Flash Player (no other downloads needed)
• VPN and Parachute compatible but not required
• Test my computer for Adobe Connect-Readiness

Either electronic or written comments will be accepted after the hearing until March 1, 2013
(https://www.federalregister.gov/art...-drugs-intended-to-address-unmet-medical-need):

Interested persons may submit either electronic comments to http://www.regulations.gov or written comments regarding this document to the Division of Dockets Management (see ADDRESSES). It is only necessary to send one set of comments. Identify comments with the docket number found in brackets in the heading of this document. In addition, when responding to specific questions as discussed in section III of this document, please identify the question you are addressing. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

III Scope of the Public Hearing and Discussion Questions

FDA is holding this public hearing to seek input from interested members of the public including patients and consumers, practitioners and other members of the medical community, regulated industry, insurers, and managed care organizations on a potential new pathway to approve drugs shown to be safe and effective in a subpopulation of patients with serious or life-threatening conditions in which an unmet medical need exists. FDA is interested in obtaining information and public comment on the following issues:

1. Considering existing processes to expedite drug development and review of important new therapies (i.e., accelerated approval, fast-track designation), would this new pathway increase the therapeutic options for serious or life-threatening conditions for which an unmet medical need exists? If not, what might be some alternative approaches?

2. Can you identify specific serious or life-threatening conditions for which an unmet medical need exists and for which this approval pathway may benefit subpopulations of patients?

3. What approaches could be undertaken (by FDA or by people or organizations other than FDA) to monitor use of drugs approved under this pathway to determine whether they are being used inconsistent with the terms of approval? What approaches could be undertaken to prevent, manage, or monitor use in a broader population where safety and efficacy has not been demonstrated? For example, if this pathway were adopted to approve new antibacterial drugs when limited use was needed (e.g., to prevent the emergence of further antimicrobial resistance), what other measures (by FDA or by people or organizations other than FDA) might ensure that these products are used appropriately only in the indicated subpopulations?

4. Would this pathway help to address some of the current challenges in antibacterial drug development, particularly for serious or life-threatening infections for which there is an unmet medical need?

5. This potential pathway could be used to approve drugs for a limited subpopulation based upon smaller clinical trials, when benefit-risk is appropriate for the limited population but safety and efficacy have not been demonstrated for use in a broader population of patients or patients with less severe manifestations of the condition. For the serious or life-threatening conditions you identified in question 2, what benefit-risk considerations need to be taken into account before and after marketing and how should they be addressed?

6. Would the use of a formal designation and logo to reflect approval under this pathway, with clear labeling of clinical information that only supports use in the indicated subpopulation, but without other constraints from FDA be effective in limiting use to the indicated subpopulation? Why or why not?

Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

I can't find the docket number for identifying comments.

Transcripts of the public hearing will be available for review on the Internet at http://www.regulations.gov approximately 30 days after the public hearing.

 

[JohnnyD]

Speculation on my part. Regarding identifying sub-groups and those severely afflicted. I think this is what the CDC has been doing with their multi-site clinical assessment. They started this assessment in July, posted to webiste in November, results are due this month or next I believe. From CDC website.

"Ultimately, this study aims to improve how we measure illness domains of CFS. This may allow patients to be sub-grouped to improve therapy and allow the underlying biology to be discovered."

This new pathway hearing has obviously been worked on for months, but only posted the the public register on Jan 15. I see lots of positives. Regarding having a seat at the table for this public hearing. I cannot think of another disease, besides CFS, that meets the criteria. The problem with current FDA pathways with such a large population as CFS is the larger phase III trials required. A thousand patient trial of CFS patients would be extremely difficult... for any drug maker large or small. So from the hearings description, IMO, CFS IS the table. The FDA has a stakeholder scheduled for Spring. If they reject ampligen this time around (likely), This gives them a way forward and they might actually get someone to show up at the stakeholders meeting. I mean besides protestors. They need to attract drug makers and they need a way to get ampligen approved with out some long drawn out large phase III trial. It means patients have to wait yet again, but this is a way forward.

 

[Sasha]

Very interesting!

 

[JohnnyD]

The word is that HEB received a 70 page CRL from the FDA late Friday afternoon. HEB is preparing their response/PR which will probably be released this afternoon.