FDA Drug Development Workshop: Part Two

Gabby (Nielk) continues our summary of the FDA Workshop with a look at the second half of Day One – a discussion entitled “Patients’ Perspective on Treatment Approaches”

FDA Workshop 3The FDA Drug Development Workshop for chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) took place on the 25th and 26th of April 2013. It was well attended by patients, advocates, doctors, representatives of the CDC and even a few pharmaceutical reps.

The workshop was also broadcast live over the internet, enabling many more people to follow what happened without being there in person. This meeting was an opportunity for us to be heard, and continues to be an opportunity as comments can still be added to the docket until August 2nd 2013.

The FDA have clarified that they will accept video submissions in the form of links to YouTube videos – allowing the sickest and most disabled patients, who were unable to attend the workshop, to have their say. You can submit written comment on the docket (2,000 word limit), attach a Word or PDF document, or include a link to a YouTube video.

This is the second in a series of articles about the Workshop which attempt to summarize 85,000 words of talk over two days into only a few thousand words. Part One can be found here. Part Two covers the content of the third video of the workshop.

Day One, Part Two: Patient perspective on treating CFS and ME [video three]  [transcript]

Moderators: Sara Eggers, Ph.D. and Theresa Toigo, R.Ph., M.B.A.

The following questions were posed to the panel:

  1. What treatments are you currently using to help treat your condition and its symptoms?
  2. How well does your current treatment regimen treat the most significant symptoms of your disease?

PANEL COMMENTS

Mary Dimmock – Mother of 25 year old son ill for three years [Timestamp 03:00 – 06:25]

Mary Dimmock
Mary Dimmock

Before finding an ME specialist, doctors dismissed Mary’s son’s problems or ill-advised him to exercise in a gym which rendered him bedbound for days.  Today, he is largely housebound, spending a lot of time lying flat while listening to audiotapes.  When they finally found an ME specialist he was prescribed Immunovir for low NK cells, Florinef for O.I., sleep meds for unrefreshed sleep, antivirals for high viral titers, anti-fungals for Candida and an activity program to address PEM by strict pacing.  He was told to stay away from sugar, alcohol and coffee.  He was also put on regimens of antibiotics for Lyme disease.  Only two treatments made a difference. 1- The combination of antibiotics for Lyme increased his capability to get around.  He could go out for five hours at a time and read many books a week.  Unfortunately this only lasted for six weeks.  Despite a full year of IV, IM and oral antibiotics treatment, the improvement never returned.  2- The drug Kineret, prescribed for high IL1, brought about an improvement in NK cells and normalized his neurotransmitters but with little functional change.  Rituximab has been recommended for him but, without FDA approval, the cost is huge.  Despite having great doctors, good medical insurance, a supportive wife and family, he feels like he has no hope.  “He is willing to accept risks with new treatments, trying anything to give him back his life to escape this hellish disease,” Mary says.

Tasha K. – Patient with ME since 1996  [Timestamp 06:25 – 14:00]

Tasha contracted a tropical infection in 1996 in Angola, Africa while working there.  She has the unique experience of living with this illness in three different countries: Belgium, U.K. and the U.S.  Her first symptoms were those of sore throat, fever and severe fatigue. She lost 22 lbs in 2 months. She had a rash on her arms.  She noticed in particular that her symptoms became aggravated after exercise. In Jan. 1999 she moved to the U.S and was diagnosed with CFS.  She was working part time and her condition became cyclical with better periods and then crashes.  In 2000, they isolated the tropical infection which she contracted in Angola and she was treated with antibiotics. This brought about a great improvement in her condition. She was able to work full time for the next 3 years.  In June 2003, 3 months after giving birth to her daughter, she became very sick again. She was living back in the UK and was accepted as part of the PACE Trial.  She chose graded exercise therapy because she wanted the help of Physical Therapists to do gentle stretching exercises.  The GET improved her condition slightly.  She never saw any CFS specialists in the U.K., unlike what the Pace Trial authors claim.  She says that the problem in the U.K. in general and the Pace Trial is that they only look at one symptom of CFS – fatigue – and ignore the rest of the symptoms.  She moved back to the U.S. where she started on B12 shots and then Valtrex.  Now, she has been switched to Valacyclovir which along with B12 shots and Cevela have enabled her to start working part time again.  She says “the idea that all symptoms come from deconditioning (per UK), and that exercise along with overcoming negative thoughts patterns is the answer, is ridiculous and offensive.”

Matina Nicholson – Patient with ME for six years – mostly homebound [Timestamp 14:00 – 19:40]

Matina Nicholson
Matina Nicholson

Matina used to be a senior manager in marketing at a pharmaceutical company. She has a lot of significant cognitive and neurological problems with no effective treatment options.  For her PEM/PENE issues, she takes Adderal as needed.  For her auto-immune symptoms, she gets bi-monthly infusions of Meyer’s cocktail and monthly shots of Immunoglobin.  In addition, she self injects vitamin B12 and Glutathione. She takes the supplements Levocarnitine and vitamin D.  For sleep, she takes Ambien and Xanax.  Pain is treated with Cymbalta or Vicodin and a heating pad.  These are all just for symptom control. She can’t afford IVIG which has not been approved for her from Medicare.  For the following issues, she has not found any effective treatments: gut issues, low NK cells, high EBV, HHV6, CMV titers, cognitive dysfunction.  She adds, “I’d like to focus on research about cognitive rehabilitation therapy which is done for MS, Lyme and Lupus.”  The side effects of some drugs are hard to deal with.  Adderal, which she has to take when she needs some function, renders her with dry mouth, the jitters and unable to sleep.  If she takes more than 10 mg of Ambie, she will go out to drive without realizing it.  Finally, she asks the FDA to fast track drugs for this complex disabling illness.

Mary Schweitzer – Patient with ME for 14 years mostly on Ampligen [Timestamp 19:50 – 25:00]

Mary Schweitzer
Mary Schweitzer

In 1994, at age 44, while working as a professor of history at Villanova Universty, she suffered a blackout. Subsequently, she suffered from more blackouts, ataxia, short term memory loss, dyslexia and massive confusion,  to the point where she says, “I poured coffee into a silverware drawer convinced it was a cup”. She suffered from intense headaches with pain behind the eyes and at the back of the neck.  She was treated with Levothroid for hypothyroidism and with Florinef for NMH/POTS with no success. For sleep problems, she was given Flexeryl, Ambien and Klonopin.  This made her somewhat more comfortable but her condition kept getting worse.  By 1996, she was falling all the time and could not drive anymore.  By 1998, she became totally bedridden.  At that time, Dr. Ablashi tested her and found that she had HHV6 – variant A.  In addition she was found positive for 37kDa Rnase-L Factor which is a predictor for success with the treatment of Ampligen.  Her family decided to go through the great expense for her to receive treatment with Ampligen, even though it meant moving away from her family.  After two months, Mary was walking again.  At five months, she was driving. For the first time in four and a half years, she did not feel sick anymore.  The stamina took longer to build up.  Twenty months later, feeling well, she stopped Ampligen because it was so expensive.  A year later, she started blacking out again and the HVV6-A was back again. It took a few months to get back on it and longer to gain back her strength.  Since then, Mary has been off and on again on Ampligen. Today, she has to travel twelve hours twice a week in order to get Ampligen at her own cost from Dr. Enlander’s office in NYC (from Washington DC).  Now, she has the added stress of taking care of her husband (Bob) who is fighting an aggressive form of cancer.   “It’s that important that I remain on Ampligen.  Without it, I would not be here talking with you.  Without it, I would not have a life”, Mary implored.

Amanda Simpson – Patient with ME for 3 years [Timestamp 25:10 – 30:05]

Amanda Simpson
Amanda Simpson

Three years ago, within a period of three weeks, Amanda had to put her dog to sleep, her father was diagnosed with cancer and her husband died in a car accident.  Four months later, she had to go to the ER with the flu. It took thirteen months, thirty doctors across Dallas, Houston, Los Angeles and New York for her to get a diagnosis of ME/CFS.  She takes 16 pills a day and two injections a week.  She takes Sevela for pain and energy which helps her stay out of bed.  She also takes Tylenol and Hydrocodone as needed for pain.  For sleep, she takes Zolpidem.  For her immune system issues, she takes injections of Hepapressin and Nexavir along with Immunoprop and immun pro plus from Dr. Enlander. Her supplements consist of a multi-vitamin, fish oil, vitamin C and D.  Last year, she started taking GcMaf and saw a decrease in her symptoms of weakness, pain, brain fog, sore throat, sensitivity to light and sound.  She is seeing an increase in energy.  Her levels of EBV and HHV6 have decreased too.  She has used acupuncture as well as chiropractic treatment for headaches, pain and sleep disturbance with some success.  The downside of all these medicines is all the side effects that come with it.  Her medical care can cost as much as $2,500 a month. (!!!) She adds, “I can say, although I’m not as well as I’d like to be, these treatments have restored a great deal of purpose and meaning to my life..and so I’m in the process of trying to start a non-profit organization to help speak up for those with this illness who can’t speak for themselves.”

BROAD DISCUSSION – audience participation [Timestamp 32:00 – 71:00]

Ampligen experiences  [Timestamp 32:50 – 39:30]

Jeanette –   After a stress test (treadmill test) two weeks ago, she crashed with symptoms flaring up, including pain, G.I.problems and sleep problems.  A couple of days later, she dragged herself to her Ampligen infusion.  After which, she was bouncing out of the office with an immediate huge improvement!  [Timestamp 33:00]

Janet – Was helped for three years with Gamma globulin shots for her IGG deficiencies.  Then it started declining and she had to do something drastic.  She started traveling from South Dakota to Incline Village and Dr. Peterson weekly to get Ampligen. At first, she couldn’t walk up the jet way. Today, she has two practices going and she wouldn’t be here if it wasn’t for Ampligen.  [Timestamp 34:33]

Robert – He is a patient since 1982.  Before Ampligen, he was bed-bound.  “When people talk about being bed-bound, we are like bricks – we can’t be moved,” Bob says. Dr. Peterson enrolled him in the Ampligen clinical trial in 1998. As far as his energy level and cognition goes, he says, “for me, it was like a little glimmer of light that I could feel and see again.”  Prior to Ampligen, he was placed on Famvir, Valtrex, Valcyte, Zithromax, Amoxicillin, Prozac, Lyrica, Cymbalta, Pameral, Flexeral. Before Ampligen, his NK cells were down to zero and his T-cell count was 285.  With Ampligen, it’s five times that.  He has been off and on Ampligen.  When he went off, he slid back to the state he started from.  He sold everything and moved back to Reno to get Ampligen from Dr. Peterson.  “For any medication to get me up and allow me to think clearly, allow me to function, allow me to make my own meals, allow me to go outside with my boys, is a miracle,” Bob says.    [Timestamp 35:29]

Other treatment experiences: treating the underlying illness [Timestamp 39:35 – 43:15]

Lilly – She wants everyone to know that these costly treatments are only available to a very select few of ME/CFS patients.  It is only those with good insurance, money and supportive families who support them in order to get to these places and treatments. (Great point!!!)  [Timestamp 40:00]

Carol – She got sick 28 years ago in Denver as part of an outbreak. The most helpful drug for her has been Vistide, prescribed by Dr. Peterson. It’s a very potent antiviral HIV/AIDS drug.  On Vistide, she can think clearly, function and she has lost weight.  She states, “You can also see this is a biological disease that has physical cause when something affects it so profoundly.”  She is also currently taking GcMaf with some success.  [Timestamp 40:32]

Pain Management Treatments  [Timestamp 43:45 – 57:55]

There was lot of discussion about all different types of anti-depressants like Cymbalta, Lyrica, Flexeril.  Most said that it didn’t help at all.  Others had minimal relief.  The issue of side effects was raised as well as the difficulty with trying different options to see which one might work.  One needs to be on it for two to three months to see any effect.  There is also the issue of it losing effect after a time.  To some, they need to balance the effectiveness of pain management with the issue of side effects like worsening of cognitive issues.  It comes down to “the pain management versus brain fog” dilemma.  There is also the fact that many have G.I issues to begin with and these drugs may exacerbate these symptoms.

Medical marijuana was brought up as an option for pain.  Studies have shown that it is effective for pain as well as sleep issues. 

A mother mentioned that her daughter, who got ill when she was fourteen, was prescribed Oxycodone and Percocet for pain by her doctors when she was only 18.  She wound up with esophageal ulcers after a few years!  She has been on pain medications for 22 years. She now needs to go to rehab to get off these drugs.  She is completely disabled now. “It’s a nightmare”, the mother said.

The issue that was brought up is that this is a chronic illness that persists for many years.  It is dangerous to take these hard core pain medications long term, which are meant for acute problems.

Mention was made that some patients with ME/CFS feel nerve pain which might be helped with antivirals.

A patient stated that she thinks her pain can be attributed to lack of oxygen because of her shallow breathing which causes muscle pain.

There is the debate whether all these medications that deal with symptom relief really work and how the side effects might make things worse.  In addition, some say that by “masking” the symptoms with these drugs, they feel that they might overdo things and cause a relapse.  Are less drugs better?

Physical Therapy and Pacing  [Timestamp 57:55 – 61:33]

Some are helped by pacing and staying within their “envelope” of activity. Some use a heart rate monitor to help them limit their activity. Very light physical therapy with stretching exercises while lying down is helpful, some say.

I.V. Saline Drip  [Timestamp 61:48 – 63:50]

IV saline drips are helpful to some for light-headedness and low blood pressure. It is relatively low cost.  Someone mentioned that oral salt and water could be effective in an emergency.

OPEN PUBLIC COMMENT

Moderator – Theresa Toigo

Anita Patton  [Timestamp 75:00 – 77:08]

Anita says that doctors should get together for research effectiveness and devise ways to find subsets of patient groups.  Some had slow onset and others had sudden onset to their illness.  Some have low NK cells or high cytokines.  It’s important to identify who the responders are for different treatments.  She is an Ampligen responder for fifteen years and is disappointed it wasn’t approved.

Dr. Janet Smith (standing in for Courtney Miller)  [Timestamp 77:30 – 78:30]

She is on the board of The Simmaron Research/Dr. Peterson Foundation.  They are working to scientifically redefine ME/CFS.  She was pleading with the FDA to apply to ME/CFS the same looser rules that they have applied to Alzheimers for drug approval.

Judy Mikovits  [Timestamp 77:30 – 78:30]

Judy says that MS, Parkinsons, Lupus and ME/CFS are all serous debilitating diseases with no known cause.  They each share abnormalities of the immune system and inflammation.  The FDA just approved Dimethyl Fumarate, an immune modulator and anti-oxidant, for the treatment of MS.  In Norway, oncologists completed a small study of FDA-approved cancer drug, Rituximab, with success in 30% of patients.  “The next logical step to do with Rituximab as well as Ampligen is gene expression and immune profiling to determine the difference between responders and non-responders at the molecular level”, she states.  She encourages funding to be raised for these clinical trials“It’s a new era for ME/CFS treatment,” she stated. She says that the FDA has recently given ME/CFS the classification of a serious disease without treatment. “The technology and expertise exist”, Judy states.

Derek Enlander  [Timestamp 82:08 – 84:05]

With a million dollar grant from a patient, Dr. Derek Enlander started the ME/CFS Center at Mt. Sinai in New York.  Their first project is to prove whether GET was appropriate for this disease.  They expect to look at 150 patients and 150 controls, researching PEM.  They are looking at all cytokines and immune markers.  With Dr. Eric Schadt, a well known geneticist, on board, they are looking at genetic studies comparing ME/CFS patients to healthy controls.  They already have a series of 39 page genome studies on their first patients.

Gisela Morales Barrelo  [Timestamp 84:10 – 87:35]

She is a doctor and caregiver of a patient with M/CFS. She says that it has not been easy to watch a person who used to move with the speed of light, be limited to bed for days, months and years.  Gisella is a cancer survivor.  At least with cancer, there are options for treatment, she says. She is here at twelve years and knows, if she were to get sick again, she can get back on treatment.  “For me,” she adds, “the big elephant in the room, after everything has been said, is the fact that we need pharmaceutical companies.”  The FDA can only approve something that the pharmaceutical companies present.

Thomas Equels  [Timestamp 88:00 – 92:00]

Thomas is the executive vice chairman of Hemispherx, maker of Ampligen.  Hemispherx was asked 30 years ago, by the FDA, to come to Lake Tahoe where Drs. Peterson and Lapp were treating patients from the outbreak there, he says.  They treated, experimentally, a woman who had a remarkable recovery, and twelve more patients with success.  It has been a long difficult journey for a company as small as his.  There is an unmet need here and subsets of patients need to be identified.  He concluded by saying: “Now we’ve expanded a great deal of time and money to get where we are today and I just want to say we’re prepared to enter into a real partnership with the FDA, with the clinicians and with the patients to bring relief for people who so deservedly need it.”

Dan Peterson  [Timestamp 92:25 – 95:45]

Dan has had experience taking care of 9,000 patients in thirty years. He says that the CDC has identified one million people in this country with the disease. The estimated cost to our country is believed to be nine billion dollars a year. A diagnostic marker would yield a company 250 million a year and a therapy probably in the billions of dollars. Over twenty five years, there has been no approval of any drug or therapy.  The problem of the patient group being heterogenous needs to be addressed.  There have been thousands of published peer reviewed articles with respect to pathogenesis.  There have been a few biomarkers such as low NK cells, abnormal brain MRI and spect scans, and low VO2 on stress tests.  He states: “symptomatic therapy, unfortunately I think, is useful in quality of life, but I have not seen it return patients to full function, physical or cognitive.”  He believes, though, that targeted immunological therapy has a possibility to do that. He mentioned the recent establishment of a worldwide consortium and collaboration with multi-primary care clinics that are ready and willing to do pilot projects, phase I, II and III clinical trials, and more. 

Eileen Holderman  [Timestamp 96:20 – 98:30]

Eileen is an independent advocate.  Her concern is with the name of the conference, using CFS instead of ME.  She says that in 1988, the CDC renamed this disease Chronic Fatigue Syndrome with an empirical definition which just states one symptom: fatigue.  This has caused muddy research, no universal biomarkers, no drug development, bad media and press.  “The solution,” she states, “is that all the government agencies, the scientific medical community, legal advocates and patient communities must come together and adopt the Canadian Consensus Criteria and dismantle the use of CFS.”

James Baraniuk  [Timestamp 98:40 – 101:45]

James says that they started publishing the results of their studies from Gulf War Illness patients who also met the criteria of Chronic Fatigue Syndrome.  They identified changes in FMRI due to exercise. The changes appear with white matter abnormalities.  They have also identified subgroups based on blood flow responses due to exercise-induced exertion. He states that “We are going to have objective diseases that end up in the Harrison textbook of medicine.” 

Charles Lapp  [Timestamp 102:10 – 104:08]

Charles is a physician from Charlotte, North Carolina.  He has treated patients with CFS since 1985.  The past 25 years, he has used Ampligen with excellent success.  He says that 50% of his patients have responded very well to Ampligen and 30% have significant improvement.  He has not seen any serious side effects in his patients taking Ampligen.  He says that when other new drugs are bought into the field, like AZT for AIDS and Interferon for MS, many other players/pharmaceutical companies came in to the field and opened up treatment for these two diseases.  “We hope that Ampligen will do that for Chronic Fatigue Syndrome”, he states.

Steven Lempert  [Timestamp 104:15 – 106:38]

Dr. Lempert cites the paper by Dr. Ablashi regarding Ampligen inhibiting HHV-6 by 46% to 98%. He said that group of severely ill CFS patients are positive for active HHV-6A.  Mary Schweitzer, who was positive for HHV6-A before Ampligen, was found free of it when tested three times while on Ampligen.  He suggests that Ampligen should be transferred to the FDA antiviral division and re-evaluated now, rather than wait another ten to twenty years.

Joan Grobstein  [Timestamp 106:38 – 108:38]

Joan is a physician who has had ME for fourteen years.  She points out a few important issues for the FDA to keep in mind.  Regarding the issue of defining the patient population, she suggests the Canadian Consensus Criteria.   The validation of biomarkers is essential. There are already measurable abnormalities.  She continues that it’s important to treat the underlying cause of ME.  She states: “It’s very likely that multiple agents will have to be used to treat this multi-system disease.”

Jeanette Burmeister  [Timestamp 108:52 – 110:52]

Jeanette is urging the FDA to put Ampligen on an accelerated track for approval.  She says that there is a double standard at the FDA regarding Ampligen and CFS.  A new drug was just fast tracked by the FDA for Tuberculosis.  She says that Hemispherx is running out of money and Ampligen might go away.

Mindy Kitei  [Timestamp 111:00 – 113:52]

Mindy is a science reporter and blogger at CFS Central.  In 1994, she wrote an investigative piece for Philadelphia Magazine called “The AIDS Drug No One Can Have”, about the experimental drug Ampligen.  Mindy is very upset about the fact that much of the data on this disease is based on studying patients with the wrong criteria.  Instead of taking patients based on the Canadian Consensus Criteria or the ICC, they have been studying patients based on the Fukuda or Empirical criteria, as per the CDC and before that the NIH. She says that the Fukuda, the new revised Fukuda known as Empirical, as well as the Holmes and Oxford definitions are all wrong!  She says this is like doing an HIV trial where none of the patients are positive for HIV.  Because of this problem doctors are misinformed. She states that Dr. Lisa Corbin tells her patients to pace by telling them “Monday is for mending, Tuesday is for ironing…”.  Five of the patients Mindy interviewed in 1994 have since died.  One was a close friend of hers; three were in their forties and fifties. “Do you really think that that these patients would be alive if only they had done their mending on Monday?”, she concludes.

Don Kalns  [Timestamp 114:00 – 116:40]

Don is not a CFS or ME person.  He works for a biotech company which has worked on an application to study saliva for fatigue.  The US army has been interested in their work because of fatigue being a major problem with their soldiers.  They recently did a small study with archived saliva from CFS patients.  “We need your spit” he stated…to do more studies. (Laughter in the audience)

Dianne Lewis  [Timestamp 116:00 – 120:55]

Dianne is a licensed certified social worker, clinical therapist and suffers from ME.  She says CBT doesn’t work. She does use hydrotherapy with some relief. She works in a hospital part time.  She will work one day for four hours and then she will need to have complete bed rest for the next two days. She says the doctors in her hospital don’t understand.  They tell her “we don’t treat this disease here”.  It is only when she completed studies with Dr. Peterson and Dr. Lapp and she brought back the results that they looked at her seriously and prescribed medications to deal with her symptoms.

 

Coming soon: In the next article in this series, we’ll move on to day two of the workshop – the Drug Development Scientific Workshop.

 

Gabby is a patient with ME/CFS – disabled since 2003.  She is passionate about raising awareness of the plight of severe sufferers of this disease.

 

 

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