Another trial for Ampligen

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Twenty patients begin use, could expand to 100

This article is reprinted with permission from The CFIDS Chronicle, Vol. 10 No. 3, Summer 1997.

The makers of Ampligen, the most promising drug for treating chronic fatigue and immune dysfunction syndrome (CFIDS) in the Food and Drug Administration (FDA) pipeline, received permission in May to conduct a small, open-label clinical trial for severely debilitated patients. Meanwhile, the FDA and HemisphereRx Biopharma will develop a protocol for a Phase III clinical trial to begin by the end of this year.

This open-label program, called the 511 trial, will consist of just 20 patients taking the drug twice per week for 24 weeks on a cost-recovery basis, meaning the patients must pay for the drug and doctor’s fees. The drug alone will cost about $6,900 per patient.

HemispheRx Biopharma CEO William A. Carter said the original protocol was written for 100 patients. FDA consumer safety officer John Mahoney said the agency will decide after 20 patients are enrolled if the trial can be expanded.

A possible reason for delay in full approval for the trial is that data collected since May 1993 from a trial in Belgium have not yet been given to the FDA. An interim analysis of the Belgian study was presented at the AACFS conference last year, but Carter said data were still being analyzed.

A company press release said the pricing would enable HemispheRx Biopharma “to recover cost of manufacture, research, development and handling of the expanded acess program.” Carter has said Ampligen has cost the company more than $100 million to develop.

Some CFIDS patients are angry about the high cost. Said Gayle Babykin, a frequent poster to the online discussion group, “I don’t feel that patients should pay for the privilege of getting a drug tested and out on the world market.”

But Gerald Campbell, PhD of Fairless Hills, Pa., noted: “Without being able to recover production costs, drug companies will never bother to test anything for a disease that doesn’t affect many people, or is heterogeneous and therefore requires lots of testing (like CFIDS). Costs of clinical trials can exceed $250 million. The HemispheRxes of the world don’t have that kind of cash.”

Presently, Ampligen costs $150 per 400mg dose. Early in the trial, patients will receive biweekly doses of less than 400mg. The dose is adjusted based on the patient’s responsiveness, weight and other factors.

HemispheRx is charging about $2,100 for the first eight weeks of the trial and about $2,400 per eight weeks for the remainder. That’s a total of $6,900 per patient for the 24-week trial, not including a doctor’s fees for administering the drug, which is done through intravenous infusion. For this trial, HemispheRx is requiring payment for the drug in advance.

There is some good news for those who’ve been in a prior Ampligen trial: a price break. If you were in an open label trial, you pay 70% if you were in a controlled study, you pay 50%. Also, for both this 20-patient program and the planned 100-patient program, HemispheRx promised The CFIDS Association of America Executive Director Kim Kenney at a May 21 meeting that the drug will be given free to between 5% and 8% of patients who meet the federal standards for “indigent.” Physicians and HemipheRx will decide who those patients will be, she reported.

The reason for the high cost, said Carter, is that manufacturing Ampligen is expensive and few patients are taking it right now. Third-party projections estimate that the drug will cost about $8,500 per patient by the year 2000 if the FDA approves it in 1998.

Three begin using drug

At press time, three patients already were taking the drug on an individual basis. Jonna Lannert of Culver City, Calif., is getting the drug at no cost, while Diane Evans of New Britain, Pa., and Naomi Weinstein of New York City are the fist U.S. patients to pay for Ampligen in a CFIDS clinical trial. Each won permission to receive the drug after their legislators and CFIDS activists pressured the FDA and the company to get them access to the drug because theirs were life-threatening situations.

CFIDS patients and activists Sara Oliver Millner and Danya Zucker facilitated the approval for 51-year-old Jonna Lannert, mobilizing elected officials, patient advocacy groups and health care providers. She began treatment March 6. Olsten Kimberly QualityCare, a home healthcare company, made at-home infusion available at no cost.

“I’m feeling stronger except for the pain, but I’m still bedridden,” she said in a telephone interview about 15 weeks into treatment. “People have noticed a definite change for the better in me; I seem more alive, more alert to them. I’m hopeful I’ll continue to improve.

Diane Evans, 28 began making the hour-long drive for her Ampligen treatment at Dr. Joseph Bellesorte’s Springfield, Pa., office the week of May 26. After the first few infusiosn, she admitted to feeling “a little bit worse than usual,” with intensified headaches and more joint pain.

“But it’s way too soon” to tell if Ampligen is making a positive difference in her health, she said, “I’m very hopeful.”

Naomi Weinstein, a 57-year-old former scientist, has been bedridden for the last 14 years. Severe keeps her lying flat on her back in a darkened room. She has developed diabetes and cardiovascular problems and requires around-the-clock nursing care.

“I’ve been fighting for this medication since 1990,” she said. “And every day that I lie here immobilized, my life is at great risk.” She is being treated by Dr. Maurice Beer in Manhattan.

Desperate patients

Despite the cost or effort involved, many CFIDS patients are willing, even eager, to sacrifice whatever necessary to take a drug that may help them.

“I know I would get a second mortgage for this treatment, because I’m pretty desperate,” said Adrienne Jensen, a 49-year-old from Chicago, Ill., who has spent the last 11 years battling the disease.

Philadelphian Gregg Davis agreed. “I’m desperate enough for an all-or-nothing approach. I would rather be dead than wait another 10 years in y condition for another miracle drug to pass FDA standards. Ampligen is my biggest hope of regaining what I once had.”

Others, skeptical of a drug the FDA has not yet approved, advise waiting. “Let’s face it, with a drug like Ampligen, which is so expensive it could generate unbelievable profits, there is every reason to be cautious about interpreting the results of preliminary studies,” said Eric J. Andersen of Ankeny, Iowa, a CFIDS patient who posts regularly to “There’s too much economic incentive for results to be skewed, for the researchers to minimize the side effects.”

Yet other CFIDS patients point out the value in any potential improvement in their day-to-day abilities.

“For those whose quality of life is very undermined by an illness, while you don’t necessarily want to be foolhardy, you are more willing to take risks with treatments if there is some reasonable hope of substantial improvement, relief or recovery,” said Judith Wisdom of Philadelphia, a sociologist who is currently unable to work. “That is, the most ideal and healthy treatment, if it ain’t out there, is not an alternative. Time passes. Life chances shrink. We don’t have nine lives. Under such conditions, some of us are willing to take informed chances.”

CFIDS patient Gerald Campbell believes the FDA should be limited to determining the safety of prospective drugs.

“Allowing them to determine efficacy also delays introduction of helpful drugs, screens out the whole population and adds dramatically to costs,” he said. “I believe the medical community should be the ones to determine efficacy, conditions for which the drug is useful and treatment regimens.”

Debating the merits

Charles Lapp, MD, a medical advisor to The CFIDS Association of America and a member of the Clinical Affairs Committee of the American Asociaiton for Chronic Fatigue syndrome (AACFS), believes the drug is safe and effective.

“Over 130 patients with CFIDS have been treated with Ampligen. Over 40,000 doses of the drug have been given worldwide (including in HIV and cancer studies),” he said. “Fifty percent of the (CFIDS) patients have recovered, have gone from bedridden back to work. Eighty percent have improved globally. It’s a drug that works marvelously.”

Daniel Petersen, MD, agreed, saying he considers Ampligen to be “at least 70% effective in highly selective patients.”

But others question that. “The studies on Ampligen are very controversial,” said Paul Levine, MD, in an April 15 Prodigy conversation. Levine, who specializes in neurological diseases and epidemiology, is former president of the AACFS and an editorial board member for the Journal of Chronic Fatigue Syndrome. “I know of only one published study [and] that has not been confirmed, and I think it’s still an unproven medication for chronic fatigue syndrome.”

Others raise concerns about HemispheRx’s use of publicity and public relations to promote the firm and its drugs.

“Although I would love to learn that Ampligen is the magic bullet for us, much of what I’ve read from the drug manufacturer sounds like hype,” said Ray Colliton, a support group leader from Pennsylvania. “The thing that concerns me the most is that the manufacturer claims that Ampligen will cure a very high percentage of the most severely ill CFIDS patients. The patients in Belgium may have been preselected to include only those within a subset of CFIDS patients likely to benefit from Ampligen. I’m convinced CFIDS is too complicated a problem for a single magic bullet.”

“No one seems to trust the company and its principals,” agreed Susan Fein, a 42-year-old CFIDS patient from Miller Place, N.Y., who’s been disabled since 1991. “The product may have merit, but they’ve been light on scientific publication all along.”

Susan McDermattroe, a CFIDS patient and HemispheRx stockholder, offers another perspective. “When you consider how much we spend now on drugs that don’t’ work at all – and how many times a year we visit the doctors for pain and pills, not to mention herbs, vitamins and therapies that don’t work at all – I think its’ worth a shot. Considering there is no drug designed for use in CFIDS, I’d say we have a good opportunity for at least a partial recovery. And when you think about it, it will work out the same monetarily,” she said.

CFIDS patient Jon Barnes agrees. “I would take it in a heartbeat if it were available in the U.S. I’d gladly give up some years of this miserable existence to have a few good years with Ampligen. The real question to ask yourself her is: Would you rather have a little more money in the bank and a miserable life or less money but be back to your old self? I vote for my old self. And so what if I have to take it for the rest of my life?”

McDermattroe predicted that Ampligen will soon become the drug of choice within the CFIDS community “if the insurance companies will pick up the tab.”

But Fein expected that won’t happen without a fight. “The same insurance companies who don’t want people diagnosed with Lyme disease because it often requires lengthy IV treatment will be fighting Ampligen tooth and nail. Or they’ll start fighting the diagnosis of CFIDS, requiring an objective test.”

Measuring clinical outcomes

One difficulty in Ampligen trials has been measuring the results, without a marker or a laboratory test that measures how sick a patient is. Karnofsky performance scores, used in past and current CFIDS trials to gauge improvement, are subjective; the patient may tell the doctor he’s feeling better but the physician has no way to verify improvement. Carter and an FDA medical officer said they are exploring ways to more accurately measure the effect of Ampligen in CFIDS patients. In this 20-patient trial, Carter said he “expects to track data similar to data previously reported and published,” which would include patient cognition, memory improvement, physical performance, quality of life and potential adverse reactions.

Eventually, Carter believes there will be a diagnostic test that makes CFIDS easier to diagnose, alogn with better ways to measure Ampligen’s effectiveness. “We’re hopeful that markers will be helpful, because they do give scientific insights,” said Carter. In addition to developing its own diagnostic technology called Diagen, Carter said “the company has supplied grants and aids to Dr. Robert Suhadolnik’s research and we envision that his work will allow tracking.”

“There’s no doubt that in the next year or two you’re going to see an increasing recognition of the incidence of this disease as physicians and patients become aware that there are tests that can be used to help identify and find this particular disorder,” he said.

Current trials

The Belgian Ampligen study, which began in May 1993, is ongoing. Lead investigator Kenneth DeMeirleir of the University of Brussels has reported an “80 % recovery rate.” Dr. DeMeirleir said the typical patient in the trial had been bedridden for between three and seven years prior to beginning the six-month treatment program. However, at least one woman who participated in that trial has posted messages to saying she relapsed a few months after stopping treatment.

On May 3, 1996, Canada’s health Protection Board made Ampligen available to CFIDS patients there. Carter said presently only one physician in Canada is prescribing Ampligen.

Dr. Guy Dore in Montreal said he’s treating a man from New York at a cost of approximately $12,000 (Canadian) for six months. He hopes eventually to treat as many as 40 CFIDS patients. “I’m very excited that it’s finally possible to use this drug, and I hope it does something for these patients.”

Carter said interest in the U.S. is high. “We’ve had a large outpouring on interest by prominent researchers from all parts of the country to participate in our most recent treatment protocol.”

Sites for trial

The 511 trial will be hosted by experienced CFIDS physicians or researchers. The company announced in lat June that five doctors had received approvals to participate. They are Dr. Charles Lapp of North Carolina, Dr. Daniel Peterson of Nevada, Dr. Joseph Bellesorte in Pennsylvania, Dr. Marsha Wallace in Washington, D.C., and Dr. Maurice Beer in New York. Another half-dozen doctors are in the approval process and more have expressed interest.

For physicians, such trials require time and attention. Dr. Peterson termed this trial “very difficult,” with requirements for tracking patient data, complying with FDA and HemispheRx regulations and swallowing the costs of clerical work.

While some doubt the long-term benefits of Ampligen once the treatment is completed, Carter said he believes will prove to be long-lasting.

“If you would take all the available clinical information, you would predict that 25-40% would require longer treatment – one or more years – whereas 50-60% would have a significant clinical benefit – a return to what they or their physicians deem a normal lifestyle – in six to nine months,” said Carter. “We certainly know that there are patients who require much longer therapy; Dr. DeMierlier and the clinical investigators in the U.S. have seen patients who, while they demonstrate clinical benefit in the first six to eight months, they nonetheless had not undergone a complete clinical recovery.

“The earlier placebo-controlled study does not suggest that any significant percentage of patients got worse,” said Carter. “The duration of benefits is always a challenging issue to address. In the U.S. as many as 17% of residents leave their state every year, and it’s harder to follow patients after a trial.”

But Ward Karns of Freemont, Calif., a participant in the 502A trial that began at the end of 1990, said: “No one ever tried to follow up with me, and I don’t know anyone else from the early trials who was contacted, either. I got even sicker than I had been within weeks of stopping Ampligen. Everyone relapsed to some extent.”

Some former Ampligen patients are so bitter about their experiences they have absolutely nothing positive to say about the drug or company that makes it. Their experiences in the trials, as well as the various difficulties HemispheRx has suffered over the years, were detailed in an article that appeared in the October 1994 issue of Philadelphia Magazine by writer Mindy Kitei.

Eager for action

Still, patients and CFIDS practitioners are anxious for the approval process to move forward.

“I have waited almost a decade for a drug, any drug that would provide a reasonable response rate to the hundred of miserable PWCs that I manage,” said Dr. Lapp. “This is a drug, the only currently available drug that offers the opportunity to improve or recover. I have seen it work miracles and I am truly thankful that I will have the opportunity to treat my patients with Ampligen.”

Patients, however are sick of waiting.

“I’m just really sick of reading about Ampligen and would like to know once and for all whether to look forward to it or not,” complained Mike Allen of San Francisco. In a posting on, he called Ampligen’s bump road through the approval process “the great pharmatease.” Carter assured those waiting that approval will very definitely come.

“My determination to helping PWCs is as strong as it has ever been,” said Carter. “This disease has been a mystery and a challenge to me as a scientist and as a physician. I have been determined to find a treatment from the beginning because of my personal acquaintance with PWCs. Over the years, watching their suffering has made me more determined to overcome obstacles and bring a therapy to market.”

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