The Fate and Fortunes of the Lazarus Drug, Part Two
Farewell Ampligen...Praise be, FDA
And Then There Were None….
In a year of new chapters beginning, one chapter in the tumultuous 30-plus-year history of modern ME has quietly ended. Hemispherx, the manufacturer of Ampligen, a drug that has shown enormous promise in treating ME since the late 1980s, is “repurposing” its premier drug to treat other diseases in other countries, including Western Europe, Turkey and South America. For more than a year, Hemispherx’s leadership has been making arrangements to investigate Ampligen’s ability to treat lethal cancers like the fast-rising pancreatic cancer, as well as deadly infectious diseases such as Ebola that emanate from Africa and Asia but threaten the world.
The company is reluctantly, according to its top executive, CEO and president Tom Equels, rapidly winding down its efforts in ME in the United States.
“There are probably fewer than ten (M.E.) patients on Ampligen in the U.S. today,” Equels says, a comment borne out by interviews with doctors in the U.S. licensed to administer Ampligen in recent decades.
Charles Lapp, MD, an ME specialist who has offered Ampligen to sufferers in Charlotte, NC for years said during an interview last summer, “Until a few months ago, we had about six patients on Ampligen. Numbers have fallen off considerably in the last three months because of production and supply problems.”
Lapp said he had been able to continue to supply the drug to a few patients only because his infusion nurse had been hyper-vigilant about “keeping up inventory.”
In New York City, ME specialist Derek Enlander provided the drug to two patients until spring 2015. Although near New Brunswick, NJ, where the drug is manufactured, Enlander ended the program abruptly when he ran out of the drug. Both patients regressed.
Incline Village, NV has been for many years an Ampligen infusion site, based at Sierra Internal Medicine, Dan Peterson’s clinic. “They have had droughts,” Lapp said of the Nevada site. At the start of last summer, there were perhaps 19 patients receiving Ampligen there, he speculated. Lapp suspects patients “got discouraged and quit or went on drug holidays.”
The Charlotte doctor added, “Hemispherx is no longer allowing patients to return to the program after extended drug holidays.”
At one time, ME clinicians were infusing Ampligen into patients in Nevada, North Carolina, New Jersey, Florida, New York and Utah. Approximately 1,000 ME sufferers have received Ampligen since the first patient, the seizure-ridden, bedbound Nancy Kaiser, whose doctor Dan Peterson considered her to be near death, received Ampligen in Nevada in 1988. Though Kaiser ultimately died in 2008 she was restored for years by Ampligen. The drug enabled her to return to her life-long passions, golf and swimming. She also experienced a 40 point rise in I.Q.
In the decades that followed, nevertheless, the universe of ME patients who were lucky enough to gain access to Ampligen remained infinitesimal. Many were upper middle class or just plain rich, able to pay for both “cost recovery” of the drug itself and infusion costs. Others sold their houses or drew down their retirement funds.
If two million Americans have the disease, then just .05 percent of all patients have had the opportunity to be treated with Ampligen. If—conservatively—one million Americans have ME, then 0.1 percent of the universe of ME sufferers have had access to Ampligen. Some readers of this column may have more Twitter followers.
A price increase, Lapp suggests, is the primary reason use of the drug has dwindled. Hemispherx’s protocol has been 400 milligrams twice a week, dispensed from two 200 milligram glass bottles via IV infusion. Some doctors experimented with the dose, dropping it to one bottle two times a week. Given the high costs of manufacturing Ampligen, Hemispherx, appointed an independent auditor last year to determine a fair market price for the drug. After the audit last summer, Hemispherx raised the price of a bottle of Ampligen from $75 to $200, the cost to Hemispherx of manufacturing Ampligen.
“Treatment requires 400 milligrams at a cost of $400 twice weekly, or $800,” Lapp points out. “That’s $3,200 per month, or $38,400 per year.”
Nevertheless, he adds, “Last I heard—that’s less than one dose of Rituxan at Stanford.”
Rituxan, a lymphoma drug that destroys the body’s B-cell population where most lymphoma resides, has had mixed results in ME trials conducted by Norwegian oncologists. Multiple doses may be required to sustain remission. The results of another Rituxan trial are expected soon.
In general, Lapp continues, “It’s the cost of the drug, the lack of insurance reimbursement and Hemispherx’s requirement to have an IV infusion twice weekly such that one really has to live very close to the infusion center. Therefore, a patient has to be able to emigrate either to Charlotte or Lake Tahoe for at least twelve months, probably much longer. Not many people, especially those with families, are able to do that.”
In short, Ampligen, a drug with an estimated 50 percent efficacy rate and an excellent safety profile after approximately 100,000 administered doses, has remained out of reach to all but the most fortunate (and desperate) ME sufferers in the United States since it showed success as a therapeutic agent for ME 29 years ago. Today the drug is virtually unavailable to all.
In spite of these harsh realities, Lapp expressed confidence in the company’s continued commitment to ME.
“Hemispherx is clearly seeking other profit centers,” Lapp told me recently. “But that doesn’t mean they will give up on CFS-ME. The board members have been closely involved with CFS-ME for decades.”
Lapp added, “The company has been seeking unique ways to finance one more phase three study. Maybe that will work out.”
New Leadership, New Horizons
Nothing happens in a vacuum, of course. A year ago, the board of Hemispherx took the unusual step of firing Ampligen’s inventor and the company’s CEO and founder, the often brazen and by some accounts eccentric William Carter. In the late 1980s, Carter made the decision to commit Hemispherx’s scientific and manufacturing efforts to ME. In 1991, he presented the impressive results of an ME trial to a group of infectious disease specialists meeting in Chicago. The NIH’s Stephen Straus stood to express his incredulity, silencing further discourse at that particular meeting. Carter seemed unfazed, as if he were used to bullies. Straus’ antagonism, in retrospect, was an ominous foreshadowing of the drug’s fate. At the time no one at Hemispherx dreamed the company’s struggle to persuade FDA to approve Ampligen would take thirty years and—at least for now—end in failure. (Straus, whose negative influence over the disease persists yet today, was the FDA’s advisor on ME until his death in 2007.)
Carter believed that in the case of a serious disease for which there was such a profound unmet need for treatment, FDA would agree to fast track Ampligen. After all, the drug agency for some time had been approving AIDS drugs that demonstrated less efficacy in HIV disease than Ampligen demonstrated in ME. Carter also believed that the market for a successful ME drug was already enormous in early 1990s and that it was likely to grow rather than shrink.
Thus, he sought to fast track Ampligen based on outcomes from the company’s first double-blind trial of 92 patients in 1991. He stopped the trial when the patients on the drug began to diverge radically from patients receiving placebo. Patients and their doctors, too, recognized the difference, which had the unintended result of unblinding the trial. A few in the trial sued when the trial was prematurely halted. They were the self-styled “Ampligen Twelve” in Nevada. A local judge agreed and awarded them an extra year of Ampligen.
The episode was the first volley in an uneasy relationship existing between the tiny biopharma company and its targeted patient group for decades.
The skirmishes have continued as Hemispherx has struggled to push Ampligen over the finish line at FDA. Last year’s price hike resulted in patients lobbing accusations of corporate greed at Hemispherx. More recently, some advocates have turned their attention to the NIH, which has not undertaken a drug trial in ME since Stephen Straus performed his much-criticized Ayclovir trial in 1987.
Courtney Miller, a board member of the Simmaron Research Foundation in Incline Village, NV who is married to Ampligen recipient Robert Miller, started a petition to the NIH last spring. She asked that NIH conduct clinical trials with drug therapies in ME—starting with Ampligen. Bob Miller, one of those who sold his house to obtain the drug, has gone on a hunger strike and skydived from a plane in a personal expression of support for the approval of Ampligen by FDA. (http://www.meaction.net/2016/06/23/help-us-ask-nih-to-fund-an-ampligen-trial-today/)
Carter has retired to his house in the Florida Keys. The Keys have been the site of countless Hemipsherx annual stakeholder meetings over the years. If Ampligen is approved, Carter will share in the profits.
In Carter’s place, the board promoted the company’s president of five years, Tom Equels, a Vietnam war helicopter pilot who left that war with a bagful of medals for bravery and in time became a powerhouse attorney in South Florida.
“If the question is, are we abandoning ME, the answer is NO,” Equels says before he even hears the question. “But we have to come up with a business plan that assures the survival of the company and the approval of Ampligen for as many applications as possible as quickly as possible. That will assure the approval of Ampligen in some form for ME.”
Next: Tom Equels and the Science of Ampligen