My letter to Dr. Woodcock from earlier this week:
Jeannette K. Burmeister
[city, state, zip code] [city, state, zip code]
December 11, 2013
Via U.S. Mail & Email ([email])
Dr. Janet Woodcock
Food and Drug Administration
Director, Center for Drug Evaluation and Research
[city, state, zip code]
Re: Unequal Treatment of Ampligen and Bexsero
Dear Dr. Woodcock,
I am writing to you on behalf of myself and the vast number of patients who suffer from myalgic encephalomyelitis/chronic fatigue syndrome (“ME/CFS”), a disease classified by the FDA in the category of serious or life threatening. The arbitrary application by the FDA of the rules relating to drug approval seems to give more weight to the front-page news than the actual gravity of a disease. I am confounded at the FDA’s decision to approve the use of Bexsero at Princeton University to prevent further cases of meningococcus B causing meningitis while at the same time failing to provide Ampligen for ME/CFS patients earlier this year.
As an attorney who practiced at the world’s largest law firm, I am familiar with the application of laws and regulations, as well as the use of fair and responsible judgment. Unfortunately, I was forced to leave my position when I got sick with this mercilessly debilitating and unrelenting disease, ME/CFS.
The FDA’s decision to allow the import of Bexsero into the United States for the use in a vaccination campaign for approximately eight thousand students at Princeton University in an effort to prevent potential mass deaths, or other tragic cases, like serious complications such as the amputations in the case of one UCSB student, from meningitis implies one of two things. Either the FDA is concerned for the health and welfare of patients in the face of a serious and potentially life-threatening disease or the FDA applies the law in an egregiously unequal and arbitrary manner when it comes to severely ill patient populations. My question to you, Dr. Woodcock, is why the FDA did not apply same concern and medical judgment it is demonstrating for the Princeton cohort to its decision about Ampligen.
Ampligen was denied approval by the FDA in February of this year, even though the FDA’s advisory committee voted in December of last year that the drug was safe. The committee split its vote on the question of efficacy, in all likelihood due to a lack of understanding by the agency of the severity of the disease and the significance of clinical improvements for patients receiving the drug as part of clinical trials. In fact, Dr. Theresa Michele, FDA clinical team leader for the Ampligen decision, admitted and stressed, at the April FDA Drug Development Meeting, that she had not previously been aware of the symptoms of ME/CFS as clearly as she was as a result of listening to patients’ testimony at the April meeting. I cannot help but wonder if the decision not to approve Ampligen might have differed had there been a clearer understanding of the seriousness of the disease by the FDA before the decision was made.
There is no doubt in the mind of the majority of those fortunate ME/CFS patients who have had the benefit of Ampligen as trial participants that the drug is efficacious. Improvement in exercise capacity and recovery times as well as in immune-system markers show the efficacy of the drug objectively.
To give the unequal treatment of meningococcus B-caused meningitis and ME/CFS some perspective, to date, eight Princeton students have contracted meningitis. There have been no deaths and yet all affected students will have access to treatment. On the other hand, about one million patients have been severely ill with ME/CFS—with 25% of them living at the brink of death—not for weeks, but decades. Only very few of patients who live near one of a handful of clinical-trial sites—or move to one while leaving their families behind—and who can afford Ampligen (and in most cases also the added living expenses) have access to the drug.
In weighing the benefits and risks of receiving Ampligen—a drug ruled safe by the FDA—ME/CFS patients without access to Ampligen have no hope for improvement, unlike the eight Princeton students hospitalized with meningitis. In fact, ME/CFS patients have received a life sentence of daily suffering and frequent severe crashes (worsening of the multitude of their debilitating symptoms) after only minimal physical or mental activity, such as performing tasks of daily living like showering or grocery shopping. Patients can also count on multiple hospitalizations and shortened life spans.
The Princeton students have now the option of receiving the Bexsero vaccine. ME/CFS patients have been given no such option even though Ampligen, a safe and effective drug, is readily available.
I am one of the lucky few who are able to receive Ampligen twice a week. As a result, I now function at a much higher level than before I started Ampligen treatment, at the expense of having to live at an approved Ampligen infusion site, more than two hundred miles apart from my three-year old little girl and my husband. I only get to visit my family about every two to three weeks for three days. The fact that my husband and I are wiling to make such tremendous personal and financial sacrifices shows clearly that the benefit of Ampligen to my health and the quality of life for my family outweighs the cost in our lives, despite the heart-wrenching separation.
The FDA has the regulatory authority to approve treatments for ME/CFS, such as Ampligen, using less-stringent-than-normal rules, such as fast track, accelerated approval and priority review. The requirements for these avenues are met in the case of Ampligen. ME/CFS is a serious or life-threatening disease with an unmet need, as no approved treatments exists. Improvements in exercise capacity and recovery times as well as improvements in immune-system markers are appropriate surrogate end points.
Moreover, the FDA also has significant discretion at its disposal in determining whether applications have met the bar of “substantial evidence of effectiveness” of a drug (21 CFR §314.126(c)). The regulations in 21 CFR §314.105(c) state that the “FDA is required to exercise its scientific judgment to determine the kind and quantity of data and information an applicant is required to provide for a particular drug to meet the statutory standards.”
Regulations in 21 CFR §312.80 reinforce the need for flexibility in the case of life-threatening and severely-disabling illnesses by addressing “procedures designed to expedite the development, evaluation, and marketing of new therapies intended to treat persons with [such] illnesses, especially where no satisfactory alternative therapy exists,” as is the case with ME/CFS. The regulations state that the “FDA has determined that it is appropriate to exercise the broadest flexibility in applying the statutory standards, while preserving appropriate guarantees for safety and effectiveness. These procedures reflect the recognition that physicians and patients are generally willing to accept greater risks or side effects from products that treat life-threatening and severely-debilitating illnesses, than they would accept from products that treat less serious illnesses. These procedures also reflect the recognition that the benefits of the drug need to be evaluated in light of the severity of the disease being treated.”
Furthermore, the FDA has the ability to waive any or all of the criteria outlined as required for “adequate and well-controlled studies.” The regulations in 21 CFR §314.126(c) state, “The Director of the Center for Drug Evaluation and Research may, on the Director’s own initiative or on the petition of an interested person, waive in whole or in part any of the criteria [for adequate and well-controlled studies] with respect to specific clinical investigation, either prior to the investigation or in the evaluation of a completed study.”
I implore you and the FDA to take the long overdue step of approving Ampligen for the treatment of ME/CFS—if necessary by expediting the approval process and keeping in mind that ME/CFS is in the category of life threatening or severely debilitating diseases and lacks any alternative treatments—and, thereby, finally improving the lives of hundreds of thousands of patients and their families and giving them some hope.
Attorney at Law, California and Germany
Margaret Hamburg, Commissioner of the Food and Drug Administration ([email])
Joseph Pitts, U.S. House of Representatives ([email])