FDA Set to Review Ampligen Application

Today there is no FDA-approved treatment for CFS. The first drug to be considered for this designation is now under review by the Food and Drug Administration (FDA) after more than two decades of study. Rintatolimod (trade name Ampligen), is an immunomodulatory drug administered by I.V. infusion. There have been several blinded and open studies of Ampligen in CFS since the late 1980s. In August, the manufacturer, Hemispherx Biopharma, submitted its completed New Drug Application triggering a final review as the last step before FDA decides whether the drug can be marketed to the public. The company has to undergo several onsite evaluations to ensure the drug can be manufactured safely and reliably and an advisory committee will meet later this month to review data compiled by the company by which it aims to demonstrate the drug’s safe and effective use in CFS.

The Dec. 20 meeting of the Arthritis Advisory Committee (which also reviews products for lupus and other non-arthritic conditions) will be a first for CFS. The advisory committee roster will be posted by FDA by Dec. 18, 2012, along with other materials about the drug application and questions the advisory committee will be asked to vote on at the meeting. The advisory committee is expected to include some professionals with CFS expertise and it is customary for one patient representative to be seated on the committee.

The long and somewhat controversial history of the drug and the manufacturer has contributed to strong feelings about this topic. People with CFS who have been significant responders to the drug are expected to attend and press for approval and expanded access. There are others who remain concerned about the relatively modest benefit published data shows, the company’s failure to conduct a larger blinded study as requested by FDA in 2009, and the potential high cost (considering the drug cost, twice weekly infusions and monitoring tests). The Association’s scientific director, Dr. Suzanne Vernon, and I will attend the Dec. 20 meeting. I have been given three minutes to speak to the need for effective treatment during the session dedicated to hearing public comments. The Association has no role in the decision-making process about whether to approve or decline the request from Hemispherx to market the drug.

The FDA has invited patients and other stakeholders to submit written testimony about their experience that might be relevant to the decision about whether to approve Ampligen for wider use. Testimony can be short (just a few sentences) or long. Here are some factors that FDA and the advisory committee will consider in its decision that people living with CFS are uniquely qualified to provide input about:

  • Severity of the condition
  • Which symptoms of a condition patients most desire to be alleviated or reduced
  • What side effects of a medication patients are willing (or unwilling) to tolerate
  • Availability of other treatments
  • Acceptable risks and benefits of available or new treatments (see additional information below)

Written comments should be submitted to AAC@fda.hhs.gov by Dec. 6, 2012. [Note: Comments can be submitted after Dec. 6, 2012 to ME-CFS-Meeting@fda.hhs.gov, although they will not be considered by the Arthritis Advisory Committee. They can help FDA to understand ME and CFS more fully when other regulatory decisions are made.]

The Arthritis Advisory Committee will vote whether to recommend approval at the end of the Dec. 20 session, although FDA is not bound by the committee’s guidance. Under fast-track provisions for serious conditions, a decision about marketing approval is targeted to be made by Feb. 2, 2013. In 2011 the FDA approved about 30 applications to market novel drugs. Approvals are customarily subject to further post-marketing studies, tight surveillance for adverse events and broad education programs to inform providers and patients about the safe use and relative risks and benefits of new products.

So far the impending decision about Ampligen has received more attention from financial media outlets than medical press. Hemispherx Biopharma is a publicly traded company, so there is much speculation about financial rewards should Ampligen be one of the first novel treatments approved in the new year. Here are a few of the recent media articles that make both positive and negative predictions for the outcome:

Additional Comments on Risk/Benefit:

Assessing relative risk and benefit is a calculation each of us performs daily in many different aspects of our lives. The FDA must weigh the apparent risks and benefits for every therapy it considers and must continue to evaluate those risks and benefits even after treatments and devices are placed on the market. While medical professionals and researchers can contribute valuable data to inform that assessment, patients are the ultimate voice in the equation. There is a higher tolerance for risk for therapies that extend life or improve quality of life for serious conditions compared to symptomatic relief for minor health conditions.

It’s ultimately a very personal decision about how much risk to accept as a trade-off for potential benefit. Think about the equation like driving a car. Some people try to maximize safety when they drive. They purchase cars with highly rated safety features that offer added protection in the event of an accident. Others look for high performance and speed in a vehicle. But either type of car can be driven with safety or speed in mind and every driver is subject to risks like road conditions and other drivers on the road that affect the safety of any particular outing. In deciding on therapies, some patients wait until several well-controlled studies have shown the drug to be safe and effective. Others are willing to try something with less evidence or only suggested theoretical benefit in hopes of finding relief. Individuals who participate in clinical trials often do so with uncertain benefit or risk to themselves in order to advance research and potential new therapy development.

At the risk of oversimplifying, FDA’s regulatory role in approving new medicines is like setting safety standards for cars and traffic rules to guide safe driving. How much risk you’re willing to tolerate in a new therapy is usually expressed in terms of how many chances in 100 you’d be willing to accept of a) death or b) serious side effects in exchange for what benefit. For example, “I’d be willing to accept 1 chance in 100 of death and 10 chances in 100 of serious side effects if the new treatment offered 50% improvement in my daily function.” Even the safest drug can be used in unsafe ways and some toxic treatments can be life-saving in certain circumstances.

Overall, the FDA has to determine that a drug is both safe (does not pose undue harm for inadequate benefit) and effective (it provides the chance of meaningful improvement for a given symptom or condition) before it will allow the drug to be marketed. As stated above, that calculation is continuously assessed even after approval with what are called “post-marketing” studies and surveillance efforts. You can help the FDA understand the risk/benefit tolerance in the CFS community by sending a brief (or long) statement to FDA by Dec. 6: AAC@fda.hhs.gov  [Note: Comments can be submitted after Dec. 6, 2012 to ME-CFS-Meeting@fda.hhs.gov, although they will not be considered by the Arthritis Advisory Committee. They can help FDA to understand ME and CFS more fully when other regulatory decisions are made.]

The FDA Arthritis Advisory Committee meeeting on Dec. 20 will be webcast live. More details about the meeting and how to access the webcast can be found on the FDA’s site at http://www.fda.gov/AdvisoryCommittees/Calendar/ucm324972.htm.

K. Kimberly McCleary served as the Association’s chief staff executive from 1991-2013.

December 4, 2012