The below article is Part Four of a series that began in the Winter 2015/2016 edition of the FARA Advocate.

"Drug Development Series: Drug Access and Supplements"

By Jane Larkindale, PhD

Patients with FA are, understandably, impatient for new treatments. Many say that they are willing to accept some degree of risk in taking a new treatment, if it has the potential to be beneficial for them. So, how can a patient get a potential treatment, when there is nothing on the market that has been approved for FA? Firstly, we need to bear in mind that if a treatment has not been approved for FA, it has not been fully tested in patients – there is a real risk that it will be ineffective, or worse still it could harm FA patients. However, if the patient is willing to risk that, there are several ways to try.

Supplements vs. Drugs: The most common unapproved treatment taken by FA patients is probably idebenone, which is available as a dietary supplement, but not currently as a drug. Idebenone was tested in clinical trials for FA, but failed to result in a statistically significant change in the outcome measure, and no further trials are underway. Patients have, however, continued to take forms of the drug that are available as a supplement. Dietary Supplements are governed by the FDA, just as drugs are, but the barriers to sales are much lower. The seller of a supplement does not have to prove to the FDA that it has an effect in any specific disease (and cannot claim that it does). In contrast, a drug developer has to prove through extensive tests that their drug is both safe and effective in specific diseases. The FDA stringently governs how a drug is manufactured, and exactly what is in the tablet – this is not the case with a supplement. Thus, supplements may be available on the market which a patient might think helps his or her disease, and he or she would be able to access it. However, there is no stringent proof of what is in that supplement, or that it has an effect. Further, if a drug form of that supplement is approved by the FDA (as Santhera hopes idebenone will be for other diseases), the owner of that drug can ask the FDA to step in to prevent sales of the supplement form, to protect patients with the disease indicated from taking a form of the drug that is either dangerous or ineffective. In the idebenone example, FA patients would then no longer be able to buy the supplement that they have previously been taking, once a drug form was on the market for another indication. 

Off Label Use: This refers to a doctor prescribing a drug for a condition for which it has not been approved. Any drug that your doctor prescribes you is likely off-label, as nothing has been approved to treat FA, although the drug will be approved for some other disease, most likely a similar condition in the non-FA population (e.g. cardiac drugs). In some cases, large amounts of data support the use of a drug that is only available off-label – such as steroids in Duchenne Muscular Dystrophy, where many trials have proven their effect. In this case, as the drug is available generically, there is no financial benefit to a company getting them approved specifically for this population, but it is good clinical practice to use them anyway, as data has repeated shown them to be effective. The difficulty in using drugs off label, particularly newer drugs that are very expensive, is that insurance companies (or Medicare/Medicaid) often will not cover their use, as they are not FDA-approved. This can make using the drug prohibitively expensive.

Expanded Access or Compassionate Use: These terms mean the same thing, and refer to FDA programs that can allow patients to get access to treatments that have not yet been approved. There are three kinds of applications for expanded access – applications for an individual patient, applications for an intermediate sized population or applications for widespread use. In all cases, the applicant (usually the treating physician in the case of an individual patient, or a company when multiple patients are involved) must justify the use. They need to show the urgent need of the patient(s) and justify the risk of using an unproven treatment. They must show that there is no alternative treatment for the patient. They must also demonstrate that by letting the patient(s) take the drug it will not interfere with ongoing clinical trials, and that the patient could not access the drug through a trial (e.g. if the patient is a late stage FA patient, and the only ongoing trials only include patients who can still walk). Finally, in order to get access to an experimental treatment, the patient’s physician has to take responsibility for monitoring the treatment and the company that manufactures the drug must agree to provide it – which is not always possible for small companies due to their stocks of drug and/or cost. As a consequence, and as there is often not enough data for an experimental drug to offer a good risk benefit ratio until it is near approval, compassionate use is not widely used in FA.

In recent years “Right to Try” bills have been introduced in multiple states, which would allow terminally ill patients to get access to experimental treatments. These bills have been signed into law in some areas. They essentially try to expand, and make simpler, compassionate use laws to make it easier for late stage patients to access experimental treatments. However, the fact remains that in FA, there are no treatments yet where there is significant proof of effect. However, with so many drugs in the pipeline now, we hope that will change in the next few years!

← Read Part Three: "Drug Approvals and What Happens Next"