In this conversation with Gabrielle Strobel, the husband of a 39-year-old woman with early onset familial AD (eFAD) discusses the uncharted territory of clinical trials for eFAD patients. All names are pseudonyms. See our previous interview with this couple, A Diagnostic Odyssey.
ARF: Megan is in the care of a highly regarded neurologist, an academic physician-researcher. We can assume he does the best there is for her. A cholinesterase inhibitor, a statin, and a past phlebotomy (i.e., bloodletting) series to treat her hemochromatosis—is that basically the extent of her treatment?
ARF: Before we talk about drug trials—any changes to her treatment?
Brad: We recently started being evaluated by a physician who practices applied kinesiology. He has been able to help some with Megan's gait. We have changed her medications slightly based on his suggestions. We have been including Dr. Myers on any changes, to which he has agreed. It is too early to tell if it has affected progression of her EOAD.
ARF: How is Megan doing?
Brad: She has been relatively stable; however, there is still a decline in her gait and in her cognitive abilities.
ARF: Have you tried to find a clinical trial for her?
Brad: I am gathering information. I have sources at a contract research organization, and some physicians have sent me what they know. Our neurologist is asking around among people at companies. He talked with someone at Lilly about their γ-secretase inhibitor. I am at the point where I need to review the information I have received from everyone and get my experts together and decide on what to go after.
ARF: Have you gotten signs that Megan would be allowed to enter clinical trials given her young age?
Brad: That is a big worry. The trials I found have a starting age of 50+. I can partly understand that, but surely people know there is the early onset form of this disease. Why do they exclude those people? Will they make an exception or do they just flat-out ignore them?
ARF: Experimental medicines exist, but you'd have to blaze a trail to obtain some for your wife.
Brad: I know. I have many questions. Besides getting access to any study drug, another problem is that she cannot take something else for the duration of the trial, so if something more powerful comes along midway through a trial, what do we do? What drug to pursue is a difficult decision. I also worry that I do not want to waste 6 months having her on a placebo. I need an active study drug for her. Do I try to negotiate an exception so she can join a trial, or do I try instead to obtain a drug outside of a trial and have her doctor treat her with it? What has a better chance of saving her?
ARF: Scientists agree that ultimately there will probably be combination therapy for AD, with different drugs addressing different aspects of AD—anti-amyloid, neuroprotective, antioxidant, anti-inflammatory, cholinergic, hormonal, metabolic. But at this point, each candidate drug is being tested individually. Trial patients receive standard therapy besides study drug, but rarely two different study drugs. Has the concept of Compassionate Use come up in your discussions?
Brad: I am aware of it from HIV and cancer but not in AD. It really should be discussed. This hit us in the prime of life. I recently contacted the FDA to understand the Compassionate Use route. I found out that there is another route to possibly take that is not under a formal single patient IND. The FDA will allow a patient to receive, via mail, an experimental medicine if it is prescribed and given under the care of a physician. They prefer if it is a compound that currently has an IND filed with the FDA. However, a patient will still need to work with the company to get access to the drug.
ARF: What kinds of potential or experimental drugs have you explored?
Brad: Our neurologist has considered some issues related to the balance of metals. We recently tried a treatment regimen around this theory, but did not notice an improvement. We are also looking at some other drugs that may be available but not currently prescribed for Alzheimer's.
ARF: Have you and Dr. Myers decided on which ones would hold some promise for Megan?
Brad: We frequently discuss current drugs and approaches. I try to stay up-to-date on current research, and he is great at listening to the research findings I come across. We are currently exploring an experimental drug and have been in contact with the company who is developing the drug.
ARF: What exactly did you do?
Brad: We contacted members of the Scientific Advisory Board and the CEO of the company by phone and e-mail. The company is currently considering our request for Compassionate Use. Dr. Myers has also been in contact with another company about some of their products, but they were not open to Compassionate Use at this point. He also contacted yet other companies.
ARF: What response did you/he get?
Brad: Each of the people has been sympathetic to our situation, and one of the SAB members has offered some of his research to Dr. Myers.
ARF: Did all sponsors you contacted react in the same way?
Brad: All have been sympathetic, but there have been mixed results in their openness to Compassionate Use.
ARF: Where your requests were rejected, what reasons did the sponsors give?
Brad: One of the denials was due to some previous clinical setbacks with that company's treatment approach. We have not followed up at this point to see if their view has changed, but we may contact them in the future to reconsider our request if their current treatment appears to do well in the clinic.
ARF: What about the risk of serious side effects with a barely tested drug?
Brad: It's a risk-benefit analysis. Right now, we know that our family member will likely pass away in 5-7 years, and that half of that time will likely be in a somewhat vegetative state. I personally think EOAD patients would be very willing to sign up for a trial even though the toxic effects of the treatment were unknown, or even given some known side effects of the treatment, if it offered a reasonable chance to improve cognition and AD symptoms for some time.
ARF: What would you suggest?
Brad: Couldn't the drug be made available for EOAD patients in a small, open-label observational trial that would allow good access to the active drug? The EOAD patients have a lot of energy, and the caregivers tend to be more observant of changes in their loved ones as they have so much going on and small changes are noticed more (at least that's my opinion). It is dreadful to watch our loved ones waste away without being able to help when we know that there are many drugs being studied for treatment of Alzheimer's. It seems to me like the FDA would allow companies to be more lenient by allowing them to separate the results of any EOAD trials if the main concern is not to disrupt the approval in LOAD patients.
ARF: So where do things stand in June 2007?
Brad: We don't have access to experimental therapy for Megan yet. We are considering further ones, and are working on obtaining access through off-label use and/or other approaches.