Access to Potential Alzheimer's Treatments Outside of Clinical Trials

Summary:  The FDA’s “Expanded Access to Investigational Drugs for Treatment Use” rule provides a way for patients who can’t participate in clinical trials to gain access to potential treatments not yet approved by the FDA.  Despite optimistic headlines about Alzheimer’s cures and breakthroughs, many drugs currently in trial seem to have only incremental benefits.  This may keep demand for expanded access to potential Alzheimer’s treatments low.

Over the past few months, I’ve received several emails from people diagnosed with Alzheimer’s or their caregivers asking how they can get access to Alzheimer’s drugs still in clinical trials.  Most of these inquiries were about Dimebon, Rember or potential “Alzheimer’s vaccines” such as Bapineuzumab.

In each case, someone saw an optimistic media report about the promise of a drug in clinical trials (an “investigational drug”), and wanted access to it before trials were completed and it could be approved for the U.S. market. 

The easiest way to get access to these or other investigational drugs is to participate in clinical trials of the drugs, of course.  Even if you were to receive a placebo during the trial, there is often an opportunity to take the investigational drug for a period after the trial is over.  By participating in clinical trials, you also help build data about whether or not a treatment is effective.

But what if you can’t take part in a clinical trial?  There are a number of reasons the readers I’ve heard from aren’t eligible for the trial they’re interested in, including:

• there are no trial sites within easy driving distance
• a caregiver is required to participate [in some trials], and no one is available
• they suffer from illnesses other than Alzheimer’s that exclude them from the trial
• they are taking medicines for Alzheimer’s or other conditions that exclude them from the trial
• they do not fall within the age range specified for the trial
• a physical disability and/or transportation difficulties prevent them from making frequent visits to a trial site.

In the U.S., the Food and Drug Administration (FDA) has a rule [“Expanded Access to Investigational Drugs for Treatment Use”] in place to help people with serious or immediately life-threatening diseases get access to investigational drugs.  This rule is meant to help those who have no other treatment options and can’t participate in clinical trials.  At least theoretically, this rule would allow Alzheimer’s patients to gain access to Alzheimer’s drugs still in trial (more on this in a minute).

Recent Changes to the FDA’s Expanded Access Rule

To improve access to investigational drugs, the FDA recently clarified the Expanded Access rule and launched a new web site to improve access to investigational drugs.  Under the revised rule, expanded access is available to

• individual patients
• “intermediate size” groups of patients
• “large” groups of patients. 

For any of these categories, your doctor, the pharmaceutical company involved and the FDA must work together to make arrangements for you to receive an investigational drug.  There is no requirement for doctors or pharmaceutical companies to participate in this kind of program.

For each application to the FDA for expanded access, the following information is needed:

• why the investigational drug is better than existing treatments
• how the drug will be administered
• description of the facility where drug will be manufactured, and what controls are in place to ensure quality
• safety information
• procedures, tests and monitoring needed to minimize the risk of taking this drug.

Generally, the larger number of patients that are involved, the more additional requirements there are for approval.  For individual patient access, your doctor must say that the probable benefit of the drug is greater than the probable risk in your situation.  The manufacturer or pharmaceutical company involved must agree to provide the investigational drug (along with information about administration and safety), and either that company or your doctor must submit an application to the FDA.

For intermediate size groups (perhaps from 10 to 100 people), there must also be at least preliminary clinical evidence the drug is or might be effective, plus evidence the drug is safe at the dose and duration proposed for treatment. 

For large groups, there must be more evidence the drug is safe and effective (typically information from a completed phase 2 or phase 3 clinical trial), and the pharmaceutical company must be actively pursuing FDA approval for marketing the drug.

In all cases, the FDA must determine that expanded access won’t interfere with clinical trials necessary to test whether drug is effective. 

Expanded Access for Alzheimer’s Investigational Drugs?

So, what about expanded access for Alzheimer’s drugs currently in trial? 

Certainly Alzheimer’s is considered a serious disease or condition, and would qualify for the FDA’s expanded access program.  And for many of the patients who can’t participate in clinical trials, I think you could make the case that existing treatment options are not very effective. 

But if there are cases where pharmaceutical companies are providing expanded access to Alzheimer’s investigational drugs now, they are not well-publicized.  Companies providing expanded access are required to register those programs in the clinicaltrials.gov database, but there are none listed for Alzheimer’s. The requirement to register these programs is new, so database may not be complete. 

TauRx (Rember), Medivation (Dimebon) and Elan (Bapineuzumab) public relations personnel did not reply to my emails asking whether they currently offer expanded access or have any plans to.  William Thies, Chief Medical and Scientific Officer of the Alzheimer’s Association, says he’s not aware of any expanded access programs for Alzheimer’s drugs. 

     William H. Thies, Ph.D.

So why isn’t there widespread use of expanded access for Alzheimer’s investigational drugs?   One reason may be that there’s not a lot of evidence that the drugs currently in trial are very effective.

“In the Alzheimer’s world, there hasn’t been anything that looked revolutionary enough that there has been a great desire for expanded access to investigational drugs,” says Dr. Thies.  “The process is good to have in place, though.  When an extremely effective medicine is developed, we will advocate for expanded access.  But while we’re still talking about incremental benefits, you run the risk of dismantling the clinical trials process."

Another reason there’s not much use of expanded access for Alzheimer’s may be financial.  Manufacturing investigational drugs can be expensive, and under the FDA’s recently revised rule on charging for investigational drugs, pharmaceutical companies can charge patients for the direct costs of providing these drugs through expanded access programs.  For intermediate or large populations, they can also charge for the costs of safety monitoring and administration.  There’s no guarantee that Medicare, Medicaid or private health insurance will cover these costs.

If you and your doctor agree that you would benefit from expanded access to an investigational drug, and you don’t qualify for the clinical trial, check out the FDA’s new web site on expanded access.  If you need more information, you can contact the agency’s Office of Special Health Issues at OSHI@oc.fda.gov or 301-827-4460.

Comments

[kollagen]

I think there must also be at least preliminary clinical evidence the drug is or might be effective, plus evidence the drug is safe at the dose and duration proposed for treatment.