Personal Blog #11 ... Is Aducanumab an Effective Treatment for Early Stage Alzheimer's? ... 11/2/19

Of the top 10 causes of death in this country, Alzheimer’s disease (AD) is the only one with no effective means of prevention, treatment or cure. Any pharmaceutical or biotech company that discovers medication to effectively treat, let alone prevent or cure AD, will help millions of people … and make millions of dollars.  We often see reports of successful Phase I or Phase II clinical trials demonstrating positive effects of new experimental AD medications, but we have yet to see reports of effectiveness in a Phase III clinical trial.  The National Institutes of Health (NIH) describes the different phases of clinical trials as follows:  (Note: the NIH website may be accessed at … https://www.nia.nih.gov/health/what-are-clinical-trials-and-studies.)

"Clinical trials advance through four phases to test a treatment, find the appropriate dosage, and look for side effects. If, after the first three phases, researchers find a drug or other intervention to be safe and effective, the FDA approves it for clinical use and continues to monitor its effects.

Clinical trials of drugs are usually described based on their phase. The FDA typically requires Phase I, II, and III trials to be conducted to determine if the drug can be approved for use.

• A Phase I trial tests an experimental treatment on a small group of often healthy people (20 to 80) to judge its safety and side effects and to find the correct drug dosage.
• A Phase II trial uses more people (100 to 300). While the emphasis in Phase I is on safety, the emphasis in Phase II is on effectiveness. This phase aims to obtain preliminary data on whether the drug works in people who have a certain disease or condition. These trials also continue to study safety, including short-term side effects. This phase can last several years.
• A Phase III trial gathers more information about safety and effectiveness, studying different populations and different dosages, using the drug in combination with other drugs. The number of subjects usually ranges from several hundred to about 3,000 people. If the FDA agrees that the trial results are positive, it will approve the experimental drug or device.

A Phase IV trial for drugs or devices takes place after the FDA approves their use. A device or drug's effectiveness and safety are monitored in large, diverse populations. Sometimes, the side effects of a drug may not become clear until more people have taken it over a longer period of time.)"

Biogen, a major biotech company, ended its Phase III clinical trial with a new experimental medication, aducanumab, on March 21, 2019 because testing results indicated that it was ineffective.  So how is one to interpret Biogen’s announcement on October 22, 2019, that it will ask the FDA to approve aducanumab as a new treatment for early stages of AD? 

On their website, www.biogenalzheimers.com, Biogen states that after their study ended in March, “a new analysis of a larger dataset” showed that … “Patients who received aducanumab experienced significant benefits (my underlining) on measures of cognition and function such as memory, orientation, and language.  Patients also experienced benefits on activities of daily living including conducting personal finances, performing household chores such as cleaning, shopping, and doing laundry, and independently traveling out of the home.”  Biogen plans to submit their new data to the FDA in early 2020 to seek approval to market aducanumab.  

If the FDA determines that Biogen’s data support aducanumab as an effective treatment to slow the effects of AD, that would be a major step forward and offer tremendous hope to people with AD and their caregivers.  But before I get too excited, I want to see that results reported as “significant benefits” are what I refer to as “real world” benefits.  Reports of “statistically significant” results on paper/pencil tests measuring cognition, or of brain scans or biomarkers measuring a decrease in amyloid beta protein in the brain, are always welcome. 

However, such measures do not necessarily translate into more effective patient functioning at home or in a facility.  Answering 1 or 2 more questions correctly on a cognitive test or remembering 1 or 2 more words on a memory test may yield “statistically significant” results but may not always mean more effective functioning in the real world.  However, medication resulting in significant improvement for people with AD for 6-12 months or longer as they deal with activities of daily living or who can continue to go shopping or travel independently outside the home … to me, that would be a major game changer.  Such benefits would allow the person with AD to enjoy a much better quality of life for a much longer period of time. 

If Biogen follows through on its current plans, this will the first time that a company has ever ended a “failed” Phase III clinical trial of an experimental AD medication … then re-analyzed additional data … then claimed that this additional data support effectiveness of its medication … and then requested submission to FDA for approval to market.  After reviewing the research findings submitted by Biogen, the FDA can approve the medication, reject the medication, or find some evidence of effectiveness … but not conclusive enough evidence to warrant approval … and require additional clinical trials.

As a former AD spouse caregiver, I hope that the FDA will concur that aducanumab can be that major AD game changer after reviewing data submitted by Biogen.  But, until the FDA makes a decision, I will remain skeptical.  Biogen announced that it plans to report their new data and seek approval from the FDA in “early” 2020.  Stay tuned!