Risk v. Benefits in Drug Treatments


How much risk are we willing to accept for better health? This important question must be answered every day of our lives. It must be answered by everyone who decides whether or not to get the Covid vaccine. But often the government won’t let us decide. They believe they know better.

This issue has become front and center in the public debate as the Biden administration pulled the Johnson & Johnson Covid vaccine off the market because of rare blood clotting cases observed in less than one in a million vaccine recipients. Many scientists and doctors questioned this decision since the risks didn’t seem to outweigh the benefits. The six women out of over seven million Americans who received the J & J vaccine were all in the child-bearing age range and may have been on contraceptive medications that can cause the same complications. Further investigation will answer these and other questions, but should the rest of the population be denied this life-saving vaccine for the sake of so few?

As the government “pauses” to investigate the J & J vaccine, another important decision is in the making regarding new treatment for Alzheimer’s disease. More than six million Americans suffer from Alzheimer’s disease, according to The Wall Street Journal editorial board. This number is expected to soar as the baby-boomer generation gets older. Any family touched by this disease knows the heartache of progressive memory loss, abnormal behavior, and inability to perform everyday tasks.

While the cause of this disease is unknown, brain scans show the buildup of amyloid plaque and tangles of tau proteins, which typically begins decades before patients show cognitive problems. Hypertension, obesity, diabetes, smoking, poor sleep and the APOE4 gene variant put people at higher risk. While some medications can temporarily improve memory, attention, or mood, none slow the neurological and cognitive degeneration.

The search for effective treatment of this dread disease has intensified. Some 10 to 20 clinical trials on Alzheimer’s drugs have been initiated each year since 2008. Aducanumab, a monoclonal antibody drug, is the first disease-modifying medicine to show efficacy. It works by targeting specific molecules on the amyloid to clear plaque. While more than 25 trials on medicines employing this strategy have ended in failure, the manufacturer, Biogen, has learned from their mistakes.

The company used PET scans, normally used to follow cancer treatments, to screen trial participants to ensure they had Alzheimer’s – rather than other forms of dementia and were not in advanced stages of the disease. This filtered out patients who wouldn’t benefit from the drug treatment. As a result, a late-stage trial showed a high-dose treatment removed 71% of the plaque build-up after 18 months and also had a significant impact on disease progression. After 78 weeks of treatment, patients receiving a high dose were 84% less of a burden to care givers than were the controls. They showed a 91% smaller decline in the ability to prepare a meal and 39% smaller reduction in capacity to discuss current events.

This exciting news was met with skepticism because of the long history of failed Alzheimer’s medicines. The skeptics cite a second concurrent late-stage trial by Biogen that indicated aducanumab didn’t have a statistically significant benefit on symptoms. But Biogen reviewed these results and discovered a likely reason for the different outcomes. The two trials had nearly identical designs, but patients in one received the high dose longer, and the benefits increased with time.

Biogen worked with FDA scientists to analyze the discrepancies between the two trials. The FDA noted in June 2019 that the evidence from the positive trial could be “considered exceptionally persuasive.” Biogen applied in July for drug approval. Many physicians and groups that work with Alzheimer’s patients have urged the FDA to approve the drug. To date this has not happened.

Why is it taking so long for approval of this significant breakthrough in Alzheimer’s treatment?

The simple answer is the inefficiency of the FDA. The FDA empaneled a group of scientists to advise it in November – none of whom specialize in treating Alzheimer’s disease patients. They accused Biogen of massaging the data to favor approval. They urged the FDA to require Biogen to conduct another trial – which could take five or more years.

Three of the panelists wrote in the Journal of the American Medical Association to suggest that the FDA’s “unusual degree of collaboration” with Biogen could have “potentially compromised” its objectively. Ironically, this degree of “collaboration” was responsible for the rapid development of the Covid-19 vaccines under the Trump administration. Could it be that the current FDA, under the Biden administration, is pushing back for political reasons?

Imagine your reaction if your spouse is suffering from early Alzheimer’s disease and you know there is a potential new drug for treatment that could substantially reverse the disease? What harm could be done to someone who is rapidly deteriorating before your eyes, especially when there is no other known treatment? A similar situation arose recently with the development of Sarepta’s drug for Duchenne’s muscular dystrophy and an extended-release opioid by Zogenix.

The FDA has an important role to play in the development of new pharmaceuticals. They must weigh the risks v. benefits in any new treatment. The current climate of the FDA seems to outweigh risks and neglect potential benefits, especially in the case of diseases without other known effective treatments. The impact of success could be substantial, not only in the lives of those families impacted, but also in healthcare system savings that would easily reach the hundreds of billions of dollars.

The WSJ editors say, “The U.S. may be on the cusp of an Alzheimer’s breakthrough, and the FDA’s first duty is to patients.”


What do you believe? Let me know your reactions.

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