The FDA approved 2 new medications in the last few days. Are these additions truly medical advancements, otherwise known as “gamechangers”? What about the drawbacks?

DRUG #1

A 2.4 mg /week subcutaneous dose of the glucagon-like peptide (GLP-1) receptor agonist semaglutide (Wegovy by Novo Nordisk) has been approved for weight loss. Indications: to be used as an adjunct to a reduced-calorie diet and increased physical activity for adults with obesity.

This medication works by reducing hunger while promoting feelings of fullness. It is being hailed as a paradigm changer in the war against weight loss.

The favorable decision is based on results of a four phase 3 clinical trials that tested the drug’s efficacy and safety in more than 4,500 patients who were randomized to receive a reduced calorie meal plan and an exercise program OR the lifestyle intervention plus semaglutide. Studied subjects attained a 15-18% weight loss over 68 weeks.

What’s interesting is that this is not a new drug. Under the name of Ozempic, it is used in control of type 2 diabetes. However, the dose studied for weight loss is significantly higher.

Drawbacks include GI side effects including nausea, vomiting, and epigastric distress from fullness. Side effects such as abdominal cramping, constipation and diarrhea can be exacerbating symptoms in those who suffer from irritable bowel syndrome. Then there is the subject of cost which is estimated to be about $1350 which more than likely will not be covered by insurance.

This is not a small deal. With 70% of the US population overweight and 42% obese, we are clearly losing the battle of the bulge. There may well be a role for this medication (first weight loss drug introduced since 2014). The hope is that it might also cut down on attendant diseases such as heart disease, hypertension, lipid abnormalities, cancer and diabetes often seen in the obese population.

My view: I don’t think of this as a miracle drug, but it could represent a paradigm shift in weight loss drugs where we target the gut as opposed to the brain. However, this shift should NEVER be a solution without altering lifestyle (diet and exercise), which remains my modus operandi.

DRUG #2

A 170 mg monthly intravenous drug aducanumab (Aduhelm by Biogen), has been approved for Alzheimer’s disease. This is a monoclonal antibody that selectively binds to accumulated amyloid plaque in the brain (a hallmark of Alzheimer’s disease).

This medication is certainly more controversial, than the weight loss drug discussed above. Two trials EMERGE and ENGAGE were terminated 3/2020 when it became obvious that the drug was unlikely to outperform placebo. Then in 11/20, in an ongoing battle with Biogen, the FDA overwhelmingly voted against the drug, after a second analysis determined that positive results were seen in only one of the two trials.

CONFUSED YET?

The FDA eventually approved the drug earlier this week through the agency’s accelerated approval pathway (a fast-track method). This allows the approval of a drug for serious conditions that fill an unmet need. This approval assumes but does not prove that the drug will produce a clinical benefit. The endpoint here is the ability for the drug to reduce beta-amyloid in the brain.

What we know is that there have been several anti-amyloid drugs in the past that reduced plaque but showed no benefit on cognition.

Well, Aducanumab might have been approved, but Biogene is required to conduct a post-approval trial to demonstrate clinical benefit. If expectations are not met, the FDA may withdraw the drug’s approval.

Does any of this make sense? Here a drug is marginally approved via fast track after being denied such status just a few months prior. And the conditions for ultimate approval are great.

Aducanumab is to be administered intravenously every 4 weeks at a cost of about $56,000 per year. Not included is the price of ongoing MRIs, which the FDA advises to monitor patients.

Now accelerated approval based on ongoing clinical benefits requiring a confirmatory trial is not new. It’s been used in the past for cancer drugs.

The problem as I see it is that functional medical practitioners like myself see Alzheimer’s disease as a multipronged disease. There more than likely will never be a medication that will either reverse the disease or stop it in its tract. Many believe that the deposition of amyloid plaque in the brain is more likely the body’s response to quell ongoing inflammation.

My view: There appears to be too much hope on a drug to alter the course of Alzheimer’s disease. There is more to this disease than amyloid plaque. Let’s not forget about diet, exercise and lifestyle. There are several integrative neurologists that believe Alzheimer’s can actually be prevented.

So here you have 2 new medications approved within one week. You will no doubt be hearing a lot about these soon. Keep an open mind. As a Medial Advocate, do your part to stay in the driver’s seat as it relates to your health.

 Links to articles referenced:
A Drug to Treat Alzheimer's Was Approved. Now What?
FDA Approves 'Game Changer' Semaglutide for Weight Loss