Testimony of Dr. Mary Carol Jennings to the Reproductive Health Drugs Advisory Committee of the FDA on Gabapentin

Testimony by Mary Carol Jennings, MD

March 4, 2013

 

My name is Dr. Mary Carol Jennings and I speak today on behalf of the National Research Center for Women & Families.

Our nonprofit research center’s medical and public health experts analyze and review research to provide objective information to patients, providers, and policy makers.  We do not accept funding from pharmaceutical companies so I have no conflicts of interest.

I trained in obstetrics and gynecology at Boston University Medical Center.

Like all of you, I understand the need for safer alternatives to hormone drugs for hot flashes and symptoms of menopause. The question is: is gabapentin a safe and effective alternative, or will its use harm more patients than it helps?

The key to your decision today lies in the efficacy analyses agreed upon before these studies began.  FDA states that all three of the phase 3 studies failed to meet required statistical significance in reducing hot flash frequency from baseline to Week 12, and one study failed to show required significant reduction in severity from baseline to Week 12.

In other words, based on the company’s own acknowledged criteria for approval, the drug failed.

The data indicated a decrease in the frequency of hot flashes at week four, but that effect disappeared by week 12. Hot flashes may continue for months, so 4 weeks is completely inadequate.

The company conducted the most recent study using a longer, 2-week baseline, hoping to “minimize the placebo response.”  As those of you skilled in data analysis know, such manipulations in data analysis are not appropriate in clinical trials.

Since the benefits of this product are extremely questionable, let’s discuss its safety profile.

If it were absolutely safe for everyone, then perhaps the fact that it doesn’t really work would be less important to some of you.

Dizziness and related symptoms are the most common side effect, seen in one in four women.  Women in the gabapentin group were six times as likely to fall.

Women up to the age of 70 were included in these studies, and falling is dangerous in aging women: it can lead to broken bones and in turn to reduced life expectancy.

What about cancer? The data indicate a link to pancreatic cancer for male rats.  The company’s clinical trials recorded 5 cancer diagnoses for patients taking gabapentin, and none for placebo.  We agree that getting cancer within months of starting any medication is not conclusive evidence.  But the possible cancer risk can’t be ignored, especially given the limited benefits of the drug.

Gabapentin is an antiepileptic drug, and FDA warns that all drugs in this class have a higher risk of depression and suicide.

In 2009, the FDA asked the company to study suicidality in a third trial (p10).  During the trial and followup, the patients on gabapentin were almost 3 times as likely to show a risk of suicide compared to the placebo group.

The studies are too small to show a significant effect, but the difference is substantial and deserves further study.   And, to be ethical and improve the study design, women with a history of depression should NOT have been and should not be included in these trials.

In conclusion, hormone therapy can reduce hot flashes, but has rare but serious risks.  Based on the evidence provided, it’s not accurate to say that this drug significantly reduces hot flashes, but it has potential serious risks.

It is your job to decide if you think the evidence is solid enough to show the benefits outweigh the risk.

Warnings on labels and post-market studies are not enough to justify the sale of an ineffective drug that certainly can cause a fall, and possibly can cause a suicide attempt or cancer.

Given the lack of scientific evidence showing this drug works, please urge the FDA to reject this application until the company conducts research providing clear evidence of effectiveness and safety.