Why You Should Avoid Another Lousy Flu Drug: Xofluza

A new medication has been approved by the Food and Drug Administration to treat influenza.  Xofluza (Baloxavir).  It is an antiviral medication approved in October, 2018, by the FDA to treat infections from influenza A and B.  Studies have shown it may reduce the duration of influenza symptoms by about 24 hours.

Xofluza is the latest anti-influenza medication approved by the FDA.   The earlier anti-flu medications are neuraminidase inhibiters.  I wrote to you about the failure of this class of drugs in a previous blog post (http://112.196.20.91/drbrownstein/forget-tamiflu/).  Tamiflu, working by a different medication than Xofluza, was shown to decrease influenza symptoms by about 21 hours.

As I said in that earlier post, “Folks, I can’t make this stuff up.”

Remember, the US government bought and stockpiled millions of doses of Tamiflu in case there was an influenza crises.  Tamiflu costs about $120 for a full course of treatment.  Xofluza costs $150 for a full course of treatment. (Note:  Tamiflu and Xofluza both are treated as a one pill regimen to be taken within the first 24 hours of influenza symptoms.)

In 2014 I wrote this about Tamiflu:  “Tamiflu, the widely prescribed antiviral drug for the flu, is surprisingly still on the market.”

The reason I wrote that statement is because Tamiflu is an expensive, ineffective drug that has too many side effects.  As I stated above, it only reduces flu symptoms by slightly less than 24 hours.  And, here are the side effects associated with Tamiflu:  nausea, diarrhea, and headaches.  Yes, you read that right:  the same symptoms caused by the flu are caused by the $120 anti-anti flu drug Tamiflu. Tamiflu was never shown to affect the number of hospitalizations or other complications from the flu including bronchitis, pneumonia, sinusitis and ear infections. As if that is not enough, Tamiflu is also associated with renal and psychiatric events and can induce heart rhythm problems.  How Tamiflu got approved and how it still stays on the market is beyond my comprehension.

Let’s get back to Xofluza.  The FDA approved Xofluza after a study was published in the September, 2018 edition of the New England Journal of Medicine.   Guess who funded the study?  If you guessed the same Big Pharma company that developed Xofluza, you win the prize.  The article concluded, “Single-dose  {Xofluza} was without evident safety concerns, was superior to placebo in alleviating influenza symptoms…”

The September, 2018 NEJM study was the catalyst for the FDA to approve Xofluza.  Since Tamiflu, the blockbuster drug, doesn’t work so well, I was interested to see how effective Xofluza was shown to be and what side effects were associated with it.

Like Tamiflu, Xofluza was shown to decrease the symptoms of the flu by about a day–26 hours.  So, here we have another expensive flu drug that may decrease the symptoms of the flu by about a day.  That might be worth a trial if there were no side effects.   The authors reported that adverse events with Xofluza were reported in 23-27% of patients in the treated groups and 29% of the patients in the placebo group.

Read that last sentence again:  the placebo group had more adverse effects than the Xofluza-treated group. How can that be?

The adverse events in the Xofluza-treated group included diarrhea, bronchitis, nausea, headache, and vomiting.  Astonishingly, the placebo group had more adverse effects in nearly every category.

Folks, after reading the adverse event data, what do you think the next logical question should be?  Here’s what should be asked next: What the heck is in the placebo that is causing so many adverse effects?!  You see, a placebo is supposed to be an inactive substance that causes no physiologic changes.  An inert placebo is supposed help discern not only the effectiveness but also the toxicity of the drug being tested against it.  If you use a placebo that causes adverse effects, it allows Big Pharma to state there were no safety concerns with the drug (since the adverse effect profile was similar or better than the  placebo).

By the way, Big Pharma has been using this same dirty playbook for years in vaccine research.  They test a vaccine against a reactive substance or another vaccine and when the adverse event profile is similar, they state that the vaccine is safe and has little or no side effects. But, I digress.

By now, you should be irritated. I know I was when I looked at this data.  I pored over the NEJM article looking for what was in the placebo.  It was not included anywhere including the supplemental index.  My irritation level increased after I spent an inordinate amount of time trying to figure out what the contents of the placebo were.

So, I decided to email the lead author.   The lead author had no idea what was in the placebo and referred me to “Shionogi colleagues for response.” The first email from the Shionogi colleague stated,

“Dear Dr. Brownstein,  Thanks for your question. Since this contains confidential information, please accept limited information can be shared with you. We used film-coated tablets (with comparable appearance to baloxavir tablets) consisting of ingredients, such as D-mannitol, microcrystalline cellulose, and magnesium stearate.”

I was not happy with that email response.  Since when are the ingredients of a placebo classified as “confidential information?”  If I were the peer-reviewer of the article I would never have let it pass without divulging the full ingredients of a placebo which caused more side effects than the drug being tested.  In fact, I would recommend that the researchers redo the study with a true placebo.

Microcrystalline cellulose and magnesium stearate are relatively benign substances to most people unless they have an allergy to it.  I would not expect D-mannitol to be in a placebo for a flu drug study since the “common” side effects of mannitol include:  nausea, vomiting, fever, chills, headache, and runny nose.

Do these “common” side effects sound like a common illness (i.e., influenza)  that circulates yearly in our population?  If you want to make a poorly performing flu drug appear better than it actually is, compare it to a placebo that causes flu-like symptoms.

To be fair, mannitol is used in some supplements and food sources as a coating.  Maybe mannitol is not the real issue here.  Maybe there is something else in the placebo that is causing so many problems.

Needless to say, I would not recommend taking Xofluza for influenza.  It may give you a few hours respite from the flu, but It has not been properly studied.  It would be appropriate to have an independent study not funded by Big Pharma where a true placebo is used.  I hope the US government does not decide to spend hundreds of millions of dollars on stockpiling another ineffective flu drug. Furthermore, I hope you don’t spend $150 on a poorly studied ineffective flu drug.

If I hear anything more from the researchers, I will be sure to let you know. ~DrB

Addendum: I was ready to publish this post last night when a late email came in from Shionogi. Here’s what was written in the email:

Dear Dr. Brownstein,
This morning I got the confirmed information from my colleagues. Those listed below are components used in the placebo tablets for baloxavir.
We hope these information addresses your inquiry.
D-Mannitol
Crystalline cellulose
Magnesium stearate
Hypromellose
Titanium oxide
Talc

I then asked for a breakdown of the amounts of each ingredient in the placebo. Here is the exchange (the first email is my response to Shionogi):

Dear Dr. XXX
Thank you. Can you tell me the exact amounts of each ingredient? Thank you, D. Brownstein, M.D.

Dear Dr. Brownstein,
Thanks for your further inquiry. Unfortunately, I confirmed that the Company require an execution  of CDA {confidential disclosure agreement} for more details. If you don’t mind, we can proceed with a paper work with more details in your side.

So, in order to find out what was in a placebo, it took multiple emails, lots of time, and I need to sign a nondisclosure agreement. How does this happen? Why isn’t the FDA forcing these companies to put this information out there? How does Big Pharma get away with this stuff? Does this change anything I wrote in the post? No way! The placebo is suspect and I would not recommend taking it. In fact, the placebo looks poorly designed, IMHO. ~DrB

Author Info

David Brownstein, M.D.