Conquering COVID Part 2.3 (aka the 14^th Installment in a Finite Series):

“Xofluza vs. Tamilfu - who really wins against the flu (influenza)?!”

(aka hint: we are all winners in this symbolic battle)

August 10, 2020

(Note: All references are at the end of the column now-thank you).

Okay, can I just be super-duper (that is more than average) honest here? Some of the strangest, cheesiest, and all out weird current TV commercials are for a few (noticed how I used the word “few” and not “all”) pharmaceutical drugs - many I have no real knowledge of because the commercials themselves have little to do with the medical conditions. Furthermore, at the end of these commercials, a fast-talking voice, similar to an auctioneer, tells me every single darn possible common, rare, and even super-rare side effect that you can potentially experience from these medications, and I can never memorize them all because the list is too long, and too fast! Wait, did he/she say just say “belly button leakage?” (okay, I made up that side effect for levity).

Yet, what is perhaps even more strange is the LACK OF ANY CURRENT TV COMMERCIAL for an anti-viral drug that does a heck of job fighting common flu, or influenza symptoms, and appears to provide tremendous protection against the flu when someone in the house has it, and you only need one dose at one time. Yes, you only take it for one day and at one time! Where is that commercial?! I have no idea because it was there for a month or so and then it disappeared!

Look, there are only two countries in the entire world that allow direct-to-consumer pharmaceutical advertising on TV, one is the U.S. and the other is New Zealand (ah, another interesting fact that you learn by reading this column). I was in New Zealand for work several years ago and I saw several pharmaceutical advertisements. By the way, I think my wife and I were the only ones in New Zealand as guests of one of their prestigious (notice how I inserted that word “prestigious” to make myself appear more important than I am) medical organizations that did not parachute or skydive or bungee jump when we were there, despite other doctors and health care folks telling us we “have to do this.” What is up (actually going down) with New Zealand and everyone wanting to do dangerous things to make themselves “feel more alive,” as many of their prestigious doctors specifically recommended?! I feel plenty alive and adventurous when I am cutting my toenails without my reading glasses, or when simply swerving to miss potholes while driving on almost every Midwest road! Heck, I also feel plenty alive by simply answering my cell phone from my kid in graduate school who I know is going to tell me he loves me over and over again, and then right before we hang up he will immediately segue into why he needs more money! Why do I have to go bungee jumping to feel more alive than I do right now?! My 155^th consecutive Us TOO column is due tomorrow … yes … 155^th consecutive (almost 13+ years) … but I thought it was due next week, so again I do not need any added stress and adventures! Anyhow, I digress. I apologize. Back to the

X-O-L-F-L-U-Z-A and the T-A-M-I-F-L-U battle and the bigger educational message.

Okay, let me preface the rest of this column by unequivocally stating that I have never worked for, been paid by, volunteered for, met, plan to work for, or even walked anyone’s dog for money at the company that makes the drugs Xofluza or Tamiflu. I just think it is a fascinating untold, unsung drug story that symbolically represents something even bigger (I will explain shortly)! Xofluza is the trade name of the drug also known as “baloxavir marboxil.” It is what is known as a “polymerase acidic (PA) endonuclease inhibitor” (say that 10 times fast for a giggle and to impress your socially-distanced friends), and it blocks the ability of the influenza virus to replicate at an early stage in the process - ergo it is an ANTI-VIRAL pill that fights influenza A and B. It is FDA approved for acute uncomplicated influenza in patients 12 years of age or older who have been SYMPTOMATIC FOR NO MORE THAN 48 HOURS. AGAIN, THIS IS FOR THE FLU OR INFLUENZA (not for COVID-19 right now). If you get a prescription from your doctor, then you just take a single dose within 48 hours of symptom onset. You can take the pills with or without food (although food can reduce the absorption of the drug). Interestingly, you are NOT supposed to take these pills with dairy, calcium-fortified beverages, some laxatives (known as polyvalent cation-containing), antacids or dietary supplements including iron, zinc, selenium, calcium or magnesium, because these things could impact the efficacy of the drug. The dosages you take DEPENDS ON YOUR WEIGHT, so if you are approximately 88-174 pounds (40-79 kg) then the dosage is two 20 mg tablets taken at the same time. And, if you are at least 175 pounds (80 kg) then you are supposed to take two 40 mg tablets at the same time. Wait? That’s it? Yes! That’s it! Does that mean you do not need a flu shot? Nice try. You still need your flu shot because this new pill is for symptoms of the flu under the supervision of your doctor. If you are under 12 years of age, or less than 88 pounds (40 kg), then there is no research in this area. I apologize for mentioning all this kilogram stuff but according to the Metric Conversion Act that was signed into law on December 23, 1975 (no kidding) we are all supposed to be moving toward the metric system in the United States. So, 45 years later I am still NOT comfortable with the metric system, and when I drive on the highway the signs still tell me the number of miles to Chicago, Detroit, or Florida in miles and not kilometers, so I am not optimistic about this metric transition anytime soon. Although, my personal body weight sounds lower and looks lower in kilograms compared to pounds (1 kilogram = 2.2 pounds) so perhaps I will just use the metric system when reporting my personal body weight. Sorry, I once again digress! Darn!

“Wait, there is more!” (sorry, I like to watch late night TV commercials). Research just published in the New England Journal of Medicine has found that Xofluza could have a dramatic ability to prevent clinical influenza or complications of the flu in household contacts, or those exposed to a person in the house with ongoing flu, and perhaps even regardless of the size of the household! For example, if I have the flu and I do not want my wife to get it (notice the selflessness of that example - I accept the flu for me but not for my wife … what an amazing husband I am!). In a clinical trial of approximately 750 household contacts of 545 index flu patients, Xolfuza resulted in the flu in 1.9% versus 13.6% with placebo in those household contacts (the ones being exposed to the person with the flu in the same house), which is an impressive 86% reduction (p<0.001)! Just from taking one dose of the anti-viral on one single day! Xofluza was also found to be potentially effective in high-risk, pediatric, and other subgroups, and the SIDE EFFECTS WERE SIMILAR BETWEEN DRUG and PLACEBO! A total of 374 individuals took Xofluza in this study (from the 2018-2019 Japanese flu season) and 375 took placebo. The basic side effect rate of the drug (adults and adolescents), in general, is the following: diarrhea =3%, bronchitis=2-3%, nausea=1-2%, sinusitis=2%, and headache=1%. Not bad, and incredibly low for an anti-viral drug.

Okay, Dr. Moyad cut to the B.S. (bogus science)! What is the real catch? In my opinion, there is one major virtually unmentioned catch - it needs to be studied more in people recently or currently dealing with cancer! It might or might not be an amazing option, and it has been recently (actually October, 2019) FDA approved for people at higher risk of getting and dealing with the flu, including those with: asthma, chronic lung disease, diabetes, heart disease, morbid obesity, or adults 65 years of age or older. But what about cancer patients?! You see there is virtually little-to-no mention of this issue because there has not been enough research in this area, which is why I decided to write about this interesting topic. Anyhow, other groups are studying this issue right now, so please stay tuned and ask your doctor for a research update if you are dealing with the flu and need a pill.

What are the other catches? Xofluza may or may not work better than Tamiflu (also known as “oseltamivir”) - another popular anti-viral pill used for the prevention and symptoms of influenza (also within 48 hours of symptom onset). Tamiflu was first approved in 1999 and in 2016 the FDA approved a generic Tamiflu option. Tamiflu is usually taken once or twice a day for five (treatment), or at least ten days (for prevention in a high-risk situation or exposure…). It works in a different way than Xolfuza and a little bit later in the viral process, which is one reason why you may need a longer duration of use. Another major catch is the cost of Xofluza. It can cost around $150-160 to take this drug with a coupon, from goodrx.com, for example, or if it is not covered by your insurance. Although, the official Xofluza drug website has a nice coupon you can download. Tamiflu is only $25-50 with a coupon if it is not covered by insurance, and it is FDA approved for ages two weeks and older for those that qualify. Seriously, cancer patients are at a higher risk of running into serious complications if they get the flu, so they need to know they have options out there when feeling symptomatic and their doctor thinks/knows it is the flu. Flu vaccines are great, but in some cancer patients they do not work as well, so they need additional options after being vaccinated, just in case they are dealing with the flu, or when potentially exposed to someone with the flu in the same local environment. Tamiflu is an option in some cancer patients if the doctor approves it. Xofluza keeps accumulating interesting research, and we all need to follow the latest research. One concern in immune suppressed individuals is a potential for an increased risk of drug resistance but, again, this should be worked out between you and your doctor, and not some entertaining and informative column on the internet.

I am just really excited about two potential options to talk with your doctor about this upcoming flu season, because with COVID-19 there is also a concern about co-infection, or getting the flu during a time where COVID-19 is happening. In other words, this column is about raising awareness and education so cancer patients dealing with these options, and their family members, and even those without cancer know how to better protect themselves. So, the real goal here is that if YOU OR OTHERS ARE EXPERIENCING FLU SYMPTOMS, OR MAY BE EXPOSED TO SOMEONE WITH THE FLU, PLEASE TALK TO YOUR DOCTOR ABOUT THE PROS AND CONS OF XOLFUZA OR TAMIFLU AS A POSSIBLE OPTION TO FURTHER PROTECT YOURSELF. The drug has reduced symptoms by approximately one full day and even more in clinical studies compared to placebo, which is pretty darn good. And the earlier you use it when you qualify, the better the potential diverse results. Ongoing research suggests that Xofluza can reduce viral shedding in some folks within one day of taking it, so they are potentially less likely to transmit or experience the devastating effects of influenza. Reducing viral shedding is critical because it appears that, in more immune suppressed folks, viral shedding occurs for longer periods of time, which is dangerous to that person and those around them. Now, let us move on to the larger Moyad lesson of this column!

There is no data to suggest these drugs impact COVID-19, but there is a larger general lesson here to discuss that has little to do with these drugs and more to do with anti-viral pills in clinical trials right now. THERE HAVE BEEN PAST AND RECENT EXAMPLES OF VIRUSES THAT WE THOUGHT COULD BE DEFINITELY CONQUERED BY A VACCINE, BUT NEEDED A PILL TO COME TO THE RESCUE TO TREAT AND POSSIBLY PREVENT THESE TERRIBLE VIRAL INFECTIONS! THIS WAS THE CASE WITH HIV AND HEPATITIS C! Many researchers were convinced we could eventually get a vaccine that would create a strong and durable enough immune response to prevent these infections, but the virus was tricky, so our own immune system had a tough time of being primed or winning the battle against these infections! Well, lifesaving pills (anti-virals) saved the day and are still the treatment of choice today because we still do not have a successful HIV or Hepatitis C vaccine. There are even anti-viral pills for HIV prevention available right now, and they have amazing efficacy when taken daily in those at high risk of being infected! Wow! Imagine if we had that for COVID-19! If it was safe and effective would I take it? You’re DARN (I wanted to use another word there, but decorum does not permit it) right I would!

So, we have become fascinated with COVID-19 vaccines and multiple major companies are moving into final phases of testing, and there is tremendous optimism that this vaccine research will save the world when it comes to conquering COVID-19. Heck, I am one of those researchers, but I also know that we have to be confident and optimistic, but simultaneously humble and always have a backup plan. What if the vaccines are not as effective as we think they are going to be against the virus that causes COVID-19? The answer also comes in the form of antiviral medications or pills that you can take for prevention, or when experiencing symptoms! This would not only help you, but also others around you, because it would reduce transmission of the virus! There are countless clinical trials going on right now with numerous anti-viral drugs and even supplements. I am just as excited about these anti-COVID-19 pills as I am with the vaccines, because, again, research and public health teaches us to be modest and “when in doubt, try and eliminate the doubt.” In other words, you just cannot bet everything on antiviral pills or vaccines, but both options and, of course, other preventive and treatment methods. During a pandemic you have to throw almost everything against a viral wall to see what sticks! In fact, did you know that recent research from the CDC and others demonstrated that even Tamiflu could have shown efficacy against the 1918 global influenza pandemic!? Of course, some resistance would have emerged, but the more antiviral pills the better the chances of success! Some people love to go negative with antivirals like Tamiflu, with claims of inefficient efficacy, or more cons versus pros for certain healthy folks. But, in reality, Tamiflu was just a first step in preventing and treating vulnerable populations of people from being exposed and impacted by a potentially terrible disease. Xofluza is another step in the right direction and, heck, even studies right now are testing the combination in hospitalized patients. Anti-virals need more attention in the world of cancer and other vulnerable populations, but they also represent another option against many diseases that we thought only a vaccine could completely conquer!

Thank you for reading my latest installment and I wish you and your family the best of health. I am concerned, of course, but I am also incredibly optimistic! I look forward to modern day science and you of course, kicking COVID-19 and cancer in the gluteus maximus!

All of my best always,

Mark A. Moyad MD, MPH