Whatevever Happened to Filbanserin, the "Female Viagra" Drug?

Last year we were talking about a new libido drug for women, called filbanserin (see this blog, July 2, 2015.). The drug was supposed to improve women's sex lives, giving them the same options men have had for years with Cialis and Viagra. The drug was poised for approval by the FDA, even though there were concerns that it wasn't very effective. Whatever happened to it?

The story of filbanserin (trade name Addyi) is one of hype, greed, and mismanagement. filbanserin was originally under development as a drug to treat depression. Then it was discovered that it seemed to improve some women's satisfaction with their sex lives. Sensing that there might be a really big market for the drug, a small company called Sprout Pharmaceuticals bought the rights to the drug. Twice they tried get it approved by the FDA. When filbanserin was finally approved last August, the company's sales force of 14 national/regional sales managers and 150 sales representatives was all set to promote and sell the drug.

But just one day after FDA's approval of filbanserin, Sprout Pharmaceuticals was bought by an even bigger pharmaceutical company, Valeant Pharmaceuticals for (wait for it...) a whopping $1 billion. (Big fish swallows helpless little fish.) Valeant was making a name for itself on Wall Street by buying up other smaller pharmaceutical companies with patented drugs and immediately raising the drugs' prices. Yes, that's the same Valeant Pharmaceuticals that is now under federal investigation for predatory drug pricing practices.

Valeant's stock price has plummeted 85% since last year. As part of its efforts to save itself, Valeant dismissed the entire Sprout Pharmaceuticals sales force and shelved all plans to sell the drug, saying they might reintroduce the drug later this year. We'll see.

Only a few thousand prescriptions for the drug were ever written. Forget about it: it wasn't a very effective drug anyway.

Determining Who Can't Tolerate Statins

For years now, a class of drugs called statins have been the treatment of choice for lowering LDL cholesterol levels. They're cheap (pennies a day), effective, and safe. The problem is that 5-20% of patients say they can't tolerate the statins because of muscle-related side effects, including muscle pain and weakness.

A new class of class cholesterol-lowering drugs, called PCSK-9 inhibitors, avoids the muscle-related side effects. However, the big downside to the PCSK-9 inhibitors is that they are very expensive - approximately $14,000 a year. For that reason, insurance companies would like the PCSK-9 inhibitors to be used only by the few people who are truly intolerant of the statins. But how is intolerance to the statins to be defined, other than by the patients and their physicians?

A recent study showed how big a problem this is. Researchers wanted to explore the effectiveness of several newer LDL cholesterol-lowering drugs in statin-intolerant patients with very high cholesterol levels. To find such patients, they recruited more than 500 patients who had tried two or more statins and claimed that they could not tolerate them because of muscle pain or weakness. The patients were randomly assigned to take a statin (atorvastatin) or a placebo for ten weeks. Then the drugs were switched for an additional 10 weeks. It turned out that only 43% of the patients could be defined as statin-intolerant; that is, they reported muscle-related symptoms while they were on the statins but not while they were on the placebo. 26% of the patients reported muscle pain only while on the placebo, 17% never experienced muscle-related symptoms on either the statin or the placebo, and 10% complained of pain on both the statins and the placebo.

The bottom line is that fewer than half of all patients who say they are statin-intolerant actually are statin-intolerant. Because the PCSK-9 inhibitors are so expensive, some insurance companies are suggesting that patients who request them should be tested for statin intolerance (as the patients in the above study were) before insurance will pay for the new drugs.

What do you think? Should patients be required to submit to several months of testing before their (and your) insurance company agrees to pay for a $14,000-a-year drug for them?

A "Liquid Biopsy" for Lung Cancer

There are several known possible genetic mutations in non-small cell lung cancer (NSCLC), the most common form of lung cancer. Depending on which of several mutations it is, the cancer cells will respond differently to different treatments. The problem is that in the past the only way to tell which type of genetic mutation was present, and hence which treatment would work best, was a biopsy, which is invasive and often painful. A biopsy is certainly worth doing, of course, if it's required for adequate diagnosis and treatment, but not if there were an easier or better way.

Now scientists may have found that easier way. When cancer cells die (or when any cells die, for that matter), their DNA is spilled into the blood. By testing a sample of the patient's blood for the various possible genetic mutations found in NSCLC cells, it should be possible to identify the specific genetic mutation present, and thus to know which of several treatment options is likely to work best.

That's precisely what research conducted at the Dana Farber Cancer Center in Boston has found. The researchers have identified two key genes found in NSCLC cells using just a single test tube of blood. Technically known as plasma genotyping, the new test is also referred to as a "liquid biopsy" because it serves the same function as a traditional tissue-based biopsy, only using a liquid (blood).

In addition to helping physicians determine which of several treatment options to offer the patient, the liquid biopsy can also be used to determine how well the patient is responding to the treatment. If the cancer treatment is working, for example, the unique genes found in NSCLC cells should begin to disappear from future liquid biopsies.

Exercise Doesn't Increase Bone Strength

It's a commonly-held belief that weight-bearing exercise is a good way to increase bone density and strength. But it isn't true. The notion comes from the fact that you do lose bone mass if you are bed-ridden for a long time (or if you are an astronaut in space). But the inverse idea; that you gain bone mass when you exercise, doesn't seem to be true, according to an article in The New York Times that summarizes recent research. The available research shows that exercise only increases bone mass about 1% - not enough to have much effect on overall bone strength. Apparently, just the effects of gravity on your normal types of activity are enough to keep your bones healthy.

However, exercise does reduce the risk of bone fractures, especially in older people. Apparently that's not due to stronger bones, but to better balance and/or stronger muscles, both of which reduce the risk of falling.

The First U.S. Uterus transplant Has Failed

The first attempted uterus transplant in the U.S. has failed. The patient, Lindsay MacFarland, appeared before reporters on February 26, two days after the operation, to thank The Cleveland Clinic and her doctors. But just a day later the uterus was removed because of complications caused by a yeast infection. The announcement of that failure came only yesterday. For more details and photos, see the article in the Daily Mail.

The Cleveland Clinic had anticipated that this would just be the first of ten such surgeries in order to evaluate the potential of such transplants on a wider scale. The protocol may have to be modified in an effort to reduce the chances of future failures.

As I noted in a previous post (see this blog, Nov. 23, 2015), a uterus transplant serves no valid medical purpose other than to allow an infertile woman to experience pregnancy. In a statement to the New York Times last year Mrs. MacFarland, the mother of three adopted children, said, "I crave that experience. I want the morning sickness, the backaches, the feet swelling. I want to feel the baby move. That is something I've wanted for as long as I can remember. "

Do you think it will be worth the risk and expense for surgeons to perfect this surgery? (Mrs. MacFarland's surgery was paid for by a government-funded research study.)

Easier Access to the Morning-After Pill? Not in Arizona!

Just last week the FDA established new labeling guidelines for the use of mifepristone, the so-called "morning-after pill" (see this blog Apr. 1, 2016). The new labeling guidelines were expected to make mifepristone more widely available in six states that had specifically passed laws requiring physicians to adhere to FDA labeling guidelines when using the drug. The previous labeling guidelines written in 2000 are no longer considered "best medical practice". But they were much more restrictive than the way most physicians were using the drug, so in effect they limited access to medication abortions.

But wait a minute! Just one day after the FDA established the new labeling requirements for mifepristone, Arizona's governor signed into law legislation that declares that mifepristone may only be used in accordance with the old protocol as it existed at the end of 2015. The new law will take effect this Summer, when the legislature is conveniently out of session. Apparently the Arizona legislature knew the FDA ruling was coming and made a preemptive strike against it before adjourning. The intent is clear, for there can be no medical justification for sticking to an outdated protocol that restricts access to a safe and effective drug.

We'll see how this plays out in the courts and in other states that may choose to copy this approach. At the very least, it is likely to delay the availability of mifepristone in Arizona by a year or so.

For more on this subject, see the article in The New York Times.

A Temporary School Closure Due to Measles

A single case of measles in a preschool student in California has prompted the county's Public Health Department to close the preschool for several days. In addition, the health department has informed all parents that children who are not fully vaccinated will not be allowed to return to school for an additional week and a half, even though the school will be reopened for vaccinated students.

Measles is a highly contagious disease. Although most infected individuals recover fully without incident, measles still causes an estimated 140,000 deaths worldwide per year. Health officials stress that approximately 95% of the individuals in any community need to be vaccinated in order to achieve "herd immunity", in which the disease is not able to spread rapidly throughout the community once an individual is infected. Vaccination rates are well below that number in some counties in California.

Reading between the lines, this may be a situation where the health department has exercised its authority and fired a warning shot across the bow of parents who have (so far) refused to have their kids vaccinated. California passed a law last year that requires children to be vaccinated in order to attend school (see this blog July 8, 2015). The law, which takes effect on July 1st for this year's crop of preschoolers, no longer allows for exemptions based on personal or religious beliefs. At the school in question only 43% of the children have been fully vaccinated, according to the Huffington Post. If they are not vaccinated by this Fall they will have to be home-schooled.

Anti-vaxxers may be in for a tough fight on this issue. Their main argument against vaccinations seems to have shifted recently from "vaccines cause autism" to "it's a matter of choice". But they do not have the choice to endanger the health of others, according to the State of California.

New Guidelines for the Use of the Morning-After Pill

The FDA has published new guidelines for the use of the "morning-after" pill mifepristone (MifeprexR), used to affect a medication abortion. The new guidelines will permit the pill to be used up to 10 weeks after pregnancy, three weeks longer than previously permitted. The new guidelines will also require only two visits to a physician for a full course of treatment, making the drug easier to obtain and use. Many doctors had already been using mifepristone according to the new guidelines (meaning that they were using it "off-label" at the time), because it has been known for years that the pill is safe and effective up to 10 weeks after pregnancy.

The new FDA guidelines are a setback for the anti-abortion movement. In an effort to make access to mifepristone as difficult as possible, anti-abortion advocates had convinced the legislators of six states (Arizona, Arkansas, Ohio, Oklahoma, North Dakota, and Texas) to pass laws prohibiting off-label use of the drug. The unspoken goal of these laws was to make it harder to obtain and use mifepristone by forcing patients to see a physician three or more times instead of just twice and limiting the drug's use to just seven weeks after pregnancy. The tactic worked; one study found that medication abortions fell by more than 80% in Ohio after introduction of the restrictive law in that state, according to CBS News.

Under the new guidelines, the way that most physicians currently prescribe mifepristone will no longer be "off-label".  As a result, medication abortions should again become more common in those six states that had attempted to restrict them.