For those who may not recall, Qnexa is a combo treatment – it includes phentermine, which was part of the fen-phen cocktail that was yanked in 1997, and topiramate, which is marketed as the Topamax seizure med. But phentermine can be habit forming and is contraindicated for people with advanced arteriosclerosis, cardiovascular disease, or moderate to severe hypertension (see more about this below), while topiramate includes warnings about suicide and requires a patient pregnancy registry.

Nonetheless, Vivus has been a hot stock lately, partly because clinical trial data released last fall showed Qnexa helped moribdly obese patients lose an average of 14.7 percent of their body weight, compared with 2.5 percent on placebo. Another study of patients with high blood pressure, high cholesterol or diabetes found Qnexa yielded average weight loss of 13.2 percent, compared with 2.4 percent on placebo (see our recent post). Meanwhile, concerns about revisiting the fen-phen debacle appear muted.

Consequently, the initial reaction of one Wall Street analyst to the FDA documents released this morning is upbeat. “Overall, we believe the language in the FDA briefing documents to be fairly benign,” wrote Leerink Swann’s Steve Yoo, in a note distributed a short while ago, “but the FDA is requesting a pregancy category X label that would include contraindication in pregnant women and a warning/ precaution for females of childbearing potential.” Indeed, the FDA notes that “if approved, the person-years of exposure to (Qnexa) among women of child-bearing potential will be enormous.”

Vivus, by the way, is proposing a large outcomes trial if its drug is approved. Please continue reading below for some key points in the FDA documents…

The majority of the study subjects were middle-aged white women. The elderly, which was defined as those older than 65, represented less than 8 percent of the total study population. Overall, 12 percent of low-dose and mid-dose subjects, and 18 percent of high-dose subjects withdrew from the studies due to an adverse event.

The incidence of depression-related adverse events in clinical trials was 3.4 percent in the placebo group, 5 percent in the low-dose group, 3.8 percent in the mid-dose group, and 7.7 percent in the high-dose group. Anxiety-related adverse events were reported with frequencies similar to those observed for depression, with nearly three times as many reports in high-dose versus placebo. Sleep-related adverse events were reported by approximately 6 percent, 7 percent, 7 percent, and 11 percent of subjects randomized to the placebo, low-dose, mid-dose, and high-dose groups.

In Phase III clinical trials, subjects randomized to Qnexareported more cognitive-related adverse events compared with subjects randomized to placebo. When the attention, memory, language, and other cognitive disorders not otherwise specified subclasses were pooled, the incidence rates were 1.7 percent, 2 percent, 5.6 percent, and 7.8 percent in the placebo, low-dose, mid-dose, and high-dose groups, respectively. The clinical significance of these imbalances is unknown.

In categorical analyses, the Qnexa patients had greater frequencies of increases in baseline heart rate of 5, 10, 15, and 20 beats per minute compared with the placebo group. The clinical significance of the increases in heart rate is unknown. The incidence of arrhythmia-related adverse events was 1.8 percent, 1.3 percent, 4.2 percent, and 4.7 percent in the placebo, low-dose, mid-dose, and high-dose groups, respectively. Palpitations comprised the majority of these adverse events and occurred in 12 (0.8 percent) placebo subjects and 27 (1.7 percent) high-dose subjects.

Relatively few elderly individuals or subjects with a history of myocardial infarction or stroke were enrolled into the phase 3 clinical trials. Not surprisingly, then, the overall number of ischemic cardiovascular-related adverse events in the development program was very low.

Another issue is metabolic acidosis. The percentages of individuals from the placebo, low-dose, mid-dose, and high-dose groups who experienced two consecutive or an endpoint bicarbonate value below 21 mEq/L were 2.1 percent, 8.8 percent, 6.4 percent, and 12.8 percent, respectively.

And what about efficacy? The mean weight loss for patients on the high-dose was 10.6 percent, 8.6 pecent for the mid-dose and 5.1 percent for thos on the low-dose and 1.7 percent for patients given a placebo.

The Department of Health and Human Services and the Department of Justice were chartered with overseeing whether the states are meeting the qualifications that would allow them to receive a share of any proceeds recovered. And so last week, Senator Chuck Grassley, the ranking Republican on the Senate Finance Committee, who regularly probes drugmakers, wrote the agencies because only 14 states are up to speed (see the letter). However, hee’s also miffed that recent changes to the federal FCA may “undermine the original intent” of the law, and he cites proposed state laws that include a so-called first-to-file hurdle.

This would preclude a whistleblower from bringing a lawsuit if a similar lawsuit has already been filed in another state, which would have the effect of reducing the number of such lawsuits that would be brought against government contractors. “These provisions will severely limit qui tam actions brought by relators in states where the language is adopted,” writes Grassley, who wants the HHS Office of Inspector General and the Justice Deparment to review these proposals to determine whether passage would remove the incentives provided under the 2006 Deficit Reduction Act.

One wag says that pharma is behind the state proposals. “Pharma lobbyists have been running around trying to be ‘helpful’ by suggesting amendments that would cripple state False Claims Acts. It’s a bit like the fox suggesting the chicken farmer might want to swap out his shotgun for a BB gun,” says Patrick Burns of Taxpayers Against Fraud, a non-profit that supports whistleblower suits.

“If they follow that advice, not only will the states find less fraud, they will also lose a large increase in the federal share of Medicaid False Claims Act settlements, due to language in the Deficit Reduction Act that says an increased share is contingent on a state having a law as strong as the federal statute,” he continues. “For some states, that can work out to be a loss of as much as one-third of the total they might otherwise collect.”

UPDATE: The Illinois General Assembly approved changes to state whistleblower protections. The amendments to the Illinois’ Whistleblower Reward and Protection Act in House Bill 5951 cleared last week and was sent to Governor Pat Quinn (here’s the bill).

It’s been a very busy week around here, but what I do have time to do is take a look at the recent infusion of capital the company has experienced. An investment group called Seaside 88 has announced their intention to buy a large amount of Generex stock. Among the Generex investors calling for my head (and other parts of my anatomy), opinion seems divided about Seaside 88 and my relationship to them (which, let me state right up front, is completely nonexistent – I’d never heard of the outfit until this stuff came up). Some of the hardy GNBT folks point to this deal as evidence that I’m a fool, because here’s this big investment outfit pouring money into this wonderful company and its promising product. Others seem to think that I’m being paid off by said big investment outfit, that I’m a black-hatted stock-basher out to secure Seaside 88 a better deal as it scoops up this wonderful stock on the cheap.

Which exciting story to believe? Not for the first time, I’m reminded that too many people who invest in small “story” stocks have worldviews that resemble the story lines of profession wrestling. I’d call it Manichean, but that’s a bit too elevated. No, it’s all Good Guys and Bad Guys, and there’s no room for someone like me, a person with no money in the game who finds the whole thing bizarre and amusing. The smaller the stock prices involved, by the way, the crazier the investors seem to be.

So, Seaside 88. If you go do an EDGAR search on them, you find that they’ve done similar stock-purchase deals with a number of small companies (and other deals show up as you Google for press releases). Flywheel energy storage companies, obscure fuel-cell makers – it’s quite a collection. My personal favorite is Ensurge, Inc., and if you’d like to know what business they’re in, you’ll just have to read the language in their 10-K. If you’re not snorting in derision by the time you get to the South-American-gold-mining stuff, then you’re a born penny-stock investor. You’d have to use threats of bodily harm to make these things a centerpiece of my own investment strategy – but hey, that’s why I’m going to finish up eating off-label cat food in a trailer while the Generex shareholders are sailing their yachts through the Greek islands. These things have a way of evening out.

So, who are these Seaside 88 people, anyway? Well, as is often the case, there’s a whole little constellation of related companies. There’s your Seaside Analytics, your Seaside Capital Management, your Seaside Capital II, and so on. One person who figures prominently in all of them is William Ritger, who’s been in the investment business for some years now. Here’s a biography of him from one of the companies he’s helped to found.

In fact, he’s been in the business long enough for this article from the the New York Times to turn up. It refers to a former venture of his, Research Works, which seems to have issued favorable reports on obscure stocks – causing their prices to jump – but without making much of the fact that he was being paid by the companies involved to write those reports. One hopes that he is no longer in the business of promoting small stocks in this manner.

Another name that shows up when you search the Seaside family of investment partnerships is Denis O’Donnell. Looking over the EDGAR filings featuring his name, you find his ongoing relationship with a company called American Bio Medica, which I note has also been listed as one of the house favorites of a micro-cap “pump and dump” junk-fax operation. He’s also been involved with Columbia Laboratories – now of New Jersey, but formerly of Hollywood, Florida, where (interestingly enough) they were mentioned in that same New York Times article as the subject of one of those paid-for investment reports back in the 1990s. One hopes that he is keeping better company now.

So, Generex investors, enjoy your stock, and enjoy the company of the others who have seen fit to invest in it. I will not be putting any of my own money into it, and they won’t let a person short companies that trade at 60 cents a share. Which is too bad, in a way, because the great majority of such companies go to zero.

Frankly I don’t care when and if the FDA issues guidelines around social media. It isn’t going to make one bit of difference for patients or consumers because in order to have a relationship you have to trust the person your engaging with and consumers don’t trust the drug industry or the FDA.

Just a little while ago the FDA sent a letter to a drug company because they dared to simply the language on their website in a way that makes medical information easier to understand. Forget the fact that most people don’t understand complicated language on product websites the FDA is doing what is best for them not consumers. If there is any doubt get someone who is not in our industry to try and navigate the FDA website.

Consumers & patients are turning to Internet for health in bigger numbers and that is probably going to show substantial increases in the years to come. Not only is there a lack of trust in what the drug industry and the FDA is telling us they also don’t have the time to really talk to their physicians about treatment options or medications. For right now it seems the best course of action for most patients is to get as much information as they can via the Internet so they can make informed and educated health decisions.

As for healthcare legislation I keep hearing how the “American people don’t want healthcare legislation” but these people are only one catastrophic illness away from learning how much power health insurers have and how little they have. We face an uncertain future in healthcare and as more Boomers age they could indeed find out that as they need more healthcare their savings is going to be siphoned off to pay outstanding balances to physicians and medical facilities.

With everything that is going on I would like to know who is here to speak for consumers and patients? It surely isn’t the FDA who continues to get most of their information from agency people who have a vested interest in seeing new guidelines passed. Consumers don’t really care what the FDA does or says, for them the best way to look out for their interest it to look out for number one and the best way to do that is to go online.

If your a patient who is taking either Advair or Symbicort you’re probably either very confused this morning and wondering what the hell you should do next. The FDA wants you to stop taking these medications and talk to your doctor about your asthma treatments. But the key question that a lot of people are probably asking is “why in the hell were these drugs approved in the first place?”

There is nothing worse than taking your Rx as prescribed for a long period of time only to learn that everything you were told about the drug is probably not relevant anymore. With close to 30% of patients non-compliant new warnings like these could add to more people questioning the use of their prescription drugs. It would be interesting to see just how many people are non-compliant because they are afraid of taking prescription medications because of potential side effects.

Welcome to the new FDA. An FDA that is making life for patients more difficult. An FDA whose website is about as user friendly as a maze of barbed wire. Those who can navigate the FDA’s website often find the language difficult to read and understand and leave with more questions than they originally had. The FDA is out of touch with what the American public needs and wants in health information; clear, concise, easy to understand information on the drugs they take everyday. No wonder the America public is skeptical of newly approved drugs ? They don’t want to take these drugs and find out 2-4 years later that the drugs are more dangerous than they originally thought.

Welcome to the FDA

The Astelin (azelastine HCl nasal spray) letter, citing a waiting room sign for the allergy drug, DDMAC objects that “in contrast to the consumer-friendly claims on the sign, some of the risk information that is disclosed (i.e., ‘somnolence’ and ‘rhinitis’) is presented in medical terminology that is not likely to be understood by consumers.”

Similarly, the citation of a patient brochure for OraVerse states that: “While the patient brochure presents efficacy claims for OraVerse in language that is easily understandable to consumers, it presents risk information using complex medical terminology that is not likely to be comprehended by the same audience.”

Both citations rely on the prominence standard: FDA considers ads to be misleading “if they fail to present information about the risks associated with a drug with a prominence and readability reasonably comparable with the presentation of information relating to the effectiveness of the drug.”

What does this mean for the drug industry and patients? It means that they are likely to continue to be confused by the language that the FDA wants and it means that the drug industry may not be able to engage and talk to consumers & patients via social media without using the label as the script.

While there is a fine line between omission of information and user friendly language this is another clue that the FDA is not willing to make it easier for consumers and patients to understand medical information even though more of them are searching for medical information than ever before. In fact our recent research clearly showed that consumers were frustrated with the language on drug product sites.

Something else to consider;

▪ 46 million American adults are functionally illiterate.

▪ 40 million Americans read at or below 4th grade reading level.

▪ Nearly half of all American adults –90 million people– have difficulty understanding and using health information.

▪ The average American comprehends between a 4th – 7th grade level.

▪ 26% of Americans can’t understand when their next doc appt is scheduled.

▪ 42% of Americans do not comprehend instructions to “take medication on an empty stomach.”

▪ 49% of Americans cannot determine if they are eligible for free care by reading hospital financial aid forms.

▪ 60% of Americans cannot understand a standard consent form.

Leave it to the FDA to think like scientists and enforcers rather than consumers and patients.

“As consumers utilize a wide variety of sources to learn about prescription medications, it may not be optimal for the FDA to require that pharmaceutical companies include the same details in each of the channels they use to communicate information about their prescription drug products,” said Morris S. Whitcup, Ph. D., chief research officer at ORC Guideline. “When we asked consumers specifically about their preferences for obtaining prescription drug risk information online, we learned that many would appreciate a truly condensed version of such disclosures, accompanied by links to obtain more detailed information.”

The study found that the top ways consumers prefer to see prescription-drug risk disclosures presented online are:

◆ Direct links to an independent website such as WebMD (32%).

◆ Having a condensed version of risk disclosures available one click away (27%).

◆ A direct link to a pharmaceutical company that provides the information (26%).

◆ A direct link to a government website that provides the information (25%).

According to the ORC report;

The survey also indicated that roughly half (55 percent) of respondents considered pharmacists and doctors to be a sufficient source for information about their prescriptions, while another 35 percent did not feel that the printed information supplied by the pharmacy about their prescription was important. Among those who did read drug information supplied by their pharmacy or the drug manufacturer, those that found it hardest to understand fell in the 45-54 age bracket (23%), followed closely by the 55-64 age bracket (22%). “With nearly a quarter of respondents in each of these age brackets indicating they may have a hard time understanding supplied drug information, and with a number of people not bothering to read it at all, there is clearly a need for better dialog between patients, particularly in the middle-aged to senior age groups, and their doctors and pharmacists, to ensure the safety of consumers,”

Those of you who have been readers of posts on this website know that I have been saying that label and warning language is hard to read and confusing at best. Pfizer gets kudos for trying to simply the warning of Rx drugs but the language is still often difficult to understand.

WHAT DOES THIS ALL MEAN ?

It means that consumers/patients will continue to seek out others experiences via social media because they don’t understand fair balance and want to know what others experienced while using the medication. Once again the FDA has dropped the ball here. They have failed to be responsive to the wants and needs of the public and to give the public the information they want in a form they can understand. Drug companies have also failed to be proactive in this area and most just do what the FDA wants them to do.

The study found that the top ways consumers prefer to see prescription-drug risk disclosures presented online are:

◆ Direct links to an independent website such as WebMD (32%).

◆ Having a condensed version of risk disclosures available one click away (27%).

◆ A direct link to a pharmaceutical company that provides the information (26%).

◆ A direct link to a government website that provides the information (25%).

According to the ORC report;

The survey also indicated that roughly half (55 percent) of respondents considered pharmacists and doctors to be a sufficient source for information about their prescriptions, while another 35 percent did not feel that the printed information supplied by the pharmacy about their prescription was important. Among those who did read drug information supplied by their pharmacy or the drug manufacturer, those that found it hardest to understand fell in the 45-54 age bracket (23%), followed closely by the 55-64 age bracket (22%). “With nearly a quarter of respondents in each of these age brackets indicating they may have a hard time understanding supplied drug information, and with a number of people not bothering to read it at all, there is clearly a need for better dialog between patients, particularly in the middle-aged to senior age groups, and their doctors and pharmacists, to ensure the safety of consumers,”

Those of you who have been readers of posts on this website know that I have been saying that label and warning language is hard to read and confusing at best. Pfizer gets kudos for trying to simply the warning of Rx drugs but the language is still often difficult to understand.

WHAT DOES THIS ALL MEAN ?

It means that consumers/patients will continue to seek out others experiences via social media because they don’t understand fair balance and want to know what others experienced while using the medication. Once again the FDA has dropped the ball here. They have failed to be responsive to the wants and needs of the public and to give the public the information they want in a form they can understand. Drug companies have also failed to be proactive in this area and most just do what the FDA wants them to do.

The objective of this research was to learn both how patients search for health information on the Internet and how they determine which information is actionable towards requesting a specific healthcare treatment. Some of the preliminary findings:

-Patients search for health information is driven by specific triggers with those triggers being symptoms of a health problem, information in preparation for a physicians office visit, after a diagnosis. Interesting to note that women are more proactive where men are not.

-Consumers are overwhelmed at the amount of health information on the Internet and therefore depend on branded health portals (Web MD) for health information.

-Key choice of where they go for health information:credibility.

-Although they will use social media for health information credibility is largely dependent on who sponsors the social media page(s). Patients are most interested in others experiences with specific healthcare treatments including specific medications. However, for more serious conditions they wanted information from others on “how to live with the disease”.

Physician Research

How customized patient ed might work (click to enlarge)

We developed a story board (see enclosed) and presented the idea to PCP’s for their input and feedback. Here are some preliminary results;

-Physicians thought this was a great idea but it has to be easy to implement as they do not have the technical expertise in house to update the CMS or implement.

-Cost is a definite issue and some recommended that this be a turn key Internet based system

-”Anything that improves patient outcomes and gets them back in my office for a follow up visit is a winner”

-The information contained in the CMS should not be overly promotional and the language should be easy for patients to understand.

-They should have the option to print in the office but it should be packaged professionally to hand to the patient as they leave.

Like I said this is only preliminary findings but I am really excited because there are some great ways to make a difference in patients lives and in the end isn’t that what it’s all about ?

The goal of this research was to determine how physicians felt about medical information on health website. While I heard that they were supportive they also voiced concerns about misinformation and online tools that patients often use for self-diagnosis. This was especially true since various media sources indicate that visits to physicians offices seem to be down as the result of the recession.

As an example a physician was taken back when a patient came in saying that he had high cholesterol because he took a home cholesterol test. Since these tests only tell you your total cholesterol, they do not distinguish between good and bad cholesterol, the doctor said he has to spend some time with his patient explaining why he needed another blood test. The moderator at this point asked the doctor if he thought that this “test” was coming between him and his patient to which he respond “yes it is”. “It’s OK to use a home test but a diagnosis of high cholesterol and treatment recommendations are what we make together not the patient alone”.

When it came to health and pharma product Websites we heard an earful: “There are just too many sites for patients now and they’re getting more and more confused by all the information out there”. We probed on pharma product websites and heard that most feel that ; “they are overly promotional and don’t provide enough balance of information on disease conditions”. Another said “the language is often difficult to understand and patients come in with highlighted words they printed from the Website and ask me what they mean”. “I don’t have time to interpret websites, they have to make it easier to understand and for God’s sake stop with the self diagnosis tools”, said another.

Most physicians in the research said that they are seeing more patients come in with information printed off the Internet but that some of the information is “downright scary”. We had a lot more insights and in the four cities that we conducted research in the PCP’s were not afraid to voice their opinions on the changing face of healthcare in this country.

At the end of the 4 sessions we asked them what we could do to make it easier for them and we heard the following suggestions:

1. Make the content easier to understand for patients and anticipate issues and questions.

2. Make sure that there is information of the disease state along with highlighting the impact of lifestyle changes on reversing some health conditions like diabetes or high cholesterol.

3. Stop with so many diagnosis tools, they are being used by too many patients to self diagnose. Above all do not come between “me and my patients”. Also ensure that communication to patients includes the need for follow up visits.

4. Give me online content to use on my practice website.

This research gave us a lot of insights and we even had some physicians list the good (Enbrel.com) and bad websites (too many to mention). They are afraid of patients self diagnosing and not going to their doctors. “Preventative care is important and we want patients in the office before a health crisis is imminent”. “Anything that can help get patients in my office would be welcome”.

It didn’t take long for Aleve to start running commercials that target the latest news on Acetaminophen or Tylenol. TV spots are running showing that “two Aleve can last all day compared to a lot of Tylenol”. Not to be outdone the makers of Tylenol are running spots saying that Acetaminophen is the most recommended pain reliever by doctors with a lot of safety studies behind them. If you’re a consumer you just want a good pain reliever and you don’t want to have to spend time online determining what is best for your headache or aching legs. The FDA is confusing the hell out of consumers and is doing little to truly explain risks.

Last week I posted Part 2 of the examination of the past two quarters for FDA DDMAC letters.  The week before that, I posted Part 1.  Finally, I am done with Part 3, examining the last quarter of 2008 and mining out the takeaway lessons.  Next quarter I promise to be more timely!  The quarter included violative DTC ads, web pages, patient brochures, flashcards and direct mail pieces.  There were a few important lessons from what was sent out by FDA.