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The New York Times that W. Scott Harkonen, MD the former chief executive of InterMune, a Brisbane, CA biopharmaceutical company, was convicted yesterday for issuing what federal prosecutors called a misleading press release that contributed to off-label sales of the company’s drug Actimmune.

Actimmune is bioengineered form of interferon gamma approved in 2000 to treat children and adults with chronic granulomatous disease (CGD) and severe, malignant osteopetrosis—two relatively rare genetic diseases. But the main sales of the drug, which peaked at $141million in 2003, came from an unapproved use: treating idiopathic pulmonary fibrosis, a scarring of the lungs that can be fatal. While licensed physicians in the US can prescribe approved drugs for off label, it is illegal for drug makers to promote the use of prescription drugs to treat indications for which the drug didn’t receive approval.

According to the Times article, InterMune conducted a large clinical trial testing Actimmune as a treatment for the lung disease. The drug did not achieve the clinical endpoints of the trial, which was to improve lung function of patients receiving Actimmune as compared with patients receiving a placebo. However, a review of the statistical analyses of the trial revealed that if only the patients in the trial with mild or moderate disease were considered, those who got the drug lived longer than those who received the placebo .The company highlighted the “survival benefit” of patients treated with Actimmune in a news release, issued in August 2002.  Following the press release, sales of Actimmune (which costs about $50,000 per year) peak at $141 million in 2003—the drug was mainly being used to treat idiopathic pulmonary fibrosis an indication for which the drug hadn’t received regulatory approval. Because of this, federal prosecutors contended that the news release was part of a scheme to induce off-label sales of Actimmune. Interestingly, in 2007, a second large clinical trial of Actimmune found that the drug didn’t prolong the lives of patients with pulmonary fibrosis.

The InterMune case isn’t unique in the life sciences industry. Time and time again companies are charged with off-label promotional activities and typically these cases are settled before they go to trial. To that end, the InterMune case is an exception but Harkonen’s conviction sends a warn drug company executives that the US government takes off label promotion seriously and it will no longer be tolerated.

While it can be argued that off label drug use can benefit patients and ought to be allowed, off label promotion of previously approved drugs allows drug companies to benefit financially without investing in expensive clinical trials to win regulatory approval for the off label indication. In other words, off label promotion of prescription drugs can be a financial windfall for companies and induce them to place profits ahead of patient safety and drug efficacy. This is why promotion of off label use of prescription drugs is illegal and a prosecutable crime. 

It is important to remember that prescription drugs are required to undergo a rigorous regulatory review to insure that they are safe and efficacious. While the use of approved drugs to treat off label indications may benefit some patients, the drugs in question must be rigorously tested for safety and efficacy to treat the indication before they are used to in large numbers of patients. And, as we have seen in recent years, even drugs that have gone through clinical testing and garnered regulatory approval may not be as effective or safe when used to treat billions of patients!

Until next time...

Good Luck and Good Job Hunting!!!!!!!

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Pharmaceutical,biotechnology and other companies that sell prescription drugs and devices are deathly afraid of adverse events (AEs) associated with their products. For those of you who may not know, companies with approved prescription drugs and medical devices are required to track and report any adverse events associated with their products to regulatory agencies like the US Food and Drug Administration (FDA). If FDA receives enough AE complaints about a product, the agency will investigate to determine whether or not there may be efficacy, safety or tolerability issues with it. And, if FDA thinks that the AEs are legitimate, it may ask a company to conduct Phase IV clinical trials with the product in question or require that changes be made to the product’s label. Not surprisingly, these outcomes can be time consuming and perhaps more importantly, costly. Label changes—especially for blockbuster products—frequently lead to changes in physician prescribing habits which can translate into a loss of revenue. Despite the fact that ALL drugs exhibit AEs, many companies falsely cling to the hope that there will be few, if any, AEs reported for their products.

While drug makers are very familiar with the range of possible AEs associated with their drugs—all AEs for a drug are identified and reported during clinical trials—pharmaceutical executives are concerned about social media activities, because they fear that than the number and frequency of AEs reported for their products will increase. This, in turn, would prompt FDA and other regulatory agencies to investigate and more closely scrutinize their marketed products. As Jonathan Richman, author of the Dose of Digital Blog points out in an excellent post entitled the “Myth of Adverse Event Reporting” AEs are a fact of life for prescription drugs. And, that social media may help to improve adverse reporting. Like Jonathan, I contend that social media might allow drug makers to more effectively identify potential safety issues with a product earlier in its lifecycle and thereby minimize possible deleterious effects of the drug on certain patient populations. I think that drug manufacturers ought to begin to consider how they might effectively use social media to improve AE reporting rather than ignore the potential upside of this new medium.

The Myth of Adverse Event Reporting

Adverse Events are nothing more than negative reviews. If you want people to genuinely talk about your brand, they are going to say negative things. But how often do posts include adverse events? Nielsen decided to take a look at this rather than simply assume it was ” a lot,” which of course is a difficult number to manage. Nielsen looked at Yahoo Health boards and took 500 postings. Of these, only 1 contained enough information to qualify as an adverse event that needed to be reported. That’s 0.2%. Why so low? Turns out that someone simply saying that your drug caused them to have a headache isn’t enough to qualify as an adverse event. Nielsen summed up the pieces of information required to report an adverse event and there are four pieces: “(i) an identifiable patient; (ii) an identifiable reporter; (iii) a specific drug or biologic involved in the event; and (iv) an adverse event or fatal outcome.” (Hat tip to Pharma 2.0 for the summary). The study showed that one or two of these pieces were often available, but not all four. In addition, they found that it would be impossible to get all four even with some effort. In fact, the FDA says, “[Without these pieces] a report on the incident should not be submitted to the FDA because reports without such information make interpretation of their significance difficult, at best, and impossible, in most instances.”

This is because people often don’t register or leave their personal information in a post, so there is no way for a company to follow up and fill in the blanks. Naturally, if there is something significant, every effort should be made, but on the often anonymous Internet, this is usually difficult. Suppose for a moment there were several adverse events that need to be reported. How often do they need to be reported? The FDA is pretty clear on this. For new drugs, reports need to be filed quarterly for three years. After that, it’s annually. For “serious and unexpected” events, these have to be reported within 15 days. However, there’s a pretty high threshold for an adverse event to be considered “serious and unexpected.” Every company already has these reporting channels in place, so it is simply a matter of including adverse events received from social media into the workstream. 

Yes, it’s a balance. The fact is adverse events should not be the reason why healthcare shies away from social media. These risks can easily be mitigated and, if done right, can actually be used in a positive way. So, don’t use adverse events as an excuse anymore. You’ve got the data. 1 in 500 posts include a reportable event. You report quarterly at most (which you’re doing anyway). How much ongoing effort do your other marketing programs require? Probably quite a bit more than this. Next time you hear this excuse, you’ve got the data to dispel the myth of adverse event reporting.

Until next time...

Good Luck and Good Job Hunting!!!!!!

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One day after the US Food and Drug Administration (FDA) approved Dysport, a new product that will compete with Botox, the agency ordered that labels for all botulinal toxin-based drugs must carry a black box safety warning. For those of you who may not know, that is the most stringent kind of safety warning label—viewed by many in the industry as “the kiss of death”— that the agency can order to appear on the products that it regulates. 

Black boxes (literally a black box with bold-face risk information) are typically reserved for medications that are know to have serious or life-threatening side effects or risks. For example, many antidepressants—most recently serotonin re uptake inhibitors (SRIs)—carry black box warnings of increased danger of suicidal thoughts and actions. 

Over the last 20 years FDA approved Botox to treat crossed eyes, eyelid spasm, severe underarm sweating and cervical dystonia (a painful and severe neck condition that can cause an abnormal head position) Cosmetic Botox was approved to treat skin folds and wrinkles in 2002. Allergan, the company that manufactures Botox, reported $1.3 billion in worldwide sales of the drug in 2008. 

Botox and Dysport are injectible products made from the highly paralytic toxins produced by the bacterium Clostridium botulinum. Botulinal toxins interfere with muscle contractions and patients with botulism food poisoning exhibit what is known as “flaccid paralysis.” Afflicted individuals cannot breather and will die without early intervention. FDA order the black box safety warning labels because there were numerous reports of serious health problems, complications and deaths caused by the drug spreading from the site of injection to other parts of the body. 

Most of the problems with Botox resulted from the overuse of Botox for unapproved treatments like limb spasticity in children with cerebral palsy (although misuse of the product for cosmetic purposes may have also contributed to the problems). The agency will now require that all botulism-based products carry a black box warning explaining that the medication has the potential to spread from the site of injection to other body sites—with the potential to cause serious problems like difficulties swallowing or breathing. Also, it will require manufacturers of botulinal products [Allergan (Botox) and Ipsen/Medicis Pharmaceuticals (Dysport)] to send physicians letters warning of the risks and to craft medical guides given to patients at the time of injection. 

The new warning labels will likely do little to discourage the rampant use of Botox and Dysport for cosmetic indications. After all, beauty will always come before safety! 

Until next time... 

Good Luck and Good Job Hunting (looking younger may help)

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The Bush administration spent the last eight years trying to weaken and dismantle the US Food and Drug Administration (FDA).  I thought the carnage at the agency would end in the waning days of one of America’s worst leaders. Sadly, I was mistaken.

As many of you may know, FDA regulations forbid drug companies from promoting off label use of previously approved drugs. Not surprisingly, drug companies were able to find loop holes in the regulations and off-label drug promotion reached unprecedented levels in the early 2000s. In response, the agency embarked on an aggressive, unrelenting campaign to combat off label drug promotion by drug manufacturers. This effectively changed the way in which pharmaceutical sales representatives interacted with physicians in the past few years. No longer would there be unsolicited gifts, lavish pizza lunches for office personnel or tickets to local sporting events. Neither the drug makers nor physicians were happy about the rule changes but the revised guidelines helped to lessen off label promotion of previously approved drugs. That said, it came as something of shock late last year, when FDA officials proposed a new set of guidelines that would ease the restrictions on off label drug promotion.

The new rules would allow drug makers to supply physicians with copies of published research reports describing off label uses of drugs that were previously approved for other therapeutic indication. As you might have guessed, the drug companies are ecstatic with the new guidelines. Who needs pens, mugs or pizza when you can simply hand a physician a reprint of article that show that off label use of an approved drug can treat potentially life threatening medical conditions.  What an ingenious way to boost sales of extant drugs for new indications without having to spend larges of money trying to win regulatory approval for them. While this would be a financial boon to the pharmaceutical industry, I don’t think it would be in the best interest of patients who may be prescribed a drug that hasn’t undergone the rigorous scrutiny of controlled, human clinical trials.

Many congressional democrats and drug industry critics opposed the guidelines when they were first proposed last year. But, like many other times over the past eight years, the Bush administration prevailed. Today, the agency announced (with little fanfare) that the new off label drug use guidelines would go into effect—one week before Barack Obama is inaugurated as President. 

Until next time…

Good Luck and Good Job Hunting!!!!!!!!!

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After beating Wall Street expectations and disclosing positive results from an osteoporosis (densomab) clinical trial, Amgen was ordered by the US Food and Drug Administration (FDA) yesterday to change the labels for its EPO drugs (Epogen and Aranesp) that will likely further restrict their use in treating patients with cancer.

The label changes ordered by FDA represent the first time that the agency has invoked its power to change prescribing information for drugs that it previously approved. In the past, FDA could only negotiate with drug manufacturers about changes to labels and prescribing information. In my opinion, it’s about time that FDA has been empowered to unilaterally order these types of changes. I have long contended that negotiations between the agency and drug makers about labeling and prescribing information is not in the best interests of Americans who use prescription drugs. To that end, it was negotiations between FDA and Merck about whether the serious cardiovascular risks associated Vioxx should appear on the Vioxx label (they didn’t) that lead to the misuse, safety problems and ultimate recall of the drug.

While the ordered label changes are not good news for Amgen and its partner Johnson and Johnson which sells Procrit (EPO manufactured by Amgen and sold by J&J), they are in the best interests of all Americans who use these drugs to treat anemia caused by cancer chemotherapy and kidney disease.

Until next time….

Good Luck and Good Job Hunting (avoid A Thousand Oaks, CA)!!!!!!!!!!

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By law, drug makers are prohibited from marketing or promoting (in any way) their medicines for uses that have not been approved by FDA. But, somewhat paradoxically, physicians who are licensed to practice in the US can prescribe drugs for uses beyond FDA-approved indications, a practice known as off-label use. The agency is no stranger to the issue of off-label drug use and has vigilantly policed the industry over the last decade to prevent the practice. Drug makers including Pfizer, Astra Zeneca, Eli Lilly, Amgen and others have been targeted by federal prosecutors for off-label marketing practices. Click here to see which types of drug are commonly prescribed for off-label use.

However, in something of a policy reversal, FDA officials proposed last Friday new guidelines that would allow pharmaceutical companies to use peer-reviewed medical journal articles to promote drugs for unapproved uses. The proposed guidelines will replace a law that expired in 2006 law. Under the expired law, companies had to submit copies of the articles to FDA for review before sending them to physicians. Under the new proposal, drug companies don’t have to submit articles to the FDA before distributing them to physicians. The agency says it will not punish companies for distributing literature on off-label use if they adhere to certain practices. Articles should not be false or misleading and should come from a peer-reviewed journal that is not influenced by a company. The proposal also says companies should attach a disclaimer to the materials indicating FDA has not reviewed them.

I, along with Congressional Democrats, most notably Henry Waxman (D-CA), am totally baffled by the proposed new guidelines.According to Mr. Waxman, the new guidelines would create a “large loophole” in laws against off-label promotion. “It’s a conflict of interest for the company to be promoting sales when they haven’t been able to establish that a drug is safe and effective through the rigorous FDA process,” he said. Not to mention that a company could save hundreds of millions of dollars by not conducting clinical trials to gain approval for an off-label indication. Risperdal, a Johnson and Johnson medication that is approved to treat serious mental disorders like schizophrenia, bipolar disorder and irritability associated with autism was used off label 66% of the time and brought in $4.2 billion in 2006. If you were the CEO of J & J would you spend any additional monies to win approval for new indications for Risperdal?

I would think that by now the agency would have figured out that drug manufacturer are incapable of policing themselves; there is simply too much money at stake. And, unfortunately, profits will always come before patient safety.  In my opinion, the proposed guidelines are another egregious example of just how much influence the pharmaceutical and biotechnology industries have at FDA. The Bush administration has done everything in its power to destabilize and emasculate the agency. The American public no longer has confidence in FDA and the products that it approves. Something has got to change to restore a sense of wellness in America!

Until next time…

Good Luck and Good Job Hunting!!!!!

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Still reeling from lawsuits filed last week by ex-sales reps’ alleging improper marking of Enbrel to treat patients with psoriasis, Amgen was subpoenaed on Monday by New Jersey's attorney general regarding allegations that the company promoted Enbrel for unapproved uses.

In the subpoena served Monday, Attorney General Anne Milgram is seeking "a comprehensive array of documents and information" concerning the marketing and sale of Enbrel from July 2002 to the present.

The subpoena calls for Amgen to deliver the required materials by Feb. 4.

Although doctors are free to prescribe medicines as they see fit, drug companies are only allowed to promote their products for uses that have been approved by the U.S. Food and Drug Administration and appear on product labels.

Until next time…

Good Luck and Good Job Hunting!!!!!!!!

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