Roche Wants to Buy Genentech

At lunch the other day, I was telling a bunch of people about how brilliant Roche’s biotechnology strategy has been for the past 20 years or so. All of this changed for me on Monday, when Roche announced that it wanted to buy the remaining shares of Genentech that it already doesn’t own for $ 43.7 billion —Roche currently owns 56% of Genentech’s stock. More importantly, Roche doesn’t have control of Genentech’s board of directors nor does it influence corporate strategy or product development.

Unlike many other pharma companies who have historically purchased  biotechnology companies and then integrated them into existing corporate structures, Roche previously opted to buy controlling interests in companies and then allowed them to continue to operate independently with little corporate input or guidance. Unlike pharma culture, which is very structured and inherently conservative, the most successful biotechnology companies have been built on cultures that promote creativity and “thinking outside the box”.   If Roche buys Genentech and attempts to integrate it into the existing Roche family of companies, I suspect that all of this will change dramatically.

For the past 30 years or so, Genentech has been one of the brightest stars in the biotechnology universe.  Genentech’s management team worked long and hard to implement and maintain a vision that was formulated way back in the late 1970s when the company was first formed. Even though it is the world’s largest and most financially successful biotechnology company, Genentech has steadfastly resisted the temptation to go “corporate” and has worked diligently to maintain its “biotechnology identity” —symbolized by innovation, creativity and employee-centric policies.

I have no doubt that if the Roche-Genentech deal is approved, there will be a mass exodus of talent from the company. Based on my experience, a publicly-treaded biotechnology employee’s greatest fear is the dreaded corporate takeover! I have yet to meet a biotechnology company employee who is willing to sacrifice freedom and creativity (despite a possible financial upside) for more structure, discipline and an endless plethora of rules! 

In my opinion, the deal makes sense for Roche—competition in the cancer space is intense and they want to hedge their future success on Genentech’s oncology franchise. In the best case scenario, Roche will buy Genentech but allow it to operate as a wholly owned subsidiary with an independent management team that spends as little time in Basel as possible. I think the old adage “If it ain’t broke, don’t fix it” is particularly apt here!

Until next time….

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

Congrats to INSMED...I Think!

Richmond Va-based INSMED, a US-based follow-on biologics manufacturer, posted a press release on its website entitled: “Insmed Announces First Human Bioequivalence Data for a Follow-on Biologic by a U.S. Company” that reports on the results from a Phase I clinical trial that demonstrated that it lead product INS-19 was bioequivalent to Amgen’s Neupogen(R) (recombinant G-CSF) in stimulating human white blood cell production. 

, Dr. Geoffrey Allan, President and CEO of Insmed said  "These results are very exciting, as they represent Insmed's ability to replicate a protein product, to bring that product rapidly through the clinic and to demonstrate clear bioequivalence to the innovator drug," said "To our knowledge, we are the first U.S. company to report human bioequivalence data for a follow-on biologic product, validating the idea that follow-on biologics can be a scientific reality in the U.S. and that Insmed is well positioned to be a leader in the field. “ The company has requested a meeting with FDA to discuss the design of a Phase III human clinical trial for INS-19.

I am not sure why INSMED is so excited about its results. Sandoz essentially accomplished the same feat with Omnitrope, its biosimilar version of recombinant human growth hormone (HGH)and it took a law suit and a loophole in the approval process for growth hormones for FDA to allow it to be sold in the US. In my opinion, until legislation is passed that provides a clearly defined legal pathway for approval of follow-on biologics I suspect that INS-19 will suffer the same fate (or perhaps worse) than Omnitrope. Bioequivalence is only legal defined for and relevant for approval of small molecule NOT BIOLOGICS when seeking expedited approval for generic versions of branded products. That said, I want to tip my hat to INSMED for its willingness to take a lead role in the fight to get follow-on biologics approved in the US. Finally, there is nothing like an edgy press release and a few bloggers to bring an issue that is rapidly losing momentum back to the forefront.

Kudos to INSMED!!!!!!

Until next time….

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

Is There Another Storm Brewing at Merck?

The old adage “When it rains, it pours” is particular apt for the bad news that has plagued the once venerable Merck & Co for the past five years. First, there was the Vioxx scandal, followed in short order by the Vytorin and Singulair messes and now it appears that the company’s new anti-cervical cancer vaccine, Gardasil, may have —pardon the expression — a few “warts” on it. 

Last night on my local nightly news, there was a brief report about emerging safety issues with Gardasil. According to the report, adverse events ranging from “massive wart outbreaks to seizures and paralysis” have been reported for the anti-HPV vaccine. Since its approval in 2006, over 8,000 adverse event reports (the total number of people vaccinated was not disclosed) and 18 alleged deaths have been reported for Gardasil (although none of the deaths has been directly linked to Gardasil vaccination). This news comes on the heels of a recent Wall Street analyst’s report indicating that sales of Gardasil are much lower than expected. It appears that the vaccine, once considered by Merck insiders as the new blockbuster that could save the flagging drug maker, may, after all, be relegated to specialty drug status.

As many of you may know, GlaxoSmithKline (GSK) is seeking US approval for its anti-cervical cancer vaccine called Cervarix. Although Merck beat GSK to market, Cervarix has undergone more clinical testing and allegedly may have a better safety and tolerability profile than Gardasil (only the regulatory agencies know for sure). Nevertheless, it is not clear whether GSK will benefit or be injured by the negative publicity that Gardasil is receiving. As I mentioned in a previous post, the US Food and Drug Administration (FDA) recently delayed Cervarix’s approval pending submission of additional data that the agency requested from GSK.

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VEGF Inhibitors: Real or Imagined Cancer Treatments?

Monoclonal antibodies (MAbs) directed against vascular endothelial growth factor (VEGF) receptors on cancer cells, have been found to slow the growth of a variety of cancers including colorectal, breast and lung.  While a number of blockbuster biotechnology products( based on these MAbs (Avastin by Genentech/Roche and Eribitux by Bristol-Myers Squibb/ImClone/Merck KGA) have been approved to treat a variety of different cancers their effectiveness as cancer treatments has been the subject of intense debate since their approvals.

Although numerous human clinical trials have shown that VEGF inhibitors slow the growth and development of tumors, they, as a class, don’t seem to significantly increase the survival time for most cancer patients. Further, Avastin and Erbitux are generally not used as stand alone treatments but are used in combination with more tradition anti-cancer chemotherapies. The high costs of these drugs, (Avastin’s worldwide sales hit $ 3.5 billion last year) and their variable effectiveness have caused many to question the usefulness of this class of drugs to treat cancer patients.

The well-publicized use of these drugs as cancer treatments coupled with anecdotal evidence about their effectiveness has put practicing oncologists between a rock and a hard place when it comes to treating patietns with cancer. In an article in Sunday’s New York Times one prominent oncologist said that depsite the controversy,  “I still use Avastin routinely. It’s not a slam dunk and, in fact, the incremental benefit may be more modest than we want to admit.” Others are more sanguine about VEGF inhibitors as cancer treatments “Even when these drugs ‘work,’ what kind of impact are you talking about?” said Fran Visco, president of the National Breast Cancer Coalition. But we market them and give them to everybody.”  

Nevertheless, most oncologists find it difficult to withhold Avastin or Erbitux from cancer patients seeking hope. As one oncologist put it “ When I am not sitting in front of a patient, I think about whether drugs like Avastin are worth it to society. But when facing a seriously ill patient, who, based on clinical trial results, might benefit — even if only a little — from Avastin, I think about the patient’s needs.” 

Regardless of their therapeutic value, the main issue with this class of anti-cancer drugs is cost. Avastin treatment costs patients about $4000-$9000 per month— Eribitux treatment is even more costly! While Medicare and most private insurers cover 80% of the cost, patients can be responsible for 20% or more of treatmetn costs.  As posited in the Times article “If Avastin were inexpensive or if it cured cancer or even held it at bay, as the drug Gleevec does for blood cancer, few might care.”

Are anti-VEGF drugs real cancer treatments or expensive red herrings? Clearly, the jury is still out on that one. That said, I think that only cancer patients can truly provide an accurate response to that question!

Until next time…

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

Life Sciences Patent Factoid

According to a survey of 1,800 American professors in the life sciences conducted by economists at the University of Wisconsin-Madison, 90% of life sicentiest hold only one or no patents.  This means that  remaining 10% hold more than one (and are probably weathier than the other guys). 

The results of the study led its authors to surmise that despite the recent explosion in patenting in the life sciences, a majority of academics still do research the "old-fashioned way"--by winning federal research grants, publishing in scientific journals and training PhD and postdoctoral students.  Yeah right--I bet many of the old-fashioned folks wish they had patents and were able to start biotechnology companies!!!!

Until next time....

Good Luck and Good Patenting!!!!!!!

Some Tips to Reduce the Incidence of Antibiotic-Resistant Bacteria

A friend of mine accidentally gashed his leg on an open dishwasher door and thought nothing of it for several weeks until he noticed that the wound wasn’t healing and it hurt really badly. He eventually went to the emergency room at a local, where the ER docs cultured the wound and sent him home with a prescription for oral antibiotics. The antibiotics stopped working several days later and he wound up in another local hospital–this time he was admitted and the spent the next 5 days on a variety of intravenous antibiotics. Despite the treatment (they could not find the right antibiotic combination at first because  they never recultured the wound) his leg turned black from his ankle to his knee and they almost had to amputate. He is back at home now and will be treated with a regimen of iv antibiotics for the next 6 weeks or so. I talked with him last week and I learned that his leg wound is still not completely healed and the infectious disease docs are worried!

My friend almost lost his leg because of a lack of understanding about bacterial infections and antibiotic resistant bacteria and— unfortunately— because of substandard wound care treatment. With this in mind, I am posting what I think are useful tips (from the June issue of the Mayo Clinic Women’s Health Source) about how to prevent, manage and treat wound infections to minimize the emergence and spread of multiple, antibiotic- resistant bacteria.

  • Wash your hands: This simple procedure, done properly, remains the best defense. Carry alcohol-based hand sanitizers for times when hand washing isn’t possible.
  • Keep personal items personal: Don’t share towels, soap, sheets, razors, clothing or athletic equipment.
  • Sanitize linens: If you have a cut or abrasion, wash towels and sheets with hot water and added bleach. Wash gym and athletic clothes after each use.
  • Get infections tested: If an infection requires treatment, ask your care provider to take a culture to confirm what bacteria are present before you are given an antibiotic. (Editor’s note: Unfortunately, this is no longer standard practice—most infections are treated empirically which is partly responsible for the increasing frequency of antibiotic resistant bacteria.) If you test positive for a Staphylococcus (Staph) infection, ask that a culture be tested specifically for MRSA in case you need a special antibiotic.
  • Use antibiotics appropriately: When you take antibiotics, take all doses even when you start feeling better. Don’t demand antibiotics for viral illnesses; antibiotics don’t work with viruses. Taking too many antibiotics over time could become a detriment because the medication’s effectiveness can be compromised by overuse.
  • Use antibacterial products sparingly: Antibacterial soaps and cleaning products probably don’t prevent infections at home and may make these products less effective in hospitals.
  • Take precautions in the hospital: Ask all hospital staff and visitors to wash their hands or use an alcohol-based hand sanitizer before touching you. Ask care providers to wipe stethoscopes and other equipment with alcohol. Don’t set food or utensils directly on tables or beds. Make sure that intravenous tubes and catheters are inserted under sterile conditions.

I hope that these tips will help to keep you out of the hospital with potentially life-threatening, antibiotic resistant bacterial wound infections!

Until next time….

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

Should I Throw My Hat into the Ring?

After a failed attempt at getting elected to the East Windsor Town Council last Fall, I thought my days in politics were over.  But, then I received an e-mail from a friend that is causing me to reconsider a life as a politician.

Please look at this video and tell me whether you think I ought  to resurrect my political career.

 I want to thank Jack Goldenberg for his political advice and support!

until next time....

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

Pfizer and Ranbaxy Settle Lipitor Patent Dispute

As many of you may know, Ranbaxy was involved in a bitter patent dispute with Pfizer over Lipitor, Pfizer’s blockbuster multibillion, dollar anti LDL-cholesterol drug. Ranbaxy was challenging the validity of Pfizer’s intellectual property estate for Lipitor which would have extended patent protection for the drug until 2013 or longer. The patent dispute began after Ranbaxy filled an ANDA with the US Food and Drug Administration to sell generic Lipitor after uncontested Lipitor patents expire in early 2010.

Conventional wisdom suggested that Pfizer would ultimately lose the patent dispute and that Ranbaxy would be able to immediately flood the market with a much cheaper generic version of Lipitor. This would have an enormous negative impact on Pfizer’s financial stability and its future (Lipitor had $12.8 billion in sales in 2007). Nevertheless, untilDaiicho-Sankyo announced its intention to acquire Ranbaxy last week, Pfizer was willing to gamble and run the risk of losing the lawsuit. Apparently, Ranbaxy impending sale was enough of an impetus for Pfizer to settle the patent dispute which has grown increasingly acrimonious over the past year or so.

According to agreement (which needs to be approved by the US Federal Trade Commission), Pfizer was able to get Ranbaxy  to agree to delay the release of generic Lipitor until November 2011 — up to 20 months later than many analysts had been expecting (some insiders believed that generic Lipitor could reach the market as early as March 2010). Further, as part of the agreement, Pfizer will allow Ranbaxy to sell its version of Lipitor in Australia, Canada, Belgium, Germany, Italy, the Netherlands and Sweden two to four months before Liptor’s patents expire. This is likely the sweet part of the deal for Ranbaxy because all of the above mentioned markets are top sellers for anti-cholesterol drugs. Finally, because Ranbaxy was the first to file an ANDA for generic Lipitor with the FDA, it will get 6 months of market exclusivity guaranteed (in the Hatch Waxman Act) to a generic manufacturer that is first to file for generic production of a brand name drug nearing patent expiry.   However, after quickly perusing the terms of the deal, I think that it more closely resembles an authorized generics deal rather than a “true” competitive generics launch.

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An Altruism-Meter for Pharma

Just when you thought things couldn’t get any stranger, a new pharmaceutical assessment tool called the Access to Medicine Index (ATMI) was unveiled earlier this week. The ATMI is the brainchild of Wim Leereveld, a former pharmaceutical marketing entrepreneur who is CEO of the  based in the Netherlands. 

According to Leereveld, the ATMI can be used to evaluate, rate and rank a pharmaceutical company’s commitment and ability to deliver, drugs, vaccines and other medicines to patients in poor countries. In other words, the ATMI helps analysts and interested parties determine whether or not a company is doing its share to be a good corporate citizen.

The rankings are based on eight, sometimes difficult-to- interpret variables that include; 1) management; 2) influence (huh?); 3) patents (access to?) 4) R& D, 5) pricing, 6) drug donations, 7) philanthropy (isn’t this what the index is really measuring?) and 8) capacity (for what?). At present, GSK has the highest ranking and Schering Plough is dead last.

Whether or not you believe the analysis or think that the ATMI has any socially-redeeming value (remember it was developed by a former marketing executive), it is still a pretty fun tool to monkey around with. Check it out….

Until next time…

Good Luck and Good Job Hunting (try non-profits) !!!!!!!

Wake Up and Smell the Coffee

Does the smell of a fresh pot of coffee brewing get you going in the morning? Do you experience a rush of energy simply by getting a whiff of freshly-brewed joe? If you do, there may be a genetic explanation for it.

A group of scientists at Seoul National University in Korea exposed sleep-deprived rats to coffee bean aroma and then assessed the effects by performing genetic and protein analysis on their brain tissue. These results were compared with those obtained from sleep-deprived rats that were not exposed to coffee. Unstressed, non-coffee exposed and unstressed - coffee exposed rats served as controls in these experiments.

According to results published in The Journal of Agriculture and Food Science, the Korean scientists found that mRNA levels of 11 of 13 genes were elevated in the coffee-exposed rats: the levels of 2 others were decreased. They also found differential expression of proteins (using mass spectroscopy) in the two groups of rats. For example, a protein known to have an antioxidant effect was expressed at higher levels in the coffee-treated group.

So what does this all mean? According to the authors “the roasted coffee bean aroma changes the mRNA and protein expression levels of the rat brain, providing for the first time clues to the potential antioxidant or stress relaxation activities of the coffee bean aroma.” Will these observations hold true for humans? Only time will tell. That said, remember that the best laid plans of mice (rats?) and men often go astray.

Until next time…

Good Luck and Good Job Hunting (try Starbucks) !!!!!

China Impressions

I returned from my trip to China on Monday evening and I think that I am finally functioning on US time again (actually it took me less time to adjust than I expected).

China is an amazing country filled with its fair share of contrasts, paradoxes and breathtaking scenery.  From the donkey-drawn carts and traditional hutongs of Beijing to the modern skyline and hustle and bustle of Shanghai, my travel companions and I never had a dull moment in China.

The thing that struck me the most was that the Chinese people appear to be very happy and comfortable with their lives. This was shocking to me because I came of age when the People’s Republic of China was referred to as “Red China”! I expected everybody to be downtrodden and depressed. Don’t get me wrong, it is very clear that the Chinese government has complete control over its people. That said, you can basically do what you like in China as long as you understand and abide by the “rules”.  Put simply, you are free to do whatever you like in China as long as you don’t hurt anybody or openly criticize the central government. Not surprisingly, most Chinese people understand the “game” and have learned how to live their lives to the fullest despite the obvious limitations on their individual liberties. However, it is important to note that although you can visit MySpace, Facebook and other websites in China, you cannot upload blog posts (I learned that the hard way) or visit certain “sensitive” sites–they are blocked!

One of the most curious China paradoxes is the unbridled entrepreneurial and capitalistic behavior of the Chinese people that you meet on the streets or in the shops. Haggling and price negotiations are required before buying anything in China (nobody pays retail in China!). We learned very quickly that “Nothing in China is for free. But, everything is for sale!” Is China really a communist country?  That is something to ponder.

Despite its natural beauty and interesting culture, China is an environmentally-challenged country. During our 10 day visit, we saw blue skies only once. Most of the time, the air is heavy and thick and the sky is filled with dust and smog. My Chinese friends assured me that there are blue skies but mostly in winter.  

Because I am a businessman at heart, I did do a little business in China. There are still enormous opportunities in the pharmaceutical and biotechnology industries. However, the window of opportunity is beginning to close (China is beginning to outsource some of its manufacturing to Vietnam and Malaysia).  So, if you are considering starting or doing business in China, now is the time to do it!  One industry that has enormous growth potential is refrigeration and air conditioning. If you want cold anything in China, you have to ask for it—we quickly learned this after repeatedly drinking warm beers!  I don’t think this opportunity has gone unnoticed—Haier, the Chinese air conditioning and refrigeration company ( previously called it a German company until a reader corrected me)— is one of the main sponsors of the 2008 China Olympic Games!

All in all, I had a great time during my trip to China.  I loved the food, the people and the enormity of the place.  I hope that I get a chance to visit again!

Until next time….

Good Luck and Good Job Hunting (try China)!!!!!!!!!!

BioJobBlog Heads East

Well, I am off to China for a 10 day visit. Turns out that I will be visiting a Chinese pharmaceutical manufacturing facility in Shanghi.  Should be very interesting....If I am lucky I may be able to blog from China!

I hope too much doesn't change while I am away. 

Until next time....

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

Who's Who in the Biosimilar Space?

In 2004, the European Commission adopted a new directive that paved the way for legal approval of biosimilars in the European Union (EU). To date, five (5) biosimilars have garnered marketing approval in the EU. Of the five, two are generic versions of recombinant growth hormone (rHGH)–Omnitrope (Sandoz) and Valtropin (Biopartners). The remaining three are “knock off” versions of erythropoietin alpha–Binocrit (Sandoz), Epoetin alpha Hexal (Hexal) and Abseamed (Medice Arneimittel Putter).

There is no doubt, at this point, that Europe is leading the way in the biosimilar space. However, it is important to point out that a variety of biosimilars, developed by Indian generic manufacturers and others, are already being sold in less- regulated Asian markets (see Table 1). Unfortunately, political issues and the fierce struggle between innovator

Table 1. Biosimilar Manufacturers and Their Products

Company

Launched Biosimilars

In the Pipeline

Barr                                                          (www.barr.com)

EPO scheduled for launch in Eastern Europe

G-CSF (Filgastrim), Insulin, and HGH

Biocon                                          (www.bioconinc.com)

Insugen (Insulin in India and China), Erypro (EPO) G-CSF, Nimotruzmab, BIOMAb EGFR (cancer)

Insulin, glargine and HGH

Biopartners                             (www.biopartners.ch)

Valtropin (rHGH)

Alpheon (INF-α) and EPO

Cipla                                                   (www.cipla.com)

None

Autoimmune, cancer and cardiovascular

Dr. Reddy’s Labs                       (www.drreddys.com)

G-CSF (Filgastrim)

Nine (9) development programs

Glenmark                  (www.glenmarkpharma.com)

None

GBR 500 (mAb for MS), GBR600 (antithrombotic) and mAbs for adhesion molecular inhibitors

Intas Biopharma (www.intasbiopharma.com)

Neukine (G-CSF), Erykine (EPO) and Intalfa (INF-alpha2b)

Six (6) development programs

Prolong Pharmaceuticals (www.prolongpharmaceuticals.com)

None

PEG-EPO and other PEGylated proteins

Ranbaxy

(www.ranbaxy.com)

Nugraf (Filgrastim), Macrogen (Molgramostim from Zenotech)

mAbs in oncology and neurology

Sandoz

(www.sandoz.com)

Omnitrope (HGH), Binocrit (EPO)

Six (6) development programs including G-CSF (Filgrastim)

Shanta Biotechnics                              (www.shantabio.com)

Shaferon (INF-alpha2b, Shankinase (streptokinase) and Shanpoietin (EPO)

mAbs and PEGylated therapeutic proteins

Stada                                               (www.stada.de)

EPO-Zeta (approved)

Filgrastim

Teva                                           (www.tevapharma.com)

G-CSF (Filagstrim),Teva-Tropin (HGH), INF-alpha2b

Insulin, EPO and interleukins

Wockhardt                             (www.wockhardt.com)

Wepo (EPO), Wosulin (insulin) INF-alpha2b, G-CSF

Insulin Glargine

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Life, Science and Education in America

I just finished reading a  wonderful article entitled "My Son the Number" that was written by Dulcie Leimbach in  last Sunday's Education section  of the New York Times.  in it, she describes how high school students are now defined by the scores that they receive on standardized tests like the SAT and ACT and by their grade point averages and class rank.  Thankfully, by the end of the article, she posits that numbers are simply numbers and that they are not predicative of how students will perform in college or in life, for that matter.  What is most important, she says, is a student's sense of purpose and his/her ability to get along with others and finish a task at hand. Numbers, she asserts, don't measure creativity and wit and they certainly don't predict the future (something that I have learned along the way too!)

I think that if we want to improve our competitiveness in science than we ought to focus less on the numbers and more on developing a sense of purpose in student who have an interest in science. This means drastically changing the way we teach and promote science at both the primary and secondary school levels. 

I still believe that there is wonder in science and that there is also wonder in being a kid.  So, let's forget about the numbers and allow our kids be kids again! And, we just might be able to regain our edge in science!

Until next time.....

 

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

JAMA Ghostwriting Controversy Forces FDA to Reconsider New Off Label Promotion Rule Changes

As I mentioned in a post about a month or so ago, the US Food and Drug Administration (FDA) floated a proposal to ease the rules regarding promotion of off-label use of previously approved drugs. According to the newly proposed rules, FDA would allow drug makers to provide physicians with reprints of journal articles that conspicuously promote off-label uses for previously approved products. At present, drug companies are strictly forbidden to promote off-label use of their products.  A major proviso of the proposed rule changes is that the articles/reprints must be published in peer reviewed medical journals before they can be disseminated to physicians and other healthcare professionals. Apparently, FDA officials believe that peer review can take the place of the rigorous regulations and requirements that are currently in place for US approval of drugs, biologics and medical devices!

For those of you who don’t know, an editorial appeared in last week’sJournal of the American Medical Association (JAMA) that took drug maker Merck to task for using alleged ghostwriters and ghost authors on clinical studies that were published about it painkiller Vioxx. As you all know, Merck voluntarily took Vioxx off the market in 2004 after it was revealed that the drug could lead to increased risk of heart attack and stroke.

The incendiary firestorm that has ensued since the appearance of the  Although I believe that the practices of ghostwriting and ghost authoring are not as widespread as the JAMA authors would like you to believe, I think that it is a good thing that FDA may scuttle its proposed new off-label drug promotion rules.

In my opinion (humble or otherwise), drug makers MUST be required to prove that off-label uses of previously approved products  don’t pose any serious safety or health risks before companies are allowed to promote them for new indications. As we have seen time and again in recent years, safety issues and serious health risks can arise for drugs even though they received FDA approval. With this in mind I ask: “Why would FDA allow drug makers to provide less rigorous proof for an off-label indication than that required for approval of the intended use of the original product?”  It makes little sense to me. However, looking more closely at the proposed rule changes,  it would obviate the need for companies to spend additional monies (possibly hundreds of millions) to garner FDA approval for a new product indication.  Hmmm….maybe I am beginning to see a pattern here!!!!!!!

Until next time….

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

Science, Medicine and Ghostwriting

People who become scientists spend many years learning how to design, conduct, collect and analyze data from the experiments that they conduct. The ultimate goal of this seemingly endless exercise is to craft peer-reviewed publications that either support or refute the underlying hypotheses used to initiate the experiments in the first place. As part of our training, we are repeatedly reminded that it is our obligation to fastidiously and accurately report the results of our experiments and to assume “full ownership of the manuscripts and publications" that we author. The idea of allowing a person who didn’t participate in the design or execution of the research, to craft a manuscript for peer review is something that is virtually unheard of in the scientific community and, in the minds of some scientists, tantamount to scientific misconduct or fraud.

Physicians, on the other hand, who don’t learn how to conduct research or write scientific papers during their medical training, are frequently poor writers and have a little or no time to spend on writing scientific or medical manuscripts. Because of this, it is not uncommon for physicians who conduct medical research on behalf of pharmaceutical, biotechnology and medical devices companies to hire medical writers to write manuscripts for them. In fact, many physicians who work with pharmaceutical and biotechnology companies prefer and expect this arrangement. So, why the recent commotion over medical “ghostwriting”?

Drug companies typically hire medical communication agencies to develop and craft manuscripts that showcase the results of clinical or research studies that they have conducted. These companies will usually provide an agency with background information about a study, a research summary, clinical study reports, ideas or titles for proposed manuscript and a list of prospective authors (usually physicians who performed the studies on behalf of the company).  Medical writers, who are either employed by the agency or work as freelancers use these materials to craft a detailed outline for the proposed manuscript. After the outline is completed, the agency usually shares the outline with physicians who were named on the list to determine who may be interested in authoring the publication. After an author is identified, the medical writer works closely with the author to develop a first draft of the manuscript. After the draft is reviewed by the author, changes are made to the draft, a revised version is circulated and the process is repeated until all stakeholders are satisfied with the manuscript. Once the publication has been copyedited and undergone legal and regulatory review it is submitted for peer review.

For the record, in my five years as a medical writer, I have never encountered a situation where the primary author doesn’t have final say over what will and won’t appear in a manuscript. When scientific, medical or business disagreements do arise, the author(s), medical writer and company representatives usually negotiate mutually-agreed upon solutions. Rarely, have I seen a company remove an author from a publication because his/her views or interpretations of the data were not consistent with those of the company that sponsored the research. The reason why drug companies and medical communication agencies have recently come under fire for their “ghostwriting” practices is because they have repeatedly failed to disclose that many of their publications were written by medical writers —whose names didn’t appear anywhere on the publications. Although this practice still exists, it is no longer as widespread or commonplace as it once was. These days, the names of medical writers who author manuscripts routinely appear in the acknowledgement sections of many scientific and medical publications. Moreover, in some instances, a medical writer may be able to garner co-author status on a publication —depending upon his/her level of involvement in the project. 

In my opinion, there is little difference between graduate students, postdoctoral fellows and medical writers when it comes to preparing manuscripts for publication. It is not uncommon for the names of PIs, supervisors and others to appear as authors on publications even though their contribution to a project (or preparation of a manuscript) has been limited or nominal at best. Consequently, I fail to see any credible legal or ethical arguments against hiring a medical writer to write manuscript on behalf of an “author” as long as the “author” can demonstrate that he/she actively participated or was intimately associated with study design, conduct or analysis. Finally, to maintain the integrity and transparency of the medical writing process, it is imperative that medical writers who prepare manuscripts on behalf of study authors should be acknowledged or credited with “authorship” somewhere in a publication.

Until next time….

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

The Demise of RNAi?

There is mounting evidence that RNAi, once hailed as a panacea for the pharmaceutical and biotechnology industries, may not be all that it was claimed to be. Yes, there are several new RNAi drug candidates in late stage clinical development but it isn’t clear, at this point, whether any of these products will ever make it to market. Companies like Allergan, Alnylam, Opko Health and Merck, which recently bought the RNAi company Sirna Therapeutics for $1.1 billion, have invested hundreds of millions of dollars and literally “bet the farm” on RNAi therapeutics.

The use of DNA and RNA as therapeutics is not a new or novel idea. Isis Pharmaceuticals, a pioneer and champion of oligonucleotide therapeutics, has only be able to bring a single, oligonucleotide-based product to market in the past 20 years. Ask any Isis executive and they will tell you that turning DNA or RNA into drugs is a challenging process that is fraught with many difficulties. Most notably, there are bioavailability, delivery and target specificity hurdles that most be over come before the utility of these drugs as therapeutic agents can be realized. That said the attractiveness of these molecules as therapeutics (and perhaps their real danger) is the simplicity and elegance of their mechanism(s) of action. Most scientists tend to “fall in love” with elegant and parsimonious solutions to complex processes—why would we not, they are type of discoveries that we all train and live for! And, as many of us know, when people “fall in love”, there is a tendency to overlook or not notice warning signs that things may not be as they seem.

The scientific community fell quickly and deeply in love with RNAi soon after the first papers appeared touting its benefits and possible therapeutic applications. Scientists were so convinced and confident about RNAi that they induced the financial community to invest billions of dollars into the emerging technology. The love and affection for RNAi reached its pinnacle in 2006 when two scientists, who played a crucial role in discovering its mechanism of action, won the Nobel Prize. Since then, the harsh realities of RNAi drug development have begun to be realized by companies that invested in the technology.

I have been around long enough to understand that there are fads in science. In the mid 1990s it was combinatorial chemistry, in the late 1990s it was genomics, proteomics and computational chemistry and in the 2000s it is RNAi. Don’t get me wrong–all of these technologies have helped to advance science and  provide researchers with sophisticated tools that have helped to expedite the drug discovery and development process. That said, none of these technologies, by themselves, yielded the plethora of new medications or therapeutics that their advocates promised. Industry veterans know that there are no easy solutions or panaceas in drug discovery and development. The process is inherently time-intensive, painstaking and tedious. And, despite what we scientists want to believe in our “heart of hearts,” there are no guarantees that simplicity and elegance will translate into safe and effective medications.

Until next time….

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

Merck, Singulair and FDA

After weathering the Vioxx storm for the past three years, Merck again finds itself in choppy and unchartered waters. Still reeling from the Vytorin flap that erupted two months ago, there are new allegations that its blockbuster allergy and asthma medicine, Singulair, may be linked to suicide. The US Food and Drug administration (FDA) was quick (this time) to announce that it is launching an investigation into reports that suggest that Singulair may cause patients taking the medication to commit suicide. Merck received approval for Singulair in 1998 and it had sales of $4.3 billion in 2007.

There are several reasons why FDA quickly alerted the American public to its investigation into Singulair. First, FDA has been relentlessly chastised in recent months by Congress for not notifying Americans early enough in drug safety investigations. Historically, FDA has waited until the end of an investigation (rather than the beginning) before alerting the public about possible drug safety issues. Second, the agency was well aware of emerging and ongoing safety issues with Singulair. For example, over the last year, FDA regulators asked Merck to update Singulair’s label four times. These changes included information on side effects such as tremors, anxiousness, depression and suicidal ideation.

As part of its current investigation, FDA requested that  Merck “dig deeper into its clinical data on Singulair for any evidence of possible links to suicide.” Merck quickly responded and noted that none of the 11,000 patients enrolled in 40 Singular clinical trials had committed suicide. Of course this doesn’t mean that people taking Singulair didn’t think about committing suicide. In Merck’s defense, the company may not have thought to include a question about suicidal thoughts as part of Singulair’s clinical development program. Nevertheless, it is important to note that the safety profiles for many approved drugs are not fully realized until the drug has been on the market for several years. This is because the small numbers of patient used in the clinical trials for approval of a new medication are usually not sufficient to identify all  potential safety problems. Unforeseen  or unanticipated side effects typically begin to emerge only after a drug is used by larger numbers of people in the general population.  

For this reason, the Food Drug and Cosmetic Act requires that all companies that win approval for new medications are required to set up post marketing surveillance programs. The purpose of these programs is to report any and all side effects of approved drugs to the agency. The post marketing surveillance regulation stipulates that physicians, patients and drug manufacturers must report any side effects or adverse events to the agency. Based on the number of adverse events reports that it receives, FDA can launch an investigation to determine what regulatory actions, if any, should be taken by the drug’s manufacturer to deal with the safety problems. Possible regulatory actions include label changes, black box warnings, physician notification letters, Phase IV clinical trials and possible suspension or revocation of a drug license.

Luckily for Merck, the jury is still out (no pun intended) on Singulair. That said, the good news is that the drug safety and post marketing surveillance programs outlined in the FD&C act are working exactly the way they were designed to!

Until next time…

Good Luck and Good Job Hunting (avoid Whitehouse Station NJ)!!!!!!!!

The Real Problem at FDA

I spent the entire morning reading various articles, blog posts and comments about what is wrong with the US Food and Drug Administration (FDA). Not surprisingly, phrases like “drug lag”, the large size and costs of clinical trials, political and corporate influence, reduced numbers of NME approvals etc appeared ad nauseum. These are the same old, tired complaints with the agency that have been bandied about for the past 10 years or so. 

In my opinion, the bottom line is this: the agency is egregiously under staffed and under funded despite the fact that companies pay steep user fees for regulatory reviews. I can understand why corporate America is dissatisfied with the service that it receives from FDA. It is natural to expect good customer service after paying large sums of money to a service provider.  However, it is important to note, that the words “customer service” don’t appear any where in the Food, Drug and Cosmetic Act of 1938 (although it can possibly be implied fromPDUFA in 1992 and FDAMA in 1997).  Nevertheless, what is mentioned in the FD&C is SAFE and EFFICACIOUS pharmaceuticals, biologics and medical devices. Put simply, safe and efficacious products, not customer service, is REAL the mission of FDA.  With this in mind, the agency is legally required to do everything in its power to provide Americans with carefully scrutinized and safe medical devices, pharmaceutical and biotechnology products.

If we Americans want FDA to accomplish its REAL mission, then the agency must be sufficiently funded, adequately staffed and have strong, non-partisan leadership. Unless this occurs, FDA will continue to struggle and remain dysfunctional well into the 21st century.

Until next time…

Good Luck and Good Job Hunting!!!!!

Merck's Best Days May Be Behind It....Again

Oh, what a difference a couple of years or results from a pivotal clinical trial can have on a company’s financial outlook. As you may recall in 2005, Merck was in a shambles after the Vioxx scandal broke. Its CEO was ousted, its stock was trading at less than $35 per share and employee morale was at an all time low. After two short years, Richard Clark, a life-long Merck employee, was able to turn the company around. Merck’s stock reached a high of almost $61 last December and many of its employees were dancing in the streets of Rahway because their stock options were now worth more than the paper that they were printed on. But, like many things in life, all good things must come to an end.

Since December Merck’s stock price has plummeted to $40 and appears to be headed downward. What sparked the retreat was the release of results from the now infamous ENHANCE clinical trial which showed that Vytorin, which is co-marketed by Merck and Schering Plough, offered no greater benefit than a cheaper, generic version of Zocor (one of the two active ingredients of Vytorin) to reduce the risk of heart attack and stroke. The fallout from this revelation has been intense and dramatic. Both Merck and Schering Plough are being investigated by Congress for marketing violations and the financial maneuvers’ of several senior executives from both companies are under intense scrutiny. 

Many industry analysts believe that Merck may be on the ropes again and are afraid that the company may slip back into the morass it found itself in after the Vioxx debacle.

I have always held Merck in high regard–no fewer than 15 people who I went to graduate school have worked at Merck at one time or another. Further, the Merck name used to be synonymous with “second to none” science and outstanding pharmaceutical products. Sadly, over the past decade Merck’s leadership has consistently placed profits before good science causing the American public to lose confidence in one of its flagship pharmaceutical companies. Maybe Dick Clark, who was around during Merck’s glory days, can restore Merck’s reputation by insisting that from now on, good science will always come before corporate profits. Time will tell….

Until next time….

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

Enzon Pharmaceuticals For Sale?

I have been following the trials and tribulations of New Jersey-based Enzon Pharmaceuticals for the past decade. My interest in Enzon was kindled because of a friendship with Abe Abuchowski, Enzon’s former Chairman, CEO and Founder.  For those of you who may not know, Abe is sometimes called the “father of protein PEGylation” because he was first to harness the commercial power of the technology (he played a pivotal role in creating the technology as a graduate student in Frank Davis’ lab at Rutgers University).

Abe left Enzon in the early 1990s (after shepherding the US regulatory approval for Adagen®, Oncospar®, and PEG-Intron®) and in 2004, he (along with my help) founded Prolong Pharmaceuticals, a biopharmaceutical company that specializes in PEGylation of biogenerics. Prolong is also using protein PEGylation to create new antimicrobial and blood replacement products.

Over the years, Enzon has had its share of “ups” and “downs.” Although profitable through much of the 1990s, Enzon is now a company riddled with huge debt– mostly because of bad decisions made company executives in the post-Abuchowski era.  Since 2004, Enzon’s Chairman and CEO, Jeffrey Buchalter, has worked diligently to “right” the company. He realigned and focused the company’s strategic objectives and, through some creative financing, reduced some of Enzon/s more onerous debt obligations. To that end, he was able to restore shareholder confidence and stabilize Enzon’s stock price. Unfortunately, Jeff’s efforts may not be enough to save the company from acquisition or merger.

Many industry insiders believe that Buchalter was hired four years ago to prepare the company for sale. Yesterday, Enzon disclosed in a SEC filing, that the self-proclaimed biotech maven, Carl C. Icahn, increased his Enzon stock position from 1,760,001 to 3,072,103 shares. After the purchase, Icahn owns about 6.93% of the company’s outstanding shares and is one of its largest, single shareholders. Not surprisingly, Icahn now wants the company to consider putting itself up for sale. Maybe the insiders were correct in their thinking?

Stay tuned for more details.

Until next time….

Good Luck and Good Job Hunting (forget New Jersey)!!!!!!!

The FDA New Drug Approval Conundrum Revealed

FDA approvals of biopharmaceutical products have decreased in recent years. This includes recombinant proteins and monoclonal antibodies and cancer therapeutics. In the decade from 1996-2005, an average of 16.6 new drugs were approved each year. In marked contrast, there were only 11 and 12 new medications approved in 2006 and 2007, respectively.

Last year was an unusually unproductive year for the pharmaceutical and biotechnology industry. The combined sales for products approved in 2007 are projected to be less than $1.0 billion dollars–the benchmark for drugs that receives blockbuster status. Further, most or the approved drugs were similar to ones that were previously approved (so called “me too” drugs) and none will significantly improve healthcare for large numbers of patients.  Finally, only two recombinant protein drugs were approved in 2007–a level more representative of the 1980s.

Most analysts agree that it is unclear why FDA approval of new drugs has decreased over the past few years and who, if anybody (FDA and/or industry), deserves the blame for the approval drop-off. Regulatory filings for a number of new products are either expected or currently pending. To that end, it is likely that there will be more new approvals in 2008 and 2009 as compared with previous years. To learn more about the drug approval conundrum please read this article recently written by Ronald A Radar.

The rate of new approvals must increase in order for the biopharmaceutical and pharmaceutical industries to remain economically healthy and viable. Industry and the FDA must work more closely with one another to continue to insure that the American public has ready access to innovative, safe and efficacious, new biopharmaceutical and pharmaceutical products. 

The EPO Saga: The Demise of a Blockbuster Drug

Erythropoietin (EPO) is a hormone (protein) that regulates red blood cell production in humans. Back in the 1980s, scientists at a fledgling biotechnology company called Amgen determined that recombinant EPO was highly effective for treating anemia. Amgen owned the intellectual property rights to the EPO gene and decided to sell the recombinant protein encoded by EPO (called epoetin) as a treatment for anemia.EPO is known to alleviate fatigue caused by anemia by stimulating red blood cell production.

Amgen’s first EPO product, called Epogen, was approved in 1989 to treat patients suffering from anemia associated with renal failure. Procrit, Johnson and Johnson’s version of EPO (which was licensed from Amgen) was approved four years later in 1993 to treat chemotherapy-induced anemia. Aranesp, a longer acting version of EPO which is also manufactured by Amgen was approved in 2001 for anemia associated with chronic renal failure and in 2002 for chemotherapy-induced anemia in cancer patients.  All of the EPO drugs have gained blockbuster status and, over the past five years or so, the annual revenue generated by these drug is estimated to be $6.0 to $12 .0 billion.

Since their approvals, EPO, Aranesp and Procrit have been administered to tens of millions of kidney dialysis and cancer patients undergoing chemotherapy with minimal safety concerns and generally positive outcomes. However, with the looming specter of generic biologics (EPO lost patent protection in 2004) and competition from companies like Roche developing competing EPO products, Amgen stepped up its efforts to promote and sell EPO and Aranesp. This, in turn, caused EPO drugs to be used by many physicians, which ultimately resulted in additional safety warnings and a label change for all EPO products. The label change coupled with unrelenting negative publicity about Amgen’s promotion of its EPO franchise, caused its stock price to plummet and forced the company late last year to lay off 14% of its workforce.

Like other biotechnology and pharmaceutical companies, Amgen sought to find ne indications for its EPO products. To that end, there was some compelling evidence several years ago which suggested that EPOmight increase survival of cancer patients, when used with radiation and chemotherapy. The idea was that higher oxygen levels in the blood would make the radiation or chemotherapy being used to treat the patients' cancer more effective. With this in mind, several groups of investigators initiated human clinical trials to determine whether EPO treatment would benefit non-anemic cancer patients. Unfortunately, the New York Times reports that results from no fewer than eight clinical trials suggest that EPO drugs might actually promote rather than slow tumor growth and hasten the death of cancer patients.

Continue Reading...

"Survival of the Fittest": Keeping Your Job in a Recessionary Economy

I happened upon a Sunday morning talk show yesterday where one of the guests was discussing strategies that employees ought to adopt to keep their jobs in a recessionary economy. For those of you who haven’t been paying attention, the US economy lost 63,000 jobs last month; another bit of evidence that we are sliding into an unavoidable recession. 

The talk show guest posited that only those employees who were able to quickly adapt to rapidly changing corporate/business environments would keep their jobs; the other less adaptable employees would find themselves jobless. Call me crazy, but his analysis sounded eerily similar to Darwin’s principle of natural selection or “survival of the fittest”–only those members of a population who were able to adapt (through mutations in Darwin’s case)  to changing environmental conditions will survive; the other less adaptable members will perish. Imagine that, using a recessionary economy to illustrate one of the fundamental principles of Darwin’s theory of evolution–how cool is that?

Here are some insights into how to keep your job during a recession when many companies are unstable and in flux. First, employees who work at financially-troubled companies must embrace the changes frequently instituted by management whether or not they agree with them. Invariably, there will be a cadre of employees who openly and publicly criticize the “new corporate policies”–these will likely be the employees who are demoted or “right-sized” out of the company.  In Darwinian terms, these employees are unable to adapt to change and they will either be eliminated or their standing in the population (company) will be diminished.  On the other hand, the employees who are able to embrace change will not lose their jobs and will likely be able to maintain or improve their standing in the population (company).  In other words, adaptable employees have a selective, competitive advantage over unadaptable ones which will allow them to survive and flourish in their new environment. Second, it is probably not wise during periods of corporate upheaval, for mid-level managers or employees to tout their past accomplishments or remind management about their worth to the company. In times of change, management embraces individuals with forward-looking ideas (to facilitate change) not those who are rooted in the past and are invested in antiquated corporate policies and practices. Again, only those employees who adapt will be able to survive and compete in their new corporate environment.  Finally, as a science educator, it is always exhilarating and exciting to find new ways to teach Darwin’s Theory (sic) of Evolution so that it makes sense to lay audiences. Maybe watching Sunday morning talk shows isn’t a waste of time after all!!!!

Until next time… 

Good Luck and Good Job Hunting (adapt)!!!!!!!!!

What to Look For in a "Bad" CEO

According to Terry Leap, a Professor of Management at Clemson University, CEOs that exhibit some or all of the following traits or behaviors are likely to be problems.

  • An obsession with acquiring prestige, power and wealth
  • A reputation for unwarranted and shameless self promotion
  • A tendency to propose “grandiose strategies” and failing to include a detailed plan to carry them out.
  • A superb ability to compartmentalize and rationalize things.
  • A history of emphasizing activity, like hours worked or meetings attended, over accomplishment.
  • A reputation for implementing major strategic changes unilaterally or for forcing programs down the throats of reluctant managers.
  • An impulsive, flippant decision–making style.
  • A love of monologues coupled with poor listening skills.
  • A tendency to display contempt for the ideas of others.
  • A penchant for inconsiderate acts

The thing that worries me is that many academicians and most CEOs that I know exhibit five or more of these traits. Oy! 

Until next time…

Good Luck and Good Job Hunting

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