Oversaturation vs. tunnel vision

One of the things that drives me nuts when I go to the grocery story is heading down the aisles and seeing a slew of new products that seem to be designed solely to part me with my money and make less space for established items that I already like more than they do to enhance my life. Truly, I have to wonder if adding marshmallow bits to a cereal or making a chocolate version of a healthy oat-based staple of the breakfast table is really necessary. And cheeseburger flavored Doritos? Don’t get me started.

I admit that I sometimes feel the same way when I see multiple iterations of drugs, whether over-the-counter or prescription, or when I see large-scale research efforts that cover the same ground but with different budgets and different researchers.

Then I realize that it’s just that growing “grumpy old guy” persona that started to kick in just before I officially entered middle age. Yes, sometimes pharma companies do simply re-tool a product or create a knock-off version of something for the sole purpose of capturing market share and providing something that seems new but really isn’t.

But so many other times, products that seem similar (particularly when it’s a new chemical compound from the same company for the same target or a similar-acting one from a rival company) need to be pursued for the very reason that subtle differences can have big impacts in terms of efficacy, adverse reactions and off-target effects. I was reminded of that in writing a story yesterday for the web site on Amarin’s promising new omega-3-based triglyceride-lowering drug, which on the surface seems a lot like GSK’s Lovaza.

On the research side, I also got the reminder of how looks can be deceiving when I wrote two stories for the upcoming December issue of ddn that cover the 1000 Genomes Project and the PGP-1K, respectively. When you have two high-profile projects doing complete human genome sequencing with the magic number 1,000 involved, you start to ask questions like: “How is your project different from that one?”

But the fact is that they do have different focuses and different approaches, and because of that, they aren’t duplicated efforts that are redundantly spending money, but rather two projects doing work that will likely provide support to each other’s efforts in the long run, as well as each provide distinct and unique contributions to genomics.

Because, in the end, if there’s anything we’ve learned from decades of pharma and biotech breakthroughs, failures and other newsworthy outcomes, the human body and human diseases are an arena where we aren’t ever likely to have all the answers, and might be lucky to get even a handful of them, no matter how many similar or even duplicative efforts we have.

Too much money poured into certain areas, even important ones like cancer, can mean oversaturation and dilution of research dollars that might be needed on other disease areas. But too little diversity in the research and development sphere, and we can end up with tunnel vision…and look where that got us when we took our eyes off new antibiotic research and ended up with a whole lot of resistant pathogens and not enough ways to fight them.

Gobble, gobble…but not too much, now

Those of you in Canada already celebrated your Thanksgiving Day in October. I’m not sure how many nations outside of North America even have such a celebration.

But I can probably rest assured that the residents of the United States will understand why there aren’t likely to be much in the way of updates this week, as our day of (American) football, turkey, stuffing, mashed potatoes, gravy, green bean casserole, pumpkin pie, family, friends and other things for which to give thanks is on Thursday (Thanksgiving Day). So, Wednesday of this week is scrambling to get my ddn work done and bake my Pumpkin Crunch dessert (a dish that has won me many a friend), Thursday will be a day to enjoy the holiday, and Friday will be the continuation of the long weekend that begins Thursday.

Sure, it’s entirely possible that some pharma news will crop up or an idea will burrow into my head and cause me to post something before Monday, but if not, see you next week, and here’s hoping not too many of us need to move up one or two belt notches over the coming several days.

For M&As right now, Glaxo seems a no-go

I know I reported on this in early September (right here), but apparently the news bears repeating—and elaboration—since the company in question is again being pretty blunt about its view of M&As right now:

GlaxoSmithKline doesn’t want to acquire Genzyme.

Either that, or GSK is engaging a stealthy distraction of such grace and magnitude that it would make a team of elite ninjas commit ritual suicide in jealous disgrace.

Glaxo, of course, has been noted as one of several companies contacted by Genzyme to determine its value as it fends off an $18.5 billion hostile takeover bid by sanofi-aventis. But speaking late last week to reporters in Cambridge, Mass., where Genzyme is based, Patrick Vallance, senior vice president of medicines discovery and development for GSK, along with other Glaxo executives, gave an overview of their drug discovery and development strategies, and they were pretty clear that large M&A deals aren’t really a focus right now.

Vallance described such big deals as often being destructive to R&D efforts, and instead Glaxo has been toying with some new business models in discovery and development to reduce its risk and maximize its successes, something I’ll touch upon in the coming days and weeks as I share information from GSK R&D Day last week in Cambridge, which I had the pleasure to attend along with other members of the mainstream, business and pharma media.

GSK is increasingly looking outward for new ideas and new compounds to fill its pipelines, but it doesn’t seem eager to want to just buy companies based on potential, and certainly not for huge sums, as Moncef Slaoui, the British pharma’s head of research and development, noted when he said in September that “An offer by GlaxoSmithKline for Genzyme does not make sense. It is too expensive.”

So, for those still holding out that GSK is simply waiting to pounce in from the shadows to duel with sanofi over Geznyme, you’d probably be better making a bet that Glaxo might make a partnership deal with the company one day. Because Vallance and Slaoui have both been pretty clear that GSK is willing to look for the best ideas outside the company, but it isn’t that fired up about spending a mint to bring them in-house unless they look like they’re already on the way to big payoffs.

Putting a face on diabetes isn’t too hard

In my role with ddn, whether in the print publication or the online venues, I get to write about myriad diseases that affect the human population on this planet.

From Huntington’s and Alzheimer’s diseases to diabetes and cancer, companies that we cover each month are working to find new ways of battling these insidious diseases.

In talking with many of the people on the front lines of the research effort to develop these treatments, I get to put a name and face to efforts to improve our chances of surviving and thriving when these illnesses strike.

Over the years, the pages of ddn have featured stories about diseases that strike particularly close to home for those of us writing the articles. For me, it’s diabetes.

November is Diabetes Awareness Month, and it serves as a reminder for us all of a disease that is a growing problem.  According to some health studies, by 2050, one in three adults could be diabetic.

Today, nearly 24 million Americans have diabetes – including an estimated 6 million Americans who have it and don’t know it. It is estimated that another 57 million adults in the U.S. have pre-diabetes, placing them at increased risk for developing type 2 diabetes. Type 2 is the most common form of diabetes, accounting for 95 percent of all cases.

I don’t have to look too far to put a face on diabetes. My wife was diagnosed with type 2 diabetes just over a year ago. Her father was diagnosed five years ago, but he lived with the disease for many years and didn’t know it, choosing to ignore the warning signs.

As a result of years of living with uncontrolled diabetes, my father-in-law today is 64 years old, legally blind and must undergo kidney dialysis three times a week. For him, it’s a matter of life or death.

After being diagnosed, my wife felt as if she were just handed a death sentence. I knew from the stories I’d written that there are two ways to live – you can control the disease or it can control you.

We’ve learned that type 2 diabetics can take a number of oral medications to help their body metabolize sugars, increase insulin production or block the absorption of carbohydrates.

My wife also has a key advantage over her father in her fight against diabetes – early detection. While a diagnosis is a life-changing experience, knowing the what you’re up against is instrumental in effective treatment.

It also is key in thwarting the ravages of diabetes, which include neuropathy, which causes tingling, numbness and destruction of nerves. Because of neuropathy, diabetics must check their feet regularly to ensure they have no wounds. If undetected, a wound can lead to infection that could lead to amputation. Diabetes may also lead to kidney disease, heart disease and blindness.

We’ve learned from the endocrinologist that the goal of diabetes treatment is the prevention of long-term complications. We’ve also had to talk to dietitians and diabetes educators, learning that it truly takes a village to keep a diabetic well.

I’ve learned that even a simple trip to the optometrist can heighten anxiety in my wife. She has her father as a constant reminder of what can happen with this disease.

Type 2 diabetics can take a number of oral medications to help their body metabolize sugars, increase insulin production or block the absorption of carbohydrates, and that’s where we are at. Thanks to the work of countless researchers over the decades, these treatments are available to help diabetics keep their blood sugar levels in check.

Researchers today are at work to discover new drug candidates that have greater efficacy against these diseases. Stepping outside of my role as a journalist and speaking as a husband and father, I have to say just how grateful I am for the work of these researchers. Whether you work at the biggest pharma or the smallest of labs, your work is having an impact on the lives of people the world over.

Some of you may even be motivated in the lab by your own personal experience. We all can share that common bond in the human condition. The faces of these diseases are all around us, and the battle is no less important today. That key discovery that could deliver the knock-out punch to a disease could be occurring in a lab right now.

And to all of the researchers who toil each day to find the Holy Grail, I thank you.

Social butterflies

Corporations are sometimes a bit slow to pick up on technological trends, particularly when it comes to information technology. They might be somewhat behind the curve on their IT systems, and it is not uncommon for them to be really behind when it comes to an online presence. Even though so many have websites, many companies often don’t put much thought into how those site can help them and help clients, customers, partners and investors (or media, for that matter).

I’d say most of the Big Pharma and even mid-sized companies I’ve run across pretty much “get it” in terms of websites (and many smaller companies, too, though I’m shocked to find every few months a young biotech that seeks media and investor attention yet fails to have at least a rudimentary website). Well, aside from photos archives. As a member of the media, I urge more pharmas and biotechs to take good headshots, facility shots and candid shots of employees (lab workers, for example) and have them easily downloadable online in high-resolution formats. I’ll never understand why so many huge companies fail to offer that.

But I digress.

What I wanted to get at was the social media options, an area in which so many companies just miss the boat entirely, both inside and outside of pharma. With Twitter, Facebook and LinkedIn, just to name three biggies, there is no excuse for a company not to at least try to make good use of at least one, and ideally more than one. To not use social media in some way seems a sure way to show that you are behind the times. Blogs, too, are an important area to consider, either separate from or integrated into the company website.

Not everyone will use social media to the best of their potential, but then again, they don’t need to get it perfect. Not everyone nails it with marketing/advertising, employee communications, project management or public relations, either. We can’t all be good at everything.

But every company should be somewhere in terms of social media, and in that vein, I wanted to share a roundup with you of some “top 10” efforts by pharmas in the realm of social media posted on slideshare.net. It shows some notable example of what has been done by Johnson & Johnson, Glaxo-Smith-Kline, Bayer, sanofi-aventis, Novartis, AstraZeneca, Bristol-Myers Squibb, Roche, Pfizer  and Boehringer Ingelheim.

Sure, the original post was put up two years ago, but it still serves as a good example of what pharmas can do with social media, when they put their minds (and sometimes hearts) into the effort:

Click here to see the slideshow.

For stem cell case plaintiff, faith and science go hand-in-hand

Yesterday, we shared a Q&A with the lead plaintiffs in the controversial federal lawsuit challenging federal funding for embryonic stem cell (eSC) research, Dr. James L. Sherley, a biological engineer at Boston Biomedical Research Institute, and Dr. Theresa Deisher, research and development director at AVM Biotechnology LLC in Seattle.

Both researchers agreed to field questions about their beliefs regarding eSC research. Deisher, who has been especially vocal about her Catholic faith and how it informs her research, also agreed to take a few questions about the connection she sees between her beliefs and science.

According to Deisher’s bio, she has 17 years of experience in scientific and corporate leadership positions involving research, discovery, production and commercialization of human therapeutics. She obtained her Ph.D. in molecular and cellular physiology from Stanford University. Prior to founding AVM Biotechnology in 2007, Deisher held positions at Repligen Corp. in Cambridge, Mass., ZymoGenetics Inc., Immunex and Amgen in Seattle and CellCyte Genetics Corp. in Bellevue, Wash. She has had 23 patents issued and has published numerous scientific manuscripts.

ddn: Do you find any conflict between your faith and the scientific research you engage in?

Deisher: I do not find any conflict between my faith, which is Catholic, and my research. My faith enhances my work. My Christian faith calls me to focus on drugs and treatments that are affordable so that the greatest number of people will benefit. My faith calls me to use reason and the order of natural law to determine, for instance, the stem cell most optimal for clinical use. My faith calls me to focus only on those treatments that will be effective. My faith also calls me to respect the intrinsic dignity of human life in my work.

ddn: How does your faith impact your research approach?

Deisher: My faith is completely complementary to my research, which focuses currently on stem cells for regenerative medicine and alternative vaccines.

Adult “self” stem cells, meaning a patient’s own stem cells, are affordable, compared to all other stem cell therapies. For the most part, therapies using adult stem cells will cost about $25,000 compared to Geron’s projected $500,000 for embryonic stem cell-based therapies. Adult “self” stem cells are found naturally in every organ, in each of us, and they are “preprogrammed’” to perform the functional regeneration that patients require. They also lack the issues of immune rejection or tumor formation that plague pluripotent stem cells such as embryonic stem cells. Adult “self” stem cells are far advanced in clinical trials, and in comparison to “patented” stem cell lines, they show more effectiveness in patients. Whether one believes in God or Darwin, one can arrive at an optimal stem cell for patients using objective measures, common sense and business criteria to generate the greatest good for the most people.

I would apply these same criteria to any type of treatment that I would work on, including biologics and small molecules: Will the therapy be affordable, or will only the very few benefit? Will the therapy be effective or merely enhance my stock price or financing temporarily? Will the therapy be undermined by adverse side effects? These criteria are sound business objectives and compatible with my faith.

Q+A with the stem cell case plaintiffs

On the cover of our November issue (which you can download here), you can read about a controversial lawsuit that is at the center of one of our nation’s hottest current debates: embryonic stem cell (eSC) research. (See the story here.)

The lawsuit, Sherley, et al., v. Sebelius, et al., alleges that the order signed by President Barack Obama in March 2009 lifting a previous ban on federal funding for eSC research violates the Dickey-Wicker amendment, a 1995 law prohibiting the government from appropriating funds for research that involves the creation or destruction of human embryos for research purposes. The lawsuit also contends that President Obama’s order has intensified competition for government research funds—which are already in short supply—for researchers engaged in other kinds of stem cell research.

The case has been making its way through the courts for a while, but it made headlines in August when the U.S. District Court for the District of Columbia issued a preliminary injunction in the case, essentially bringing funding for embryo-destructive research to a screeching halt while the case is under consideration.

With the research community in uproar over the decision, less than a month later, the U.S. Court of Appeals temporarily suspended the injunction, arguing that it would cause irreparable harm to researchers, taxpayers and scientific progress while the case is appealed.

While Sherley v. Sebelius concerns the interpretation of law and competitive issues, the case has renewed the debate over the practice of stem cell research in the United States, a political and moral tug-of-war that has been waged for decades.

The debate centers on the creation of a human embryonic stem cell (eSC) line, which requires the destruction of a human embryo. Advocates of the pro-life movement are concerned with the rights and status of an embryo as an early-aged human life and equate eSC research with murder. Those opposing this view argue that these embryos are to be destroyed or stored for long periods of time past their viable storage life, and point out that stem cell research has the potential to dramatically alter approaches to understanding and treating diseases, and to alleviate suffering.

Science holds pros and cons for both sides of the moral debate. Adult stem cell research has achieved great levels of success and potential, but these stem cells are generally limited to differentiating into different cell types of their tissue of origin. Although some researchers are of the opinion that the differentiation potential of eSCs is broader than most adult stem cells, they may be rejected by the immune system—a problem that would not occur if a patient received his or her own stem cells.

Dr. James Sherley

As the case continues to play out in court, media attention is turning to the lead plaintiffs in the case, Dr. James L. Sherley, a biological engineer at Boston Biomedical Research Institute, and Dr. Theresa Deisher, research and development director at AVM Biotechnology LLC in Seattle. Although the pair admit they did not know each other prior to the case unfolding—they were reportedly “recruited” by attorneys seeking to challenge President Obama’s order—they both have certain beliefs about the ethics involved in eSC research, and strongly support a focus on adult stem cells.

Sherley, whose research focuses on the molecular and biochemical mechanisms of adult stem cells, has long been vocal about his opposition to human eSC research. He has described the position that eSCs hold the promise to cure or treat debilitating diseases “misinformation,” maintaining that adult stem cell research is “a viable and vibrant path to new medical therapies.” Sherley also once made headlines for protesting a decision by the Massachusetts Institute of Technology (MIT) to deny him tenure by going on a 12-day hunger strike. Sherley, who is African-American, has also publicly said he believes that MIT did not give him the freedom to challenge scientific orthodoxy the way the institution would have for a white colleague.

Dr. Theresa Deisher

Deisher, who works exclusively with adult stem cells, founded AVM Biotechnology “in response to growing concerns about the need for safe, effective, affordable and ethical medicines and therapeutic treatments,” with help from private donors. According to the company’s website, “The use of aborted fetal tissue and embryonic cells in the discovery, development and production of vaccines and pharmaceuticals … make it difficult for many physicians, pharmacists, scientists and healthcare professionals to navigate their fields of expertise without sacrificing their consciences.” You can see some of Deisher’s writing on the subject here.

As media scrutiny has intensified in the wake of the case, Sherley and Deisher have backed away from many interviews, but were gracious enough to take questions from ddn regarding their views about eSC research. Here are their responses:

ddn: What should the goal of stem cell research be?

Sherley: Like other NIH-funded research, the goal should be to increase our scientific knowledge about the natural world through the conduct of ethical scientific research towards the goal of improving human health.

Deisher: The goal should be to develop safe, effective and affordable therapies for human disease, adhering to the highest scientific ethical standards.

ddn: Are you against embryonic stem cell research as a practice, or the federal funding of it, or both? Why?

Sherley: Specifically, I wish to educate and alert the public that, first and foremost, human embryonic stem cell research is unethical according to pre-existing NIH guidelines for human subjects research; that its funding by NIH is illegal according to U.S. law as articulated by the Dickey-Wicker amendment; and that it continues to be misrepresented by many of its proponents who misstate its potential for providing medical advances and present it as if there were no alternatives, when if fact both adult stem cell research and traditional disease research are not only effective alternatives, but better ones in many respects.

Deisher: Human embryonic stem cell research does not meet the high ethical standards test. A human being is necessarily destroyed in the process of obtaining human embryonic stem cells, which is not an acceptable outcome according to U.S. human subjects guidelines. Additionally, the research is not necessary, another requirement of our human subjects guidelines, as superior alternatives are available using adult stem cells. According to human subjects research guidelines, even if parents give consent, research cannot be done if it is not necessary. Human subjects guidelines should be applied to all research, regardless of funding source, and should be applied to regulate research on human embryos.

ddn: What are viable alternatives to embryonic stem cells? How soon will they bring about therapies? What is their commercial potential?

Sherley: The viable alternatives are both adult stem cell research and traditional disease research. In particular, adult stem cell research addresses the development of new therapies based on repairing tissues or replacing tissues with regenerative cells. Such therapies based on adult stem cells are already a part of standard clinical practice. Bone marrow reconstitution with blood stem cells is one of the best known examples, but there is a large body of clinical research underway both to make blood stem cell treatments even more effective and to develop new therapies based on other types of adult stem cells. This clinical research includes commercial development of therapies for diseases like diabetes based on developing adult stem cells that renew the cells that make insulin. It is important that the public understands that proposed treatments based on human embryonic stem cells invariably require that they be converted into either adult cells or adult stem cells, which are ultimately required for any therapy that will repair, replace, or treat tissues in children and adults. When the public knows this, it then becomes imperative for it to ask proponents of human embryonic stem cell research, “What is your motivation?”

Deisher: Adult stem cell therapies are in late-stage clinical trials, having advanced extremely rapidly since their discovery in the late 1990s, entering clinical trials by 2002.  Prior to the late 1990s, scientific dogma held that adult stem cells did not exist outside of the blood system. These novel discoveries have brought promise to many patients suffering from grievous illness; unfortunately, the United States lags behind the rest of the first world in advancing these therapies because our academic scientists and elected officials have preferentially advanced human embryonic stem cell research, which is currently helping no one. Other alternatives include therapies that block tissue destructive pathways. For instance, Enbrel is a drug for rheumatoid arthritis that blocks the joint destroying action of a molecule called TNF. Once the destructive pathway is blocked, naturally present regenerative processes are able to replace the damaged joints.

ddn: Describe some of your current work in this area.

Sherley: My laboratory’s research is focused on developing methods for production of adult stem cells, discovering biomarkers that can be used to quantify adult stem cells, and elucidating cellular mechanisms that are important for adult stem cell function, health and longevity.

Deisher: My research focuses on the efficient delivery and retention of stem cells in diseased organs.

ddn: What should the government’s role be in stem cell research being done in the United States?

Sherley: Through its agent the NIH, its role should be the same as for other areas of research: Adhering to U.S. law, foster and fund ethical, high-quality research that has potential to positively impact human health.

Deisher: (References the NIH’s mission statement, which states, “NIH’s mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life and reduce the burdens of illness and disability. The goals of the agency are: To foster fundamental creative discoveries, innovative research strategies, and their applications as a basis for ultimately protecting and improving health; To develop, maintain and renew scientific human and physical resources that will ensure the nation’s capability to prevent disease; To expand the knowledge base in medical and associated sciences in order to enhance the nation’s economic well-being and ensure a continued high return on the public investment in research; and to exemplify and promote the highest level of scientific integrity, public accountability and social responsibility in the conduct of science.”)

Highlighted in red are NIH mandates that are not met by NIH funding of human embryonic stem cell research. The government’s role should be to actively promote research and clinical trials in areas that would not be adequately advanced by private industry. Adult stem cells from a patient’s own blood, bone marrow or other organs are not patentable, and therefore, absolutely require federal funding to bring these remarkable treatments to U.S. citizens. As taxpayer funds are used by the government for these purposes, one would hope that affordability would also be an important criterion for federal funding of clinical trials. Adult stem cell therapies are affordable, and will cost on average about $25,000, while embryonic stem cell therapies, if ever available, will be expensive and beyond the means of almost all U.S. taxpayers. Geron Corp. issued public statements in January 2009 estimating the cost of human embryonic stem cell-based therapies for spinal cord injury to be just under $500,000. Geron received significant NIH funding for this work.

ddn: How does the 2009 executive order from President Obama impact your access to research funds?

Sherley: Because the president’s order led to NIH instituting the illegal funding of human embryonic stem cell research, it injures all U.S. scientists working in other fields who compete for the same limited NIH resources. However, the greater injury is sustained by scientists whose research focuses on the recognized alternative to human embryonic stem cells, adult stem cells, because of the juxtaposition of all stem cell research applications in the NIH review process. At each phase of the NIH review process, bias and contempt, inspired by an illegal implementation of the president’s order, can occur against their research applications, even though they may be of the highest quality.

Deisher: The executive order initiated a process where preference in NIH requests for grant proposals and ultimate grant funding is now directed towards embryonic stem cell research. The 2009 executive order amplified congressional obsession with funding embryonic stem cell research, apparent since 2006. Every adult stem cell scientist and clinician is injured by the preferential emphasis and funding of embryonic stem cell research. Most egregiously, U.S. citizens are being denied adult stem cell therapies that are in development in Europe and other countries for heart attack, blindness, paralysis, stroke, diabetes, multiple sclerosis, lupus and other grievous human illness.

ddn: What can Americans do to get past the moral arguments in favor of or against embryonic stem cell research, in order to make sure that we are still working toward finding cures for devastating diseases and conditions?

Sherley: Americans would have no dilemma to ponder, if they were better informed that human embryonic stem cells have very little potential to lead to cures for devastating diseases and conditions. The No. 1 sales pitch pushed for these cells, the “ability to make any cell in the body,” is their fatal flaw for providing new medical therapies. For effective tissue and organ therapies, regenerative cells are needed that can continuously replace the mature cells found in just the sick or ailing tissue or organ. Human embryonic stem cells cannot do this. Adult stem cells can. Since human embryonic stem cells make other cells that are not needed, if they were used, they would give the patient another well-known, very difficult-to-treat disease.

Deisher: Science should never be above moral scrutiny and one only needs a brief history lesson to know this. On another note, I hear arguments regularly that we should not deter human embryonic stem cell research because of the moral objections of a minority. This is absurd, as our entire scientific research ethical oversight is predicated on respect for the moral objections of a minority in our country. Respect for animal rights and concern for ethical research conduct using animals in experiments regularly deters experiments that are scientifically and economically expedient. Respect for ethical concerns as they relate to human subjects research should receive no less deference. However, Americans do not need moral arguments to oppose embryonic stem cell research; embryonic stem cells are known to form tumors, they would require lifelong immune suppression that itself can cause hypertension, osteoporosis and other nasty side-effects, and human embryonic stem cell products would be too expensive for Americans to afford.

Deisher was also kind enough to field questions about how her Catholic faith informs her approach to stem cell research. We’ll bring you that Q&A very soon.

Genzyme and sanofi continue on…and on…and

There is a good reason why professional arm wrestling isn’t a major television draw. For all the complaints of how boring baseball or golf is to watch, things do change and tides turn in dramatic fashion amid the slow portions. But watching two people with interlocked hands staring each other down while muscles bulge…until finally one opponent just loses the will or strength to continue?

No, not interesting to most people.

In many respects, the sanofi-aventis attempt to acquire Genzyme (whether by willing merger or takeover) is beginning to feel like arm wrestling. It’s only interesting if you’re one of the competitors. Or you have a bet placed.

So, in recent days, sanofi has once again invited Genzyme to come to the table and talk (see this story coming out of Boston, for example, or this one from the Wall Street Journal). Genzyme, in turn, has said “There’s not enough money on the table yet to convince us show up!” (I paraphrase wildly, of course). We’ve been held at a $69 per share offer so long, and the back-and-forth repetition from both sides as to why they won’t budge that…Zzzzzzz

Wha….! Huh?!!!!

Seriously, though, as repetitious as this is seeming, there are little gems of information and insight to be gleaned.

For one thing, despite inviting Genzyme to come back to the table after threatening to take them over, sanofi is still showing its assertive streak by warning the Cambridge, Mass.-based company not to turn to its state’s takeover protections and swallow the proverbial “poison pill” to fend off a hostile acquisition (see this Bloomberg story).

At one website where the latest overtures and refusals had been aired as news, a comment was posted that said, essentially: “Maybe it’s time for sanofi to walk away long enough for Genzyme’s shares to drop back into the 40s and then let Genzyme’s top brass explain the real value of their shares to the stockholders.”

I don’t know that I agree Genzyme isn’t worth more than $69 per share. Maybe it is, maybe it isn’t. But it is certain that the stock rose on the news of a sanofi merger (or takeover). The continued presence of sanofi as an eager suitor (or conqueror) doesn’t seem likely to drive down stock prices. One can only wonder whether with no rival suitors sanofi might be better off stepping away for a time. But then again, with the pressures Big Pharma is facing right now with patents expiring and pipelines being sluggish, perhaps sanofi can’t afford to do that.

It’s also worth putting the current situation into perspective relative to sanofi’s third-quarter earning report in late October. Commenting on those earnings, which were up 13 percent, analyst Simon King of Datamonitor wrote:

“Sanofi-Aventis’s increasing diversified business model is reaping rewards as growth across consumer, generic and vaccine divisions has helped to compensate for generic competition within the branded pharmaceutical segment. However, generic erosion continues to impact performance, driven in part by the somewhat unexpected approval of a generic Lovenox product. With Plavix sales also in decline due to loss of European patent exclusivity, Sanofi-Aventis’s anti-thrombotic empire is in collapse.

“These results occur against a backdrop of continued negotiation regarding Sanofi’s proposed acquisition of Genzyme. Sanofi has used its results announcement to launch its latest salvo towards Genzyme shareholders by suggesting that nothing has been said that will change its current offer. Genzyme though is now being very bullish in terms of sales forecasts – which will be heavily dependent on reversing the loss of sales to Shire in specialist markets and the success of Campath in multiple sclerosis.”

King notes that Genzyme’s stance could backfire, particularly if sanofi does decide to walk away and no other bidders emerge. However, he remains convinced that the Genzyme acquisition “fits the sanofi model.”

For now, it’s still an arm wrestling match. We’ll keep our eyes on it, and let you know who wins in the end…or if we get a draw.

(By the way, sanofi’s public announcement about the latest back and forth is here and Genzyme’s official take is here.)

Prince of Darkness and wife bring personal genomics issues to light

Last week, our senior editor, David Hutton, shared with you the news that rock star Ozzy Osbourne had his full genome sequence. Shortly after the Prince of Darkness revealed the results of his testing at the TEDMED conference in San Diego, his wife, Sharon Osbourne—a celebrity of her own right, between managing her husband’s career and her many television gigs—discussed the experience on her new talk show, “The Talk.”

“The Talk” is a daily talk/variety show co-hosted by Julie Chen, Sarah Gilbert, Holly Robinson Peete, Leah Remini and Marissa Jaret Winokur.

According to the Osbournes, the couple decided to allow Cofactor Genomics and Knome Inc. to sequence and analyze their DNA, respectively, because “they were looking for a celebrity to say, “OK, I don’t mind knowing what my medical life is going to be and I don’t mind sharing it with the world,” said Sharon to her co-hosts.

“Eventually—say, in 10 years, this invention will be in every doctor’s office, all over the world, where they take your blood, they analyze it, and they will tell you your complete medical path in life,” Sharon, who is a colon cancer survivor, said. “Everything, from your allergies, to your heart, to your brain, to how clever you are, to what you excel in. It’s such a leap, scientifically and medically, for all of us, that in 10 years, we’ll go into a doctor’s office and you’ll know if you have a cancer gene. You will know how to deal with it before it becomes an active cancer, or Alzheimer’s, or Parkinson’s.”

According to Sharon, among the insights Ozzy gained into his DNA were that he is allergic to coffee, has a “slight nerve disorder” as well as “the addictive gene” and is a” distant cousin” of TV talk show host and comedian Stephen Colbert. But Ozzy wasn’t exactly eager to hear the results, she said.

“He thought that it was, ‘where am I going to die,’ like someone was going to go to somebody and they were going to read his palm, like, ‘where am I going to go, so I never go into that place?'” Sharon said.

As David shared with you all last week, Ozzy has said that if genetic testing determines he has a risk of developing an untreatable disease such as Alzheimer’s, he’d rather not know about it. Ozzy’s tests came back negative in that regard, but Sharon is eagerly awaiting her results and hoping for the same outcome.

“The reasons I wanted to do it were because my father died of Alzheimer’s, and my mother’s mother died of Alzheimer’s, she said. “I want to know if I’m going to get it, so I can get my life in order.”

“I don’t know if I want to know,” said Sharon’s co-host, Peete, an actress and advocate for autism awareness and research. That’s the sentiment expressed by many folks since personal genetic testing became commercially available. We first reported on this debate in July 2009, when I interviewed 23andMe about a partnership the personal genomics company forged with PatientsLikeMe.com, an online patient community and platform for collecting and sharing patient data, on a large-scale genetic study of Parkinson’s disease. In an editorial column that month, I revealed that 23andMe was facing controversy because some view that patients may not be able to “handle” knowing more about their health, and that some doctors feel it’s not their responsibility to “explain” the outcome of these personal genetic tests to their patients.

In September, we also reported that some “direct-to-consumer” personal genetic testing providers are under federal scrutiny for alleged misleading test results, deceptive marketing and other questionable practices.

What about you? Do you want to know what sort of health problems your DNA has in store for you?

MIT is putting nature to work for pharma

All right, nature, get to work! You’re on academia’s clock now, and pharma’s in the future

That’s right, the Massachusetts Institute of Technology (MIT) in Cambridge, Mass., is appropriating some of Mother Nature’s children and putting them to work to produce drugs, finding ways to make at least one plant (periwinkle) and at least one microbe (E. coli) make oncology drugs, according to a pair of fall announcements.

The first announcement came in late September with word that MIT researchers and collaborators from Tufts University have now engineered E. coli bacteria to produce large quantities of a critical compound that is a precursor to the cancer drug Taxol, originally isolated from the bark of the Pacific yew tree. The tree’s bacteria can produce 1,000 times more of the precursor, known as taxadiene, than any other engineered microbial strain, and the new MIT technique could bring down the manufacturing costs of Taxol.

More than that, it could also help researchers discover potential new drugs for cancer and other diseases such as hypertension and Alzheimer’s, says Gregory Stephanopoulos, who led the team of MIT and Tufts researchers.

“If you can make Taxol a lot cheaper, that’s good, but what really gets people excited is the prospect of using our platform to discover other therapeutic compounds in an era of declining new pharmaceutical products and rapidly escalating costs for drug development,” says Stephanopoulos, the W.H. Dow Professor of Chemical Engineering at MIT.

Early November brought the second announcement, that researchers led by an MIT associate professor, Sarah O’Connor, have added bacterial genes to the periwinkle plant, enabling it to attach halogens such as chlorine or bromine to a class of compounds called alkaloids that the plant normally produces. Many alkaloids have pharmaceutical properties, and halogens, which are often added to antibiotics and other drugs, can make medicines more effective or last longer in the body, MIT reports.

The team’s primary target, an alkaloid called vinblastine, is commonly used to treat cancers such as Hodgkin’s lymphoma. O’Connor sees vinblastine and other drugs made by plants as scaffolds that she can modify in a variety of ways to enhance their effectiveness.

“We’re trying to use plant biosynthetic mechanisms to easily make a whole range of different iterations of natural products,” she says. “If you tweak the structure of natural products, very often you get different or improved biological and pharmacological activity.”

Although engineering new genes into plants is nothing new, O’Connor’s approach, known as metabolic engineering, goes beyond simply adding a gene that codes for a novel protein. As MIT described it, “Metabolic engineers tinker with the series of reactions that the host organisms use to build new molecules, adding genes for new enzymes that reshape these natural synthetic pathways. This can lead to a huge variety of end products.”

In future work, the researchers hope to engineer full periwinkle plants to produce the novel compounds. They are also working on improving the overall yield of the synthesis, which is about 15-fold lower than the plant’s yield of naturally occurring alkaloids.

With this much activity in two such disparate organisms, one can only imagine what MIT will put into service next. Maybe they can recruit some of those weeds in my garden to work for pharma so that they can do something more productive than rip my hands to shreds as I yank them up.