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#ChemCoach Carnival: From Big Pharma to Non-Profit

We’re almost at the end of National Chemistry week, folks, and the Haystack is finally kicking in to blogger SeeArrOh’s now rampant #ChemCoach carnival. The goal of any carnival is to get a lot of different bloggers to post on the same topic–in this case, to write about how they got to where they are today as a way of educating young chemists on their career options. Round-ups of the dozens of posts this week can be found here, here, and here. Since the science writing field has been well covered here and by our own Carmen Drahl, and because the Haystack is focused on all things pharma, I thought I’d enlist the help of someone with a much more illustrious career than my own. Without further ado, I give you some words of career wisdom from TB Alliance‘s chemistry guru Christopher Cooper:

Your current job.
 
I’m Senior Director of Chemistry at the Global Alliance for TB Drug Development (TB Alliance), a non-profit, product development partnership headquartered in New York City.  My job encompasses all chemistry activities for the Alliance from early-, mid-, and late-stage drug discovery right through drug substance/API manufacturing for clinical trials.  The TB Alliance is dedicated to identifying safe, novel chemical entities for the rapid treatment of tuberculosis worldwide, and my job is to oversee the Alliance’s chemistry needs to achieve our goals (seewww.tballiance.org for more details).


What you do in a standard “work day.”
 
Define “standard” … oh, and define “work day,” as well, please? All kidding aside, working for a small (~45 employees), entrepreneurial, research and development organization means that every day is truly different, whether it’s engaged in project team discussions with collaborators in Chicago and Belgium, or proposing new analogues/chemical series to pursue with chemists in Auckland or Seoul!  In fact, as we engage chemists (medicinal, process, manufacturing) on TB Alliance projects around the globe, my work “day” doesn’t really begin or end.  After all, if it’s 9:00 P.M. on the East Coast, it’s already 9:00 A.M. in Beijing!  Fortunately, the virtual nature of our business model translates into my own flexibility in addressing issues wherever and whenever they occur … and I don’t have to wash my glassware anymore (yey!).


What kind of schooling / training / experience helped you get there?
 
In many ways, my background would appear fairly conventional, despite the more unconventional nature of my current position.  I received my B.S. from Clemson University in 1980, and my M.S. (1982) and Ph.D.’s (1988) from Stanford.  Having worked briefly in the pharmaceutical industry (CIBA-Geigy from 1982-1984), I was eager to return so I accepted a position at Pfizer Central Research in 1988.  From 1988 to 1998, I enjoyed a varied career at PFE, working in both veterinary medicine and “conventional” human drug discovery.  I was also a strong proponent/practitioner of combinatorial chemistry, and solution-phase array approaches for the rapid interrogation of lead chemical series and the development of program-specific SAR/SLR. This interest in combichem provided me with an opportunity to “take a risk” and join Bristol-Myers Squibb in 1998, in a newly created position within their Early Discovery Chemistry department.  As head of the Lead Synthesis group, our small, dedicated team of chemists helped to shape the BMS corporate screening collection, and, more importantly, to rapidly “explode” attractive hit series for a host of therapeutic targets.  In late 2008, I was approached about “taking a risk” with another newly created position, this time working with a small, dedicated team of seasoned drug hunters striving to find safe and effective cures for an infectious disease which kills one person every 20 seconds.  I had no idea what I was getting myself in for … but having now been at the TB Alliance for just under 4 years, I see this as one of my greatest life adventures (… thus far)!  So, what helped me get here? I suppose it was a mix of hard work, personal energy, a bit of risk taking, and scientific – not just chemistry – curiosity which helped provide me with the breadth of experiences necessary for tackling the breadth of challenges I face every day.  

How does chemistry inform your work?
 
Without hyperbole, chemistry is truly the lifeblood of our efforts to identify novel, safe, and effective treatments for tuberculosis.  Consider the following: the youngest component of the standard four drug regimen for drug-sensitive TB (e.g., rifampin, pyrazinamide, isoniazid, and ethambutol) will celebrate its 50th “birthday” in 2013.  That’s fifty years old.  This is completely unacceptable.  Wehave to change this, and we ARE changing this, and we are changing this through the use of 21stcentury chemistry approaches to both optimize antimicrobial chemical series, and to produce such materials safely and efficiently on large scale.  Whether I’m challenged with scaffold “hopping” to a new lead series, or looking to decrease the cost of goods (COG’s) for a 120 kg GMP API campaign, chemistry remains front and center.

Finally, a unique, interesting, or funny anecdote about your career*
 
About two years’ ago, I was on a business trip with the TB Alliance in northern France.  Our hosts graciously invited us to visit the famous cathedral city of Rouen for a bit of site-seeing before dinner.  While crossing one cobblestoned street intersection, I heard someone call my name from behind.  It turned out to be an old friend and fellow chemistry colleague from Stanford whom I had not seen in ~25 years!! The moral of the story is to make, develop, and appreciate the chemistry friendships which you “acquire” over time – it is truly a small (chemistry) world, after all!

BMS Cuts R&D Jobs

The ax is falling on more pharma R&D jobs. Earlier today, Derek Lowe brought word from readers that research jobs were being cut at Bristol-Myers Squibb. The company just confirmed that “fewer than 100″ positions were being eliminated in the U.S. Here’s the official word from BMS:

“Bristol-Myers Squibb is strategically evolving the company’s Research focus to ensure the delivery of a sustainable, innovative drug pipeline in areas of serious unmet medical need and potential commercial growth.
The Company is aligning and building internal capabilities to support the evolution of its Research focus. In doing so, certain research areas will be streamlined and there will be investment and growth in other areas. This strategic evolution has resulted in job eliminations in the short term to allow longer term investment. This initiative will result in a reduction in employee headcount of fewer than 100 people in an R&D organization of more than 7,000 employees. Impacted employees were notified on August 1, 2012 and transitions will take place within two weeks of this date.”

The company will not confirm whether they are, as Derek’s sources suggest, in the metabolic disease area or limited to New Jersey. If indeed they are all coming out of its N.J. labs, today’s announcement will add to challenging times for the state.  As we wrote last month after Roche announced plans to shutter its Nutley site, costing some 1,000 jobs, the number of drug industry jobs in N.J. fell by 22.4% between 2007 to 2010, according to a report by Battelle and the Biotechnology Industry Organization.

AstraZeneca to Shed 2,200 R&D Jobs

AstraZeneca wielded a heavy ax to its workforce today as it prepares for tougher times ahead. The British-Swedish drugmaker is chopping 7,300 jobs, including 2,200 R&D positions, in hopes of achieving $1.6 billion in annual cost savings by 2014.

This is the third round of major cutbacks at AstraZeneca. In 2010, the company announced plans to slash 8,000 jobs over four years, a move that added to the elimination of 15,000 jobs between 2007 and 2009. This specific round girds against an onslaught of generic competition for key products and accounts for several disappointments in the company’s late-stage pipeline. In the coming months, the company will lose patent protection in various markets for the anti-psychotic Seroquel IR, the anti-cholesterol drug Crestor, and the blood thinner Atacand. Meanwhile, AstraZeneca’s late-stage pipeline has faltered. The recent setbacks (adding to earlier ones) include ending development of the PARP inhibitor olaparib, which prompted it to take a $285 million charge; a failed Phase III trial for the antidepressant TC-5214; and a thumbs down from FDA last month for dapagliflozin, a Type II diabetes drug being developed with Bristol-Myers Squibb.

R&D has taken a heavy hit in each round of cuts. During the Q&A session following AstraZeneca’s earnings presentation, one analyst said his back of the envelope calculations suggest the company will have shed 7,600 R&D jobs between 2006 and 2014. Based on comments by AstraZeneca’s R&D chief Martin Mackay, small molecule research has born the brunt of those cuts. He noted that headcount in biologics research has grown, and pointed out that biologics now account for 40% of the company’s early-stage pipeline (candidates in studies earlier than Phase II), up from 15-20% in recent years.

The latest R&D revamp will be primarily focused on AstraZeneca’s neuroscience activities, where the risk of investment is seen as particularly high. “It’s a really tough area,” Mackay said.  “The industry hasn’t produced enough and we haven’t produced enough.”

The challenge was highlighted in November, when TC-5214, an anti-depressant being developed by Targacept and AstraZeneca, failed to show benefit in a Phase III trial. The bad news came as a surprise, as TC-5214 had demonstrated strong efficacy in smaller trials. Three other Phase III trials are underway, but analysts are skeptical that the program can be salvaged. “Prospects appear grim,” Leerink Swann analyst Joshua Schimmer said in a note last month.

AstraZeneca is creating a small team of 40 to 50 scientists that will work with external partners in academia and industry to discover and develop neuroscience drugs. The adoption of this new strategy means that the company’s Montreal R&D facility will be shuttered, and it will end R&D at its Södertälje site in Sweden.

AstraZeneca’s overhaul of its neuroscience activities is the latest in what appears to be a big pharma exodus from internal central nervous system R&D. In December, Novartis said it would close its neuroscience research facility in Basel, Switzerland, and GlaxoSmithKline two years ago decided to end research in certain central nervous system areas, such as depression and pain.

Genzyme R&D Layoffs Today

The other shoe has dropped at Genzyme, which last year was acquired by Sanofi, but had yet to experience the kind of major research restructuring that typically accompanies the integration of two pharma companies. Today, Genzyme scientists were told whether their job was being shed or moved. Here’s an excerpt from the official statement:

As part of the integration process between Sanofi and Genzyme, R&D activities were reviewed and assessed. On January 31, 2012, the results of the review of U.S. R&D Genzyme activities were announced, including synergies that unfortunately make some positions redundant. All US R&D Genzyme employees impacted by the integration received notice regarding whether their position would be relocated or eliminated.

The job cuts are separate from the latest round of R&D layoffs at Sanofi. As readers might recall, Sanofi announced last November that it was closing its Bridgewater R&D site, and move discovery and early development activities to Boston. A Sanofi spokesperson tells the Haystack that despite today’s cuts at Genzyme, the company is committed to its presence in Massachusetts, and to maintaining a stable level of jobs there. While R&D is falling under the axe, the company is hiring in manufacturing and multiple sclerosis, she says.

The company has not provided details on how many R&D scientists will be shed, but once more information comes to light, we’ll update readers.

Haystack 2011 Year-in-Review

Well, 2011 is in the books, and we here at The Haystack felt nostalgic for all the great chemistry coverage over this past year, both here and farther afield. Let’s hit the high points:

1. HCV Takes Off – New treatments for Hepatitis C have really gained momentum. An amazing race has broken out to bring orally available, non-interferon therapies to market. In October, we saw Roche acquire Anadys for setrobuvir, and then watched Pharmasset’s success with PSI-7977 prompt Gilead’s $11 billion November buyout.  And both these deals came hot on the heels of Merck and Vertex each garnering FDA approval for Victrelis and Incivek, respectively, late last spring.

2. Employment Outlook: Mixed – The Haystack brought bad employment tidings a few times in 2011, as Lisa reported. The “patent cliff” faced by blockbuster drugs, combined with relatively sparse pharma pipelines, had companies tightening their belts more than normal. Traffic also increased for Chemjobber Daily Pump Trap updates, which cover current job openings for chemists of all stripes. The highlight, though, might be his Layoff Project.  He collects oral histories from those who’ve lost their jobs over the past few years due to the pervasive recession and (slowly) recovering US economy.. The result is a touching, direct, and sometimes painful collection of stories from scientists trying to reconstruct their careers, enduring salary cuts, moves, and emotional battles just to get back to work.

3. For Cancer, Targeted Therapies – It’s also been quite a year for targeted cancer drugs. A small subset of myeloma patients (those with a rare mutation) gained hope from vemurafenib approval. This molecule, developed initially by Plexxikon and later by Roche / Daiichi Sankyo, represents the first success of fragment-based lead discovery, where a chunk of the core structure is built up into a drug with help from computer screening.From Ariad’s promising  ponatinib P2 data for chronic myeloid leukemia, to Novartis’s Afinitor working in combination with aromasin to combat resistant breast cancer. Lisa became ‘xcited for Xalkori, a protein-driven lung cancer therapeutic from Pfizer. Researchers at Stanford Medical School used GLUT1 inhibitors to starve renal carcinomas of precious glucose, Genentech pushed ahead MEK-P31K inhibitor combinations for resistant tumors, and Incyte’s new drug Jakifi (ruxolitinib), a Janus kinase inhibitor, gave hope to those suffering from the rare blood cancer myelofibrosis.

4. Sirtuins, and “Stuff I Won’t Work With  – Over at In the Pipeline, Derek continued to chase high-profile pharma stories. We wanted to especially mention his Sirtris / GSK coverage (we had touched on this issue in Dec 2010). He kept up with the “sirtuin saga” throughout 2011, from trouble with duplicating life extension in model organisms to the Science wrap-up at years’ end. Derek also left us with a tantalizing tidbit for 2012 – the long-awaited “Things I Won’t Work With” book may finally be coming out!

5. Active Antibacterial Development – In the middle of 2011, several high-profile and deadly bacterial infections (Germany, Colorado, among others) shined a spotlight on those companies developing novel antibacterials. We explored front -line antibiotics for nasty Gram-negative E.coli, saw FDA approval for Optimer’s new drug Fidiclir (fidaxomicin) show promise against C. difficile  and watched Anacor’s boron-based therapeutics advance into clinical testing for acne, and a multi-year BARDA grant awarded to GSK and Anacor to develop antibacterials against bioterrorism microorganisms like Y. pestis.

6. Obesity, Diabetes, and IBS – Drugs for metabolic disorders have been well-represented in Haystack coverage since 2010. Both Carmen and See Arr Oh explored the vagaries of Zafgen’s ZGN-433 structure, as the Contrave failure threatened to sink obesity drug development around the industry. Diabetes drugs tackled some novel mechanisms and moved a lot of therapies forward, such as Pfizer’s SGLT2 inhibitors, and Takeda’s pancreatic GPCR agonist. Ironwood and Forest, meanwhile, scored an NDA for their macrocyclic peptide drug, linaclotide.

7. The Medicine Show: Pharma’s Creativity Conundrum – In this piece from October, after Steve Jobs’ passing, Forbes columnist Matt Herper both eulogizes Jobs and confronts a real ideological break between computer designers and drug developers. His emphasis? In biology and medical fields, “magical thinking” does not always fix situations as it might in computer development.

We hope you’ve enjoyed wading through the dense forest of drug development with Carmen, Aaron, Lisa, and See Arr Oh this past year. We here at The Haystack wish you a prosperous and healthy 2012, and we invite you to come back for more posts in the New Year!

Pfizer: No Sacred Cows in R&D

Just when we thought it was over, the cost-cutting at Pfizer continues. In tandem with this morning’s fourth-quarter earnings announcement, Pfizer said it was closing its R&D site in Sandwich, U.K., and paring back research in Groton, Conn., both sites that had survived earlier cutbacks relatively unscathed. Upwards of 3,500 jobs are at risk in the cutbacks. First some details, and then some thoughts on what the new Pfizer research might shape up as.

The details:

–The closure of the Sandwich site will impact 2,400 jobs, although Pfizer says as the shutdown happens over the next 18-24 months, it hopes to move a few hundred folks over to other sites or to external partners.

–Some 25% of the 4,400 employees at Pfizer’s Groton and New London campuses will be shed.

–Internal research will be focused on a few core areas:  neuroscience, cardiovascular, metabolic and endocrine, inflammation and immunology, oncology, and vaccines.

–Pfizer is creating dedicated units focused on pain and sensory disorders, biosimilars, and Asia R&D.

–Pfizer is exiting research in multiple areas: allergy and respiratory, located in Sandwich, U.K.; internal medicine, which includes some research in lung, kidney, and genital urinary diseases, also located in Sandwich; oligonucleotides and tissue repair, in Cambridge, Mass.; and antibacterials, situated in Groton.

–Regenerative medicine research in Cambridge, Mass., is also being dumped. However, similar work in Cambridge, U.K., will be part of a new pain and sensory disorder research unit.

–The R&D budget for 2012 will shrink. The company previously expected to spend $8-$8.5 billion on research next year; now, it will shell out nearly 20% less, or between $6.5 and $7 billion. Remember back to 2008 and 2009, when R&D spending topped $10 billion?

–Pfizer will establish external relationships for several activities, including manufacturing of active pharmaceutical ingredients and dosage forms, toxicology, and bioanalytics.

–Pfizer is aligning its R&D network around a few hubs: Cambridge, Mass., San Francisco, New York, LaJolla, and Cambridge, U.K.

As for the new “innovation engine” at Pfizer, CEO Ian Read today told investors he would be working closely with R&D chief Mikael Dolsten to overhaul the research culture at Pfizer. The idea is to empower research units with the decision making and also hold them accountable for the outcomes. Or as he put it, give scientists a feeling of “owning the money and owning the results.” This strategy sounds a lot like one that’s been taking shape over the last two years at GlaxoSmithKline and, more recently, at AstraZeneca. One analyst asked whether the research programs falling to the ax will be spun out into biotechs. The possibility seemed real, and it again sounded a lot like the kind of de-risking approach GSK is using with its external discovery unit, which has started up several small companies out of clusters of assets.

Another question is what will happen with that Sandwich site. It’s worth noting that some of Pfizer’s critical small molecule discoveries happened at that site. Viagra, Norvasc, and Diflucan are among the inventions to come out of Sandwich.

There was a lot of talk on today’s call about external partnerships, and one has to wonder whether Pfizer will go the way of Lilly, Sanofi, and GSK. Recall that those companies have all sold major R&D sites to contract research organizations (Lilly/Covance, Sanofi/Covance, and GSK/Aptuit), but signed a long-term contract for services out of the sites they had just shed. Readers, any guesses on what will happen with that site?

Another Week in Pharma Job Cuts

This week brought a stream of bad news on the pharma job front, with at least four companies announcing substantial cutbacks. Worse, scientists were the main target for layoffs at three of those companies—Sanofi-Aventis, Arena, and Elan. As everyone’s favorite employment watchdog Chemjobber commented on an In the Pipeline post about cuts at Abbott: When, when, when will it stop? Here’s a look back at the news from this week:

–Sanofi is shedding 90 research jobs at its Bridgewater, N.J., site as part of “the evolution of the R&D portfolio towards more biologic-based therapies,” the company told C&EN. The French pharma firm is ceasing chemical library and chemical development activities, including pharmaceutical development and analytical science. Meanwhile, discovery-stage laboratory activities within several groups, including Lead Identification Technologies, Structure, Design & Informatics, and Analytical Sciences, will be reduced.

Some people will be shifted over to the company’s Molecular Innovative Therapeutics group, which will be transformed into “a cluster of small multidisciplinary biotechs with specialized expertise in key diverse therapeutic approaches.” This new approach sounds an awful lot like what GlaxoSmithKline has been doing over the last two years—creating smaller, more independent units in the hopes of mimicking the culture and innovative spirit of small biotechs.

–Arena Pharmaceuticals is cutting 25% of its staff, or 66 employees, by the end of March. The move isn’t unexpected. Last fall, FDA gave the San Diego-based biotech a thumbs down for its obesity drug lorcaserin based on concerns that it had caused tumors in rats. Now, FDA is asking for a slew of new data, meaning Arena will be unlikely to refile its application for approval until 2012, analysts say. See here and here for more on its lorcaserin trials and tribulations.

–Abbott is slashing 1,900 jobs in the U.S., mirroring layoffs it made last year in Europe following its acquisition of Solvay Pharmaceuticals. The cuts will come from its commercial and manufacturing operations, with over half the job losses concentrated in Northern Illinois. In a conference call, Abbott CEO Miles D. White blamed the restructuring on several factors: the slow recovery of the global economy, costs associated with healthcare reform, European pricing pressures, and a harsher regulatory environment that has made it tough for drugs to get approved.

–And last but not least, Elan has laid off 10% of its staff, or about 130 workers, with its R&D site in South San Francisco most heavily impacted. Researchers accounted for about half of the job losses.

If we’ve missed any layoffs that chemists should be aware of, drop us a note or leave a comment.

Haystack 2010 Year-In-Review

This Friday, we’re looking back at 2010′s big news in pharma and biotech, both the good and the bad. Check out our picks and be sure to weigh in on what you think we missed.

1. Provenge Approved

In April, Dendreon’s Provenge became the first approved cancer immunotherapy. Dendreon CEO Mitch Gold called it “the dawn of an entirely new era in medicine.” And while prostate cancer patients are excited for a new treatment option, the approval is perhaps most exciting for its potential to reignite interest in cancer immunotherapy research. There’s a lot of room for improving the approach—Provenge is, after all, expensive and highly individualized. Now that immunotherapy have been proven to work, there’s hope that the lessons learned in both its discovery and clinical development will aid scientists in inventing even better cancer vaccines.

2. Obesity Field Slims

The obesity drug race played out in dramatic fashion in 2010, with three biotech companies-Vivus, Arena, and Orexigen, each making their case for its weight-loss medication before FDA. As of this writing, Orexigen’s drug Contrave seems to be on the surest footing to approval, but longtime obesity-drug watchers know that caution seems to rule the day at FDA, so nothing is a sure bet.

Orexigen’s Contrave and Vivus’s Qnexa are both combinations of already-approved drugs, whereas Arena’s Lorqess is a completely new molecule. When C&EN covered the obesity race in 2009, it seemed that Lorqess (then going by the non-brand-name lorcaserin) had the cleanest safety profile, but Qnexa was best at helping patients lose weight.

But FDA’s panels didn’t always play out the way folks expected. There were safety surprises- notably the worries about tumors that cropped up in rats on high doses of Lorqess, and the extensive questioning about birth defect risks from one of the ingredients in Vivus’ Qnexa. The fact that FDA’s panel voted favorably for Orexigen’s Contrave, a drug that’s thought to have some cardiovascular risks, generated discussion because FDA pulled Abbott’s Meridia, a diet drug with cardiovascular risks, from the market in October.

The dust still hasn’t fully settled. Arena and Vivus received Complete Response Letters from FDA for Lorqess and Qnexa. Vivus has submitted additional documentation and a followup FDA meeting on Qnexa is happening in January. Also to come in January is the agency’s formal decision on Contrave. And if you’re interested in learning about the next wave of obesity drugs coming up in clinical trials, read this story in Nature News.

3. Sanofi & Genzyme: The Neverending Story

Speaking of drama, Sanofi’s pursuit of Genzyme has been in the headlines for months now, and promises to stretch well into 2011. The story goes something like this: Genzyme had a tumultuous year, as it struggled to correct the manufacturing issues that created product shortages and eventually led to a consent decree with FDA. In walked Sanofi, who offered—in a friendly way—to buy the company for $18.5 billion. Genzyme refused to consider what it viewed as a lowball offer. Weeks passed, they remained far apart on price with no signs of anyone budging, until Sanofi finally went hostile. Genzyme suggested it would be open to an option-based deal, which would provide more money later on if its multiple sclerosis drug candidate alemtuzumab reached certain milestones. Sanofi stuck to its $18.5 billion guns and is now trying to extend the time period to convince shareholders to consider its offer.

4. Final Stretch in HCV Race

This year, the industry finally got a peek at late-stage data for what are likely be the first drugs approved for Hepatitis C in more than two decades. Based on Phase III data, analysts think Vertex’s telaprevir will have an edge over Merck’s boceprevir once the drugs hit the market. Meanwhile, the next generation of HCV drugs had a bumpier year, with several setbacks in the clinic. Still, the flood of development in HCV has everyone hoping that eventually people with HCV can take a cocktail of pills, rather than the current harsh combination of interferon and ribavirin.

5. Pharma Covets Rare Diseases

Historically, research in rare diseases has been relegated to the labs of small biotechs and universities. But in 2010, big pharma firms suddenly noticed that if taken in aggregate, a pretty sizable chunk of the public—on the order of 6%–suffer from rare diseases. They also noticed that when there’s a clear genetic culprit, drug discovery is a bit more straightforward. Further, rare disease can sometimes be a gateway to approval in larger indications, making them all the more appealing. With that, Pfizer and GlaxoSmithKline both launched rare diseases units and made a series of acquisitions and licensing deals (Pfizer/FoldRxGSK/AmicusGSK/Isis, etc) to accelerate their move into the space. Meanwhile, Sanofi is trying to jump in with both feet through its proposed acquisition of Genzyme.

6. MS Pill Approved

Novartis gained approval in September for Gilenya, the first treatment for multiple sclerosis that is a pill rather than an injection. In even better news for people with MS, there more pills are rounding the corner towards FDA approval: Sanofi’s teriflunomide, Teva’s laquinimod, and Biogen’s BG-12. All of these drugs come with safety caveats, but the idea of new treatment options after years depending on interferons has gotten everyone in the MS field pretty excited.

7. Antibody-Drug Conjugates Prove Their Mettle

The concept of linking a powerful chemo drug to a targeted antibody, thereby creating something of a heat-seeking missile to blast tumor cells, isn’t new. But antibody-drug conjugate technology has finally matured to a point where it seems to be, well, working. Seattle Genetics presented very positive results from mid-stage studies of SGN-35 in two kinds of lymphoma. And ImmunoGen provided clear data showing its drug T-DM1 could significantly minimize side effects while taking down breast cancer.

8. Pharma Forges Further into Academia

With nearly every pharma firm paring back internal research, the focus on external partnerships has never been greater. Broad deals with universities are becoming more common, and Pfizer has arguably gone the furthest to evolve the model for working with academic partners. In May, Pfizer announced a pact with Washington University under which the academic scientists will look for new uses for Pfizer drug candidates. As part of the deal, they gain unprecedented access to detailed information on Pfizer’s compound library. And last month, Pfizer unveiled the Center of Therapeutic Innovation, a network of academic partnerships intended to bridge the “valley of death,” between early discovery work and clinical trials. The first partner is University of California, San Francisco, which scores $85 million in funding over five years, and the network will eventually be comprised of seven or eight partners, worldwide. Most notable is that Pfizer is planting a lab with a few dozen researchers adjacent to the UCSF campus to facilitate the scientific exchange.

9. Finally, New Blood Thinners

This year saw the FDA approval of a viable alternative to coumadin (aka warfarin), a 50-plus-year-old workhorse blood thinner that interacts with many foods and herbal supplements.

Boehringer’s Pradaxa (dabigatran) got a unanimous thumbs-up from an FDA panel for preventing stroke in patients with a common abnormal heart rhythm called atrial fibrillation. FDA approved the drug in October. The next new warfarin alternative to be approved could be Xarelto (rivaroxaban), which has had favorable results in recent Phase III clinical trials, as David Kroll over at Terra Sig explained. Both Xarelto and Pradaxa had already been approved for short term use outside the US.

Rivaroxaban and dabigatran work at different stages of the biochemical cascade that leads to clotting, as we illustrated here. Another drug candidate in the warfarin-alternative pipeline is BMS’s and Pfizer’s apixaban. Check out coverage of apixaban trials here and at Terra Sig. And in a separate blood-thinner class, FDA today rejected Brilinta, a possible competitor to mega-blockbuster Plavix.

10. Alzheimer’s Progress & Setbacks

Alzheimer’s disease has been a tough nut to crack, and news in 2010 has done little to dispel this reputation. This year Medivation’s Dimebon, which started life as a Russian antihistamine and showed some promise against Alzheimer’s, tanked in its first late-stage clinical trial. Later in the year, Eli Lilly halted development of semagacestat after the compound actually worsened cognition in Alzheimer’s patients. Semagacestat targeted the enzyme gamma-secretase, and the New York Times and other outlets reported the news as shaking confidence into a major hypothesis about what causes Alzheimer’s and how to treat it– the amyloid hypothesis.

But not everyone agreed with that assertion. Take Nobel Laureate Paul Greengard, who told C&EN this year (subscription link) that semagacestat’s troubles may have been due to the drug’s incomplete selectivity for gamma-secretase.

This year Greengard’s team discovered a potential way to sidestep the selectivity issue, by targeting a protein that switches on gamma-secretase and steers it away from activities that can lead to side effects. Greengard thinks the amyloid hypothesis is very much alive. But the final word on the amyloid hypothesis will come from trial results in next year and beyond, for drugs such as BMS-708163, Bristol Myers Squibb’s gamma-secretase inhibitor.

11. Avandia (Barely) Hangs On

Avandia was once the top selling diabetes medication in the world, but in 2010 long-running rumblings about the drug’s cardiovascular risks reached fever pitch. By the fall, Avandia was withdrawn from the European Union market and heavily restricted in the US.

Avandia (rosiglitazone) helps diabetics control their blood sugar levels by making cells more responsive to insulin. Widespread scrutiny of Avandia dates back to 2007, when a study led by Vioxx-whistleblower and Cleveland Clinic cardiologist Steve Nissen suggested Avandia increased the risk of heart attacks. In February 2010, a leaked government report that recommended Avandia be pulled from the market made headlines. In July, an FDA advisory panel voted on what to do about Avandia, and the results were a mixed bag, with most panel members voting either to pull the drug entirely or add severe restrictions. In the end, FDA sided with the “restrict” panelists- Avandia is still on the market, but it can only be prescribed to patients who can’t control their blood sugar with a first-line medication.

Clearly, researchers still have a lot to learn about how the drugs in Avandia’s class work. But we enjoyed reading Derek Lowe’s self-characterized rant about just how much effort has been put in so far. Among several other drugs in Avandia’s class, Rezulin (troglitazone) was pulled from the market many years ago because of adverse effects on the liver, but Actos (pioglitazone) remains on the market and appears to be safe.

12. Executive Musical Chairs

The year after a trio of mega-mergers and at a time when patent losses are piling up, drug companies shook up their management. The most notable changes came at Pfizer: First, the company abandoned its two-headed approach to R&D leadership and picked Michael Dolsten, former head of R&D at Wyeth, to lead research. Martin Mackay, Pfizer’s head of R&D, meanwhile jumped ship to lead R&D at AstraZeneca. Then, in a move that took everyone by surprise, Pfizer’s CEO Jeff Kindler suddenly stepped down and Ian Reade took over. At, Merck, president Kenneth Frazier will take over as CEO in January;  Richard T. Clark will stay on as chairman of Merck’s board. And just this week, Sanofi-Aventis saidformer NIH director Elias Zerhouni would replace Marc Cluzel as head of R&D, while Merck KGaA appointed Stefan Oschmann as head of pharmaceuticals. Oschmann comes on from Merck & Co., where he was president of emerging markets.

In the biotech world, the most notable shift came in June, when George Scangos moved over from leading Exelixis totake the top job at Biogen Idec.

13. RNAi Rollercoaster

The year has been a tumultuous one for RNAi technology. Leaders in siRNA technology are experiencing growing pains as they try to turn promising science into commercialized products. Alnylam, arguably the best-known and biggest player in the RNAi arena, laid off 25% of its staff after Novartis decided not to extend its pact with Alnylam. Things only got worse when Roche announced it was exiting RNAi research, a move that hit its development partners Alnylam and Tekmira. Roche seemed to be primarily worried about delivery, an issue that is holding the field back from putting more RNAi-based therapeutics into the clinic.

But it’s not all bad news: the year brought a spate of big-ticket deals for companies developing other kinds of RNAi technology. GSK signed on to use Isis Pharmaceuticals’ antisense technology, which uses single-stranded rather than double-stranded oligonucleotides. And Sanofi entered into a pact with Regulus, the microRNA joint venture between Isis and Alnylam, worth $740 million. Further, Isis and Genzyme made some progress with mipomersen, the cholesterol drug developed using Isis’ antisense technology.

14. Revival of Interest in Cancer Metabolism

In cancer research, the old was new again in 2010, with a flurry of publications about depriving cancer cells of their energy source by taking advantage of quirks in their metabolism. That idea has been around since the 1920′s- when German biochemist Otto Warburg noticed differences in how cancer cells and normal cells deal with glucose. This year, Celgene handed over $130 million upfront for access to any cancer drugs that come out of Massachusetts biotech Agios Pharmaceuticals’ labs. One target in Agios’s crosshairs is an enzyme involved in glucose metabolism- pyruvate kinase M2. In addition to the Celgene/Agios deal, we noted that AstraZeneca and Cancer Research UK are in a three-year pact related to cancer metabolism, and the technology behind GlaxoSmithKline’s much-talked-about $720 million purchase of Sirtris has to do with depriving cells of energy.

15. More Job Cuts

Not to end this list on a sour note, but it wouldn’t be complete without acknowledging the ongoing narrative of layoffs and retooling at drug companies. This year brought brutal cuts at AstraZeneca, GSK, Bristol-Myers Squibb, and Abbott, along with the widespread and ongoing layoffs at Pfizer and Merck. Several features in C&EN looked at the impact the cuts are having on chemists:

How some laid-off pharma chemists migrate to new careers

How academic programs are adapting

And the views from the ground in New England and California, two hotbeds of pharma/biotech (hint- it ain’t pretty).

For more jobs insight, join the discussions happening with Chemjobber and Leigh aka Electron Pusher, and check out their chemistry jobs blog roundtable, which just wrapped today.

This Week in Pharma Job Cuts…

As we know, its tough out there for scientists working in the pharmaceutical and biotech industries. This week brought yet another spate of drug industry cutbacks that seemed worth chronicling. For those keeping track:

Abbott Laboratories is getting rid of 3% of its workforce, or about 3,000 jobs, as it folds Solvay’s pharmaceuticals business into its operations. Most of the cuts will come from Europe: 300 jobs will be trimmed in Hannover, Germany; 500 in Weesp, the Netherlands; and Solvay’s U.S. headquarters in Marietta, Ga., will be shuttered. According to SEC filings, certain R&D programs will be discontinued (perhaps they can be auctioned off?).

Alnylam Pharmaceuticals, a leader in RNAi technology, is shedding 25-30% of its employees after Novartis decided not to opt-in to a technology licensing clause worth $100 million at the end of a five-year pact between the companies. The biotech raked in $125 million in funding during the lifetime of the pact, and had 25 full-time employees working on projects for Novartis. An interesting tidbit from a conference call held this morning from Alnylam: According to Alnylam’s CEO John Maraganore, Novartis now has 100 people working on RNAi technology at its site in Cambridge, Mass. Clearly they made a commitment to the field with their five-year pact with Alnylam, but somehow the sheer numbers were surprising. Alnylam expects to end the year with $320 million in cash on hand.

Bristol-Myers Squibb is cutting 3% of its workforce, estimated at around 800 jobs, as generic competition on its blood thinner Plavix looms. The company had already unveiled plans in 2008 to eliminate about 10% of its workforce, or about 3,700 jobs, by the end of this year. A 2007 cost-savings program had separately targeted 4,350 jobs.

Genzyme said last week it would eliminate 1,000 jobs over the next 15 months as it tries to right its manufacturing operations and combat takeover attempts.

Lundbeck is shedding 50 R&D jobs amid a reorganization of its R&D operations in Denmark and the U.S. The specialty pharma firm is shifting its focus to three main areas of biology– neurodegeneration, neuroinflammation and synaptic transmission—related to brain diseases, and will rely more on external partnerships.

Merck, meanwhile, appears to be having a tough time making cuts in the Netherlands, where it is essentially ridding itself of Organon’s R&D operations. According to Radio Netherlands, the big pharma firm is now negotiating with the Dutch government over the thousands of jobs slated to be lost in the region.

Scientists On The Move

I like taking the time to read the fine print in journal articles. When I first read the antibiotic work I posted about yesterday, I noticed that a few of the authors on the paper had little crosses next to their names. If you go to said fine print, you will find that they are no longer at GSK, but are located elsewhere. I’m no Chemjobber or Electron Pusher, but I try to pay attention to researchers’ moves.

Drake S. Eggleston, Fabrice Gorrec, Earl W. May & Alexandre Wohlkonig
Present addresses: Innovalyst, 1000 Centre Green Way, Suite 200, Cary, North Carolina 27513, USA (D.S.E.); MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK (F.G.); OSI Pharmaceuticals, 1 Bioscience Park Drive, Farmingdale, New York 11735, USA (E.W.M.); Vrije Universiteit Brussel, VIB Department of Molecular and Cellular Interactions, Pleinlaan 2, 1050 Brussels, Belgium (A.W.).