Posts Tagged → PFE
The evolution of the model for academic-pharma collaboration has been a topic of much discussion as more companies try to tap into university talent for early-stage research (recent examples of collaborations can be found here and here). Industry observers question whether anything tangible will come out of the efforts (see here for a recent critique), believing the divergent missions and cultural differences of each organization inevitably sidelines these pacts.
Pfizer is making one of the more aggressive pushes through its Centers for Therapeutic Innovation. Under the CTI model, Pfizer has set up labs in research hotbeds like Boston and San Francisco, where, through partnerships with various academic institutions, its scientists work side-by-side with university scientists to discover new biologics-based drugs. This week at BIO, I sat down with Tony Coyle, CTI’s chief scientific officer, to talk about CTI’s progress. A more in-depth look at the CTI model will come in the pages of the magazine, but in the meantime, I wanted to share some facts and figures that came out of our chat:
Number of CTIs formed: Four (San Francisco, San Diego, New York, Boston)
Number of academic centers involved: 20
Number of Pfizer scientists across each of its dedicated labs: roughly 100 (Coyle says about 75% were hired from the outside, coming from biotech, academia, with a few from big pharma)
Number of proposals reviewed in the last year: 400
Percentage of proposals overlapping with internal Pfizer efforts: <5%
Number of proposals funded so far: 23
Number of therapeutic areas being studied: 4 (rare diseases, inflammation, cardiovascular disease, and oncology)
Facts and figures aside, Pfizer is trying to move as quickly as possible given the learning curve of teaming with academia. Coyle said he’s promised his bosses that by the third year of the effort, at least four drugs will be in human studies across multiple therapeutic areas. “We’re well on our way to identifying a number of candidates, and I have no doubt that in the next 18 months, we’ll be in our first patient studies,” he added.
Those numbers could change in 2013, when Pfizer potentially expands its CTI outside the U.S. “Ex-U.S is still our ambition,” Coyle says. “2012 has been a period of ‘lets build the group, get the programs and start executing on the pipeline.’ For 2013, we will be and are looking at opportunities ex-U.S., and have had some pretty good discussions to date externally.”
In this week’s issue, I look at the perceived exodus by pharma companies from neuroscience R&D. Between AstraZeneca’s recent cutbacks, the closure of Novartis’ neuroscience research facility in Basel, and earlier moves by GSK and Merck, industry watchers are understandably worried that the neuroscience pipeline will dry up.
One person who isn’t worried is Michael Ehlers, Pfizer’s chief scientific officer for neuroscience research. Ehlers came to Pfizer a year and a half ago from Duke, with the explicit mission to revamp how the company finds and develops drugs for brain diseases. The scientist is convinced that the field is ripe for new and better drugs, and that by staying in the game, Pfizer will be in a good position to capitalize on what he believes will be a healthy flow of new discoveries.
Many drug companies argue that the risk in neuroscience simply doesn’t justify the investment. The overarching sentiment is that the brain is still a black box: good targets are few and far between; clinical trials are long and unpredictable; regulatory approval is tough; and generic competition is plentiful. For many big pharma firms, the math just doesn’t add up.
“I personally don’t find that calculus to give you the total picture,” Ehlers says. Shifting resources away from neuroscience to focus on areas like oncology, where the environment looks favorable—clear clinical trial endpoints, the opportunity for fast-track approval, an easier chance for reimbursement from payors—only makes sense in the short term, Ehlers says. But that thinking “is short sighted as to where the fundamental state of biology is in neuroscience,” he says.
Why is Ehlers so encouraged about a field that so many are walking away from? He believes that neuroscience is poised to benefit from the kind of genetic links that generated so many targets—and eventually so many targeted-drugs—in oncology. “There is going to be kind of a revolution in the next five years—it’s not going to be tomorrow…but you have to think about that inflection of opportunity over the five-to-ten year time horizon.”
To take advantage of each new genetic clue, Ehlers has revamped Pfizer’s approach to neuroscience R&D. As this week’s story explains:
In the past, big pharma often gave its scientists a mandate to work in areas such as Alzheimer’s or schizophrenia, regardless of tractable drug targets. Now at Pfizer, Ehlers says, his team is “indication agnostic.” Any program that Pfizer undertakes must have a critical mass of biological knowledge—for example, human genetics, human phenotyping, and evidence of dysfunctional neurocircuits—to convince Ehlers it’s worth pursuing. “We start there,” he says. “That hasn’t always been the case.”
Moreover, Pfizer no longer relies on mouse models as predictors for responses in humans. “We’ve for the most part stopped all rodent behavior as a model for disease and are much more about what’s happening in the brain,” he says. Scientists measure human responses to prove experimentally that a drug works.
Pfizer’s goal, according to Ehlers, is to tackle fewer projects but have more confidence in their potential for success. The result should be a drug pipeline “rooted in something more than optimism.”
He cites Huntington’s disease as one area that, even before coming to Pfizer, he saw as a prime scientific opportunity. “You know the gene, you know a fair bit about what’s going on, you have a wealth of data, tons of models, a clear clinical course, and an identifiable patient population,” he says. “If we can’t deal with that, we’re in trouble.”
Over the weekend Bristol-Myers Squibb and Pfizer announced that their blood-clot-preventing drug candidate, Eliquis (apixaban), bested the workhorse anticoagulant Coumadin (warfarin) in a large clinical trial. The results were announced at the European Society of Cardiology congress and simultaneously published in the New England Journal of Medicine. This is the first time that one of the cadre of anticoagulants seeking to replace warfarin has been shown to be superior to warfarin at preventing dangerous blood clots that can lead to strokes while also having a lower rate of bleeding compared to warfarin.
In the 18,201 patient Phase III clinical trial, called ARISTOTLE, apixaban reduced the risk of stroke in patients with an abnormal heart rhythm called atrial fibrillation by 21 percent, major bleeding by 31 percent, and mortality by 11 percent.
More statistics are available in the announcement, the journal article, and in this Forbes report, which plucks out these illustrative numbers:
The investigators calculated that for every 1000 patients treated with apixaban instead of warfarin for 1.8 years
•stroke would be avoided in 6 patients,
•major bleeding would be avoided in 15 patients, and
•death would be avoided in 8 patients.
Analysts reacted positively to the data, with Leerink Swann analyst Seamus Fernandez raising his 2017 sales estimate for apixaban by $1.1 billion to $4.1 billion in a note to investors.
We’ve previously explained how apixaban works– briefly, it blocks Factor Xa, a protease enzyme near the end of the complex biochemical pathway that regulates blood clotting. Another Factor Xa inhibitor, rivaroxaban, has been approved in Europe but awaits FDA approval. Pradaxa (dabigatran), which blocks the enzyme thrombin, has been approved by FDA for reducing the risk of stroke associated with atrial fibrillation.
So what’s the secret of apixaban’s success? Continue reading →
As reported by Nature News and Forbes’ The Medicine Show on July 20, dapagliflozin, a BMS-developed diabetes drug marketed with partner AstraZeneca, was given a “thumbs-down” by an FDA review panel on July 19. After the 9-6 final vote, panel members commented favorably on the drug’s new mechanism, but evidently felt that the safety profile could not be overlooked: the FDA committee meeting statement mentions increased risk of breast and bladder cancer, increased genital infections, and perhaps most seriously, potential for drug-induced liver injury (DILI).
Dapagliflozin has been one of the rising stars of the new class of Sodium-Glucose cotransporter 2 (SGLT2) inhibitors for diabetes treatment, whose development roster includes Johnson & Johnson, Astellas, Boehringer Ingelheim, Roche, GSK, and Lexicon (Note: see Nat. Rev. Drug Disc. 2010, 551 for a full recap). The excitement behind these drugs comes from a relatively new idea for diabetes treatment: inhibition of the SGLT2 enzyme stops the kidney from reabsorbing sugar, leading to excretion of the excess glucose in the urine, which in turn lowers blood sugar. Dapagliflozin, like most SGLT2 inhibitors, is a glucose molecule with a large aromatic group attached to the carbon atom in the spot chemists call the anomeric position. Such so-called C-glycosides are thought to have improved staying power in the bloodstream relative to O-glycosides (where the linkage point is at an oxygen atom, a more common scenario in sugars), since they are less susceptible to enzymatic breakdown.
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 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?
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/FoldRx, GSK/Amicus, GSK/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:
When the Alexandria Center for Life Sciences opened along the East River in New York last month, I admit I was skeptical about its prospects given the economic challenges for a small biotech to conduct research in NY. ImClone had signed on as the anchor tenant, but it had for years worked out of older labs in Tribeca—it’s not like they were new to the city. At the opening, one of the Alexandria representatives told me a small company would be moving in shortly, but it sounded like a services firm rather than a biotech or big pharma type.
But Alexandria offered up a release today with detail on the first five tenants in the building. ImClone’s first neighbor will be none other than Sam Waksal. That’s right, the former ImClone CEO is planting his first post-jail venture, Kadmon Pharmaceuticals, at Alexandria. It looks like the lunchtime chatter at Tom Coliccio’s ‘witchcraft, on the first floor of the biotech center, just got more interesting.
Another intriguing mention in today’s release? News that “a top-tier big pharma scientific collaboration unit for therapeutic innovation,” will soon be a resident. Last month, Pfizer said that University of California, San Francisco, would be the first partner in a network of academic collaborators spanning the globe. Anthony Coyle, head of Pfizer’s Center for Therapeutic Innovation, told me that by the end of the year, the company would be announcing two other partnerships—one in New York, the other in Boston. Notably, Pfizer is opening labs adjacent to UCSF’s campus as part of that pact. Connecting the dots, one has to wonder if Pfizer will soon have some scientists working in Manhattan. Readers? Any guesses about what other big pharma might be eyeing New York as its next research hub. Feel free to leave them in the comments.
What you’re looking at is an overview of the complex biochemical pathway behind blood clotting, and a smattering of the drugs researchers are developing to control clotting for preventing strokes and more.
Over at Terra Sigillata, David Kroll has two back-to-back posts about some of these drugs that are worth reading.
In the first post, Kroll discusses news out of the American Heart Association’s annual meeting: Rivaroxaban (Xarelto), a blood clot preventing drug from Bayer and J&J, has been shown to be about as efficacious as the established medication warfarin (coumadin) and better with regard to spontanous bleeding complications. He also dishes on some of the fascinating historical context behind the drugs.
In the second, he brings attention to Pfizer and BMS’s announcement that they are halting a trial of apixaban, their investigational blood clot preventing medication. Eight other apixaban trials are ongoing. We covered some apixaban news last June, when a different apixaban clinical trial was stopped early because an independent analysis concluded that the drug candidate was more effective than aspirin at reducing strokes and blood clots in patients with a common abnormal heart rhythm.
As we’ve written in C&EN, many factors will determine whether patients at risk of strokes or other dangerous blood clots will end up taking warfarin or will take one of the new drugs. Boehringer-Ingelheim’s Pradaxa (dabigatran), which acts at a different target from apixaban and rivaroxaban, is already approved by FDA. Rivaroxaban and Pradaxa are already approved in a number of other countries for short-term use. Each drug is slightly different, from how many times a day it must be taken, to how much of it is cleared via the kidneys (a potential issue for patients on dialysis or other kidney conditions), and much more. And of course, a big question is what the difference in cost is going to be- warfarin pills are cheap but the quality of life costs- incessant testing and diet monitoring- can be steep.
Pfizer has committed up to $85 million over five years to an expansive research agreement with the University of California, San Francisco, intended to speed the development of new biologic-based medications. More critically, the relationship with UCSF will be the first spoke in a network of academic collaborators, with Pfizer at the hub. Called the Center for Therapeutic Innovation, the goal is to bridge the gap between basic science and early clinical studies of potential drug candidates.
Anthony Coyle, former head of respiratory, inflammation, and autoimmune disease research at MedImmune, will lead the network. Coyle says CTI will eventually be comprised of seven or eight partners: three or four in the U.S., one or two in Europe, and the remainder in Asia or Australia. Expect to see two more U.S.-based partners, one in NY and the other in Boston, added to the network by the end of the year, he adds.
The creation of the CTI is Pfizer’s latest shake-up of the model for industry-academic collaborations. If you’ll recall, last spring, Pfizer caused a stir when it said it would give scientists from Washington University‘s School of Medicine access to data on 500 compounds that have gone through or are in some stage of clinical development. The hope is that fresh eyes with deep insights into the biology of disease and drug targets might lead to new uses for the compounds. See our recent cover story on the deal for much more detail on how that arrangement works.
Ultimately, Pfizer hopes that by breaking down some of the barriers that have hindered an open exchange between industry and academia—the right to publish, ownership of intellectual property, shared profits on products, to name a few—it will be able to get new drugs to market faster.
Coyle says the CTI will be solely focused on biologic-based drugs, mainly because he wants each center to be fairly autonomous and able to make decisions quickly. With the infrastructure required to develop small molecules, they would have had to rely on medicinal chemists “in distant locations,” and would run the risk of creating an “overburdened” project.
The first step in the UCSF collaboration will be a trip by Coyle and other Pfizer executives to the campus in December to explain the program. Because Pfizer believes the projects will only work if scientists are working side-by-side, the company will set up new labs that can accommodate up to 40 scientists close to the UCSF campus.
University scientists will have access not just to Pfizer’s drug development knowledge, but to its research tools—of particular note is that Pfizer is making its phage display libraries accessible to those working on joint projects. Pfizer, meanwhile, will have easier access to tissue samples and tools that can help it quickly understand which patient populations its drug candidates will be relevant in.
Proposals by UCSF scientists are reviewed by a steering committee comprised of four members from the university, and four members from Pfizer. And just like a biotech is funded, follow-up cash will be linked to the project achieving milestones.
“It’s almost like VC-based funding,” Coyle says. The deals are light on capital upfront, “and then projects are funded as they are successful. If there’s no success or a project didn’t meet the appropriate milestone, then there’s no additional funding.”
The Economic Times is reporting that Pfizer is interested in buying the U.S. and European rights to Bangalore-based Biocon’s insulin franchise in a deal that would include a $200 million upfront payment. Rumors that Pfizer would buy Biocon’s oral insulin product emerged in August, but the specifics on a possible pricetag have caused shares of the Indian company to rise over 8%.
Biocon’s diabetes pill is in Phase III trials in India and Phase I studies in the U.S. The potential for an oral insulin product is vast, but so is the risk—getting the right balance in insulin administration is a tricky business. (Click here for my colleague Ann Thayer’s take on efforts to make inhaled or oral insulin products.) One has to wonder how much money Pfizer would be willing to pay for another alternative insulin after the colossal failure of the inhaled insulin Exubera. Low demand for the treatment prompted Pfizer to pull it from the market a year after its approval, costing the company some $5 billion after licensing fees, R&D costs, and write-offs.
To be fair, an insulin pill has been the holy grail for diabetes researchers for some time. It would be less onerous than daily injections and more discrete than the unwieldy to downright ridiculous inhaled insulin instruments.
Some background on Biocon’s technology: Biocon’s oral insulin program came from its 2006 acquisition of Nobex, a N.C.-based biotech that developed a way to make a pill form of biologics, which normally need to be given as an injection or IV infusion. Nobex used what it called “PegAlkylation” technology, which links a polyethylene glycol chain (those same PEGs used to improve the delivery of interferons and other large molecules) and an alkyl to a biologic like a protein or peptide. The design creates a molecule with a water-soluble and fat-soluble end that can travel through the myriad environments inside our bodies. Nobex claimed its oral insulin drug effectively reproduces the “first-phase spike,” or the large hit of insulin the pancreas puts out after a meal, a challenge for injectable and inhaled forms of insulin.
Pfizer wouldn’t be the first big pharma to invest in an insulin pill. GlaxoSmithKline licensed an earlier version of Nobex’s oral insulin drug, but gave back the rights in late 2003. Nobex abandoned worked on that molecule in favor of a newer and better one, which Biocon licensed in 2004, prior to its acquisition of Nobex.
Oral insulin aside, its worth noting that today’s ET story says the $200 million is for Biocon’s insulin portfolio, whereas earlier stories focused on Pfizer’s interest in the oral insulin program. European regulatory authorities recently gave the nod to allow Biocon to start Phase III trials of a biosimilar insulin, a product produced in yeast that Biocon already sells in India. Like several of its big pharma compatriots, Pfizer is making a big push into biosimilars, and was on the lookout for acquisitions that would beef up its portfolio of copycat biologics. One has to wonder whether the rumored deal would be for the whole enchilada, or just oral insulin. If the former is true, the $200 million starts to sound like a steal.