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Bayer to Eliminate Unsightly Chin Fat
As my husband and I recently looked through photos of our wedding, he kept repeating the same thing: “Yikes, check out my triple chin.” Click. “Another triple chin.” Click. “Hmm, maybe I need to work out.”
In reality, his perceived folds of flab were a result of unfortunate camera angles (I swear, dear. Your chin is splendid.). But if a day comes when he genuinely suffers from chin bulge, Bayer might have just the solution. Yesterday, the company agreed to fork over $43 million upfront and upwards of $300 million in milestone payments for Kythera Biopharmaceuticals’ ATX-101, an adipolytic agent “designed to reduce small volumes of facial fat.” Yes, that’s right, folks: it’s a chin fat drug.
Because I tend to cover pharmaceuticals that are more in the disease-modifying category rather than those in the aesthetics-modifying category, I was pretty shocked by the price tag. Then I took a look at Allergan’s sales forecast for its wrinkle smoother Botox—the company is predicting it will bring in about $1.3 billion this year. (Well, that’s before subtracting out the $600 million Allergan agreed to pay today to settle criminal and civil charges related to the marketing of Botox.)
In other words, the potential market for ATX-101 seems pretty vast. Indeed, I imagine my husband isn’t the only one to look at a photo (poorly angled or not) and cringe. ATX-101 is in Phase II studies, and seems to be administrated in a relatively painless injection.
All this made me wonder how one goes about getting rid of small fat deposits without, well, sucking them out. It looks like the folks at Kythera, which is conveniently based in Los Angeles, first thought the active component in the formulation of ATX-101 was phosphatidylcholine, a major component of biological membranes that sports a polar head and fatty acid tails. However, further studies showed that deoxycholate, a secondary bile acid put into the formulation to make the phosphatidylcholine micelles soluble, was actually the secret to getting rid of unsightly chin fat. Deoxycholate, a detergent, causes a shift in the osmotic balance of a cell–in other words, water rushes into the fat cell, causing it to burst. The finding was curious, as deoxycholate appeared to be only affecting fat tissues when administered in vivo. Kythera eventually determined that deoxycholate isn’t necessarily selective for fat cells, but that tissues in the subcutaneous fat that are protein rich are resistant to its effects. Hence, when administered locally, it appears to be able to get rid of the fat without impacting other tissues. And there you have it, drug goes in, fatty chin goes out. Since later stage trials are pending, the chin-fat sensitive will have to stick to photoshop for now.
Pharma Blogging Panel at ACS Boston
Welcome to the live coverage of the Chemical & Pharma Blogging panel. Yes, this pharma blog is live blogging the pharma blogging session. It’s very meta. On our panel today is Derek Lowe of In the Pipeline, Ed Silverman of Pharmalot, David Kroll of Terra Sigillata, and Mike Tarselli of Scripps Florida, and our moderater is none other than the Haystack’s Carmen Drahl.12:08 A slight delay as the crowds descend upon the boxed lunches.
12:16 Derek Lowe is up first.
12:20: Derek started blogging in January or February of 2002. Though he worried at the time he wouldn’t have enough to write about– appears the supply of material is inexhaustable. It helps that he talks about business, IP, legal, science and he tries to rotate between those. It keeps the readership reasonably happy or at least equally unhappy. “I know if i I talk about IP for more than two posts, I can see the readership dropping.” It’s like spray repellant.
12:22 Derek gets about 15-20k pageviews per day. Big spike at lunchtime. Likes to think he has had a profound negative effect on productivity for the country. Readership seems to be a lot of chemists and people who work in the drug industry, but also a lot of folks outside the field.
12:24 Nabakov extensively quoted. Derek is literary, not just scientific!
12:25: A way to tell people where drugs really come from. Why do your prescriptions cost so much? Derek: “It’s me.”
12:26 Ed Silverman from Pharmalot is up next.
12:28 Ed comes at blogging from a different perspective: “I’m a journalist of all thing.” Started out on the pharma beat at the NJ Star-Ledger in 1995, and after ten years he proposed a blog. Got the greenlight in 2006–came up with the name “pharmalot,” with idea of covering what didn’t get covered in mainstream media. Started in Jan ’07.
12:30 Blogging has been an interesting experience–writing a blog has been one of the best career decisions he made. Keeps him in front of issues, meeting people, etc. Trying to cover a smattering of different things, and comes to pharma industry from a different perspective– as an outsider.
12:31 Ed also sees the crowd go quiet when he writes about patent stuff. Ah, the challenges of making IP enticing…
12:33 Now up, David Kroll of Terra Sigillata
12:35 A pharmacologist by training, but he does play well with chemists. He likes to think blogging serves bost chemistry and pharmacology. He grew up within sight of the Roche tower and always wanted to work for a pharma company. Life changed, and landed in academia.
12:37 Terra Sigillata is latin for “sealed earth”–It was the first trademarked medicine that came from a special clay. Abel Pharmboy (his pseudonym on the blog) comes from John Jacob Abel, the father of American pharmacology.
12:39 He came about blogging differently–growing up in NJ, always interested in mass communication and in teaching and conveying scientific knowledge to other folks. The greatest benefit of this medium is the ability to communicate science to non-scientists.
12:42 When he told people he was working on cancer, everyone was always interested and had questions. When regular folks felt like they had access to complex technical info, they seized upon it and got excited about it. “We tend to dumb down our communications too much.”
12:42 Derek Lowe was an inspiration for David’s blog. And felt like he really could perform a public service by talking about the risks and (few) benefits of herbal medicines. In 2006, was invited to join ScienceBlogs.com, which he says helped him develop breadth as a scientists by interacting with anthropologists, scientific ethicists, etc.
12:43 David left ScienceBlogs after PepsiGate of July 2010.
12:45 David’s joining C&ENtral Science! He will be moving to C&EN’s website–look for the first post up today! And he will be blogging under his real name.
12:48 David is talking about the many ways that blogging has benefited his career, his students, and more generally has enabled him to interact with a larger community.
12:49 Blogging has given him a chance to interact with a lot of communicators who have then come to the university to speak to students.
12:51 And blogging was written into one of his grants as a means of trying to make students more competitive for graduate school. Putting in a blogging mechanisms is helping students develop writing skills, particularly about science.
12:52 David’s top posts? Components of marijuana, horny goat weed, “stiff nights” (will leave it to the reader’s imagination to figure out what that herbal supplement is for). Even though his blog is dead on ScienceBlogs, it still gets about 900 hits a day from google searches.
12:54 Mike Tarsellis at Scripps Florida is up now. He’s talking about how he uses pharma/chem blogs.
12:55 Mike’s giving us his daily blog-reading schedule. In the Pipeline and Pharmalot are the morning coffee reads. Mid-morning? ACS Careers & Chemjobber (he’s a postdoc). Mid-afternoon? The Haystack (Aw…)
12:57 Mike did a survey of some fellow chemists, and most of them read them, but few trust the info. The idea was too many opinions, too few citations or too little verification.
12:58 Totally Synthetic most read among the scientists he works with–followed by the long-defunct (but much missed) Tenderbutton. When he asked them what they wanted out of a blog, they asked for more practical, hands-on info, more citations, yet also more gossip, and trouble-shooting advice. Most wanted: peer review discussion.
1:02 Some examples of crowd-sourced peer review that have or are having an impact on science. He’s talking about a controversial paper on biaryl formation by DMEDA organocatalysis–first post on this was by Derek on August 5. Has lead to a cadre of chemists all over the world repeating these reactions.
1:05 Q&A is now starting! Send your questions to me via twitter @lisamjarvis or in the comments to this post!
1:08 First question is basically whether you had a comfort with writing before starting a blog. Derek says he saw it as a strength of his that he thought he should try to put to use; David used to write for student newspapers before becoming a scientist; Ed was an accounting major in college, but loved literature; and Mike says he just likes to speak a lot.
1:14 A grad student asks about the potential pitfalls and how to navigate writing a blog as a grad student (her university wants her to write a blog). Derek talks about using his real name: he decided in the end it would come across as more trustworthy and it could only help to write under his real name. But blogging in grad school is a tough one because of relationship with professors, he notes. David thinks the university is forward thinking to want her to blog, and that it’s a great idea. The trick is to keep your experiences veiled enough, but it could be a tremendous opportunity to get away from the isolation many feel during PhD training. Ed talks about making the switch from working at a daily mainstream newspaper to blogging, which has some negative connotations. He’s dealt with that by being very transparent and by responding to comments without inserting himself into the conversation. Mike talks about tenderbutton, whose professor specifically asked him to stop blogging. Many advisors want you to be focused on work, and there can be a backlash as its seen as disrupting that.
1:16 What are the advantages of blog moderation? Derek takes down personal insults unless they’re interspersed with something interesting…David has only censored 2 comments in 5 years.
1:17 A question from chemjobber: How many non-reporter (i.e. non-professional journalist) blogs can the chem/pharma blogosphere support?
1:20 Ed tries to maintain civil order, and only inserts himself if there’s a question that needs answering.
1:22 Someone who recently finished his PhD thanks Derek for providing a forum for having insight info on what is going on inthe industry. He ended up at Genentech. Derek says he hopes that blogs can give grad students and post docs a look into what its really like because he had no idea what was going on in industry before he joined.
1:30 Finally going to get to chemjobber’s question!
1:34 Ed: Fewer than 1? The good blogs I look at are people who are already working regular jobs– they’re lawyers, they’re scientists, they’re professors, they’re not yet media moguls. Derek would agree: he hasn’t tried to turn his blog into a profession cause he’s always had drug discovery as his day job. Thinks he may e eating weeds out of his backyard if he tried to do that. David notes that you get $25/month per 10k pageviews on ScienceBlogs, which isn’t really going to support anyone. PZMeyers is probably the only one who can support himself that way.
1:37 A professor in the audience asks: when you sit down with a paper you want to write about, and you are aiming at a scientist (positively or negatively) rather than at a company, do you approach it differently? David notes that he just finished a five-year stint at NIH, so avoids anything related to that. And he tends to stick to positive papers. Derek will often write about a paper because he’s excited about it and thinks its neat stuff. But if he’s saying something nasty–which he does–he tries to put a disclaimer in there.
1:40 Mike: Academia is very compartamentalized, and one of the things blogs do for science is popularizes some things. If Derek puts up a paper, we are all deconstructing it by lunchtime, good or bad.
1:46 Someone asks who should get more attention? David suggests White Coat Underground while Ed thinks FDA Law Blog is good.
1:50 Carmen is wrapping things up and letting our illustrious panel off of the hot seat after two hours!
Aileron & Roche in Stapled Peptides Pact
Roche has agreed to pay up to $1.1 billion for access to technology at Aileron Therapeutics, a tiny Cambridge, Mass.-based biotech focused on developing stapled peptides. As part of the deal, Roche and Aileron will develop drug candidates against five targets.
Stapled peptides make intriguing drug candidates for their ability to access previously intractable targets. As we’ve described:
Protein-embedded α-helices mediate key protein handshakes in cancer, HIV, and other diseases. But actually using an α-helix as a drug has proven tricky. So-called stapled α-helices, boasting sturdy cross-links between nonnatural amino acid side chains, just might change that. This class of stabilized peptides can regulate signaling pathways to subvert cancer. They also appear to overcome several of the usual problems that have hampered the development of peptide drugs.
Stapled peptides are locked into the biologically active shape, enabling the drug to penetrate the cell and bind tightly to protein surfaces. Last fall, Harvard chemical biologist and Aileron’s scientific founder Gregory L. Verdine and colleagues showed the helix-stabilizing strategy could be used to turn off the Notch transcription factor complex, a master cell regulator in cancer that has gone awry in over half of patients with a certain type of leukemia. It was the first direct inhibitor of the Notch complex.
Aileron gets $25 million upfront and R&D funding, but could score a bounty in milestones if drug candidates against all five targets reach the market. Roche was clearly keeping close tabs on the technology. The Swiss pharma firm’s corporate venture fund was one of several big pharma funds to invest in the $40 million round raised by Aileron last summer.
RNAi Roundup #4
While everyone was focused on Avandia & Qnexa, a spate of RNAi-related news slipped past us:
–Tekmira Pharmaceuticals scored a major contract through the U.S. Department of Defense’s Transformational Medical Technologies program. The biotech will use its lipid nanoparticle technology to deliver siRNA tailored to treat the Ebola virua. Tekmira could snag up to $34.7 million over the next three years to help bring the Ebola virus candidate through an investigational new drug filing and a Phase I clinical trial. If the government decides to extend the contract beyond Phase I, Tekmira is eligible for up to $140 million in funding. The contract comes a few months after Tekmira and the U.S. Army Medical Research Institute of Infectious Diseases published an article in The Lancet showing its lipid nanoparticle could protect non-human primates against the Ebola virus.
–Nitto Denko of Japan and Fremont, Calif.-based Quark Pharmaceuticals will jointly develop RNAi-based drugs to treat fibrotic diseases. The companies will use Quark’s RNAi technology and patent fortress, and Nitto Denko’s drug delivery technology. Terms weren’t disclosed, but the companies say they “have an initial budget of double-digit million US dollars” with the goal of filing their first investigational new drug application with FDA by early 2012. Nitto, which has expertise in polymeric formulations, says it picked Quark because of the chemical modification it had made to the siRNA that have eliminated worries over an immune response from the therapeutic.
–AstraZeneca has extended its siRNA research pact with Silence Therapeutics by one year. The companies have worked together since 2007 on finding five novel siRNA therapeutic molecules for oncology and respiratory diseases. The duo forged a separate pact around siRNA delivery in April.
–The NIH has awarded RXi Pharmaceuticals a small business innovation research grant (SBIR) worth $600,000 to support the pre-clinical development of RNAi-based therapeutics. NIH has seen a surge in applications for SBIR grants amid a tougher financing climate for biotechs. RXi is eligible for an additional $1 million per year for up to three years during the second phase of the SBIR’s program.
–Alnylam Pharmaceuticals has dosed its first patient in a Phase I clinical trial of ALN-TTR01, a systemically-delivered RNAi therapeutic for the treatment of transthyretin (TTR)-mediated amyloidosis, a rare, inherited disease in which a mutation in the TTR gene causes the build up of the toxic protein in the several tissues in the body. This study is designed to test the safety of the drug and show whether the drug is impacting TTR levels in the blood.
Future Cloudy for GSK’s Avandia
A panel of FDA advisors decided yesterday that GlaxoSmithKline’s diabetes drug Avandia should either be withdrawn from the market or its use seriously restricted. The panel had been assembled after several years of ongoing questions over the safety of the drug, which has been linked to an increased risk of cardiovascular events.
The final vote came down to this: 12 panel members said the drug should be removed from the market, while 10 said it could stay on the market, but with strong restrictions on who could both prescribe and take the drug. The remaining members voted to either keep the label the same or revise it somehow to better reflect the safety concerns.
With that mixed bag in hand, its up to FDA to decide what to do.
For those of you having trouble keeping track of the ins an outs of the Avandia story, here’s a little primer. GlaxoSmithKline’s Avandia problems—the public ones, at least—began in May 2007, when the safety of the drug was questioned by Cleveland Clinic cardiologist Steve Nissen, previously known for blowing the lid off the cardiovascular issues associated with Merck’s arthritis drug Vioxx. In an article in The New England Journal of Medicine, Nissen said an analysis of the combined data from 42 previous clinical trials of Avandia showed that patients taking the drug were 43% more likely to have a heart attack than those who weren’t. FDA issued a safety alert about the drug, which brought in $3 billion for GSK in 2006.
In August 2007, an FDA advisory panel voted 22-1 to keep Avandia on the market. Still, Avandia franchise sales fell 22% to $2.4 billion in 2007.
But GSK’s troubles with Avandia go beyond the financial pain of lost sales. As you might expect, the company is at the receiving end of a flood of lawsuits related to the drug. It could get worse. This week, the NY Times said it had reviewed internal documents suggesting GSK knew as early as 1999 that the drug posed a safety risk, but actively worked to conceal those findings from FDA. Yesterday, GSK said it would take a charge of $2.36 billion in the second quarter, in part to help pay to settle lawsuits related to Avandia and its antidepressant Paxil.
Avandia works by lowering blood glucose levels by increasing cells’ responsiveness to insulin. This isn’t the first time drugs acting on Avandia’s target, the peroxisome proliferator-activated receptor (PPAR), have run into safety trouble. In 2005, Merck and Bristol-Myers Squibb withdrew a New Drug Application for their PPAR agonist Pargluva after FDA asked for a five-year cardiovascular safety study. And Warner-Lambert pulled the drug Rezulin from the market in 2000 after it was shown to cause liver toxicity.
Merck Adds to Industry-wide R&D Cuts
Merck is finally revealing details of the deep cuts it planned to make in its organization following its acquisition of Schering-Plough. We thought this would be a good time to remind readers of the extensive R&D cuts the pharmaceutical industry has made in the last two years. One has to wonder what will be left to trim during the next round of cost-savings efforts. For a more complete chart that shows how this process started back in 2008, see here.
2009:
January: Pfizer buys Wyeth, plans to eliminate 15% of the combined workforce of about 128,000.
March: Merck acquires Schering-Plough, plans to cut 15% of combined workforce of 106,000.
April: Sanofi-Aventis overhauls its pipeline. Research on 14 drug and vaccine candidates, including seven in Phase II or III trials, is discontinued.
September: Lilly reorganizes into five units—oncology, diabetes, established markets, emerging markets, and animal health—and plans to eliminate 5,500 jobs, or nearly 14% of employees, by the end of 2011.
November: Pfizer plans to shutter six of its 20 research sites to reduce overall lab space by 35%. Research will end in South Brunswick, N.J.; Chazy and Rouses Point, N.Y.; Sanford, N.C.; and Gosport and Slough, England. Roughly 1,300 researchers work at the locations earmarked for closure.
2010
January: GSK proposes ending R&D at several sites, including Tonbridge, England; Verona, Italy; Zagreb, Croatia; and Poznań, Poland. Preclinical development ends in Mississauga, Ontario, and neurosciences drug activity closes in Harlow, England.
February: AstraZeneca plans to cut 8,000 jobs on top of the 15,000 positions targeted for elimination between 2007 and 2009. The company drops 20 compounds from development and ends discovery research in 10 diseases and most vaccines. It will close sites in Leicestershire and Cambridge, England, and Lund, Sweden, and end discovery research in Wilmington, Del.
May: Takeda plans to cut 1,600 jobs from its North American operations, including 20% of staff at its Lake Forest, Ill., R&D center.
July: GSK sells its Verona, Italy, site to Aptuit, transferring 500 staff—almost all graduate-level scientists—to the contract research organization.
July: Merck says it will cut exit operations at eight R&D sites and eight manufacturing sites as part of its previously announced plans to shed 15% of its combined workforce following the acquisition of Schering-Plough. R&D facilities to be phased out over the next two years are: Montreal, Canada; Boxmeer (Nobilon facility only), Oss, and Schaijk, Netherlands; Odense, Denmark; Waltrop, Germany; Newhouse, Scotland; and Cambridge (Kendall Square), Massachusetts, U.S. Manufacturing facilities affected include sites in Comazzo, Italy; Cacem, Portugal; Azcapotzalco, Mexico; Coyoacan, Mexico, and Santo Amaro, Brazil. The Mirador, Argentina, and Miami Lakes, Florida, facilities will be sold. Chemical manufacturing will be phased out at the legacy Merck site in Singapore, but the legacy Schering-Plough site there will continue operations.
Merck’s Kamarck Talks Biosimilars
Reuters has a report out today on the potential market for biosimilars, or generic versions of biologic drugs. The players will be few, and the challenges many, the report suggested.
“Access to the nascent market for so-called biosimilars, worth an estimated $10 billion (6.6 billion pounds) by 2015, will be limited to a close circle of specialist companies with the means to invest heavily and to fend off a legal onslaught, analysts said.”
Coincidentally, I sat down earlier this week with Michael Kamarck, the new head of the company’s biosimilars arm Merck Bioventures. Kamarck, who previously headed up biologics manufacturing at Wyeth, had a strikingly similar perspective on the market. He also expects few players based on a high barrier to entry. Biosimilars players will need to have technology capabilities (see Genzyme’s woes for the challenges of manufacturing biologic products), the financial mettle to conduct large clinical trials, the ability to navigate a still fuzzy regulatory pathway, and the right commercial strategy once a biosimilar is approved.
When asked about drug pricing, Kamarck noted that in markets with a limited number of players, prices tend to stabilize after an initial drop. The biosimilars approved in Europe generally cost about 70% of the innovator’s price, and he expects the U.S. market will shake out in a similar way. “We think that’s a good model and provides a fair return and a large advantage for patients,” he said.
Why so little of a discount? As the Reuters article explains, the “development, production and marketing of a copycat version of biological drugs already cost about 50 times the amount needed to launch a generic copy of conventional chemical drugs.”
However, biosimilars players could have an advantage of more cost-effective manufacturing. When asked whether he was worried about innovators simply lowering their price or selling their own biosimilars, a strategy Amgen seems prepared to pursue, Kamarck pointed to the significant improvements in yields of the mammalian cell culture lines used to make many top-selling biologics. The innovator, on the other hand, has to go through FDA to make changes to their manufacturing process. “It might well be that coming into the game now, you can make manufacturing improvements to the processes that the innovator is stuck with,” he adds.
Merck has two biosimilars, both acquired last year from Insmed, in the clinic: MK-4214 and MK-6302, generic versions of Amgen’s Neupogen and Neulasta, respectively. The company plans to have five biosimilars in late development n 2012, though isn’t identifying which innovator medicines they will be copying. Development of MK-2578, a similar version of Amgen’s Aranesp, was abandoned earlier this year due to regulatory and market challenges for erythropoietin-stimulating agents. The drug had been considered a “biobetter” rather than a biosimilar, because it was being made using yeast-based technology rather than the same kind of cell line as Amgen’s drug.
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