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Posts Tagged ‘Sanofi’


 

Lemtrada (alemtuzumab) for the treatment of relapsing forms of multiple sclerosis – Biologics License Application: FDA – Not ready for approval!

Reporter: Aviva Lev-Ari, PhD, RN

 

Genzyme Receives Complete Response Letter from FDA on LemtradaTM (alemtuzumab) Application 

Paris, France – December 30, 2013 – Sanofi (EURONEXT: SAN and NYSE: SNY) and its subsidiary Genzyme announced today that it has received a Complete Response Letter from the U.S. Food and Drug Administration (FDA) for its supplemental Biologics License Application seeking approval of Lemtrada (alemtuzumab) for the treatment of relapsing forms of multiple sclerosis.

A Complete Response Letter informs companies that an application is not ready for approval. FDA has taken the position that Genzyme has not submitted evidence from adequate and well-controlled studies that demonstrate the benefits of Lemtrada outweigh its serious adverse effects. Genzyme understands that the conclusion is related to the design of the completed Phase 3 active comparator studies of Lemtrada in relapsing-remitting MS patients. FDA has also taken the position that one or more additional active comparator clinical trials of different design and execution are needed prior to the approval of Lemtrada.

Genzyme strongly disagrees with the FDA’s conclusions and plans to appeal the agency’s decision.

“We are extremely disappointed with the outcome of the review and the implications for patients in the U.S. suffering with multiple sclerosis who remain in need of alternative therapies to manage a devastating disease,” said Genzyme President and CEO, David Meeker, M.D. “We strongly believe that the clinical development program, which was designed to demonstrate how Lemtrada compares against an active comparator as opposed to placebo, provides robust evidence of efficacy and a favorable benefit-risk profile. This evidence was also the basis for the approvals of Lemtrada by other regulatory agencies around the world.”

Lemtrada is approved in the European Union, Canada, and Australia, and additional marketing applications for Lemtrada are under review by regulatory agencies around the world.

Sanofi does not anticipate that the CVR milestone of U.S. approval of Lemtrada by March 31, 2014 will be met.

About Lemtrada™ (alemtuzumab) 

The Lemtrada clinical development program included two pivotal randomized Phase III studies comparing treatment with Lemtrada to Rebif® (high-dose subcutaneous interferon beta-1a) in patients with RRMS who had active disease and were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II), as well as an ongoing extension study. In CARE-MS I, Lemtrada was significantly more effective than Rebif at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a.

The most common side effects of Lemtrada are infusion associated reactions, infections (upper respiratory tract and urinary tract), lymphopenia and leukopenia. Serious autoimmune conditions can occur in patients receiving Lemtrada. A comprehensive risk management program will support early detection and management of these autoimmune events. 2/3

 

Alemtuzumab is a monoclonal antibody that selectively targets CD52, a protein abundant on T and B cells. Treatment with alemtuzumab results in the depletion of circulating T and B cells thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab has minimal impact on other immune cells. The acute anti-inflammatory effect of alemtuzumab is immediately followed by the onset of a distinctive pattern of T and B cell repopulation that continues over time, rebalancing the immune system in a way that potentially reduces MS disease activity.

Genzyme holds the worldwide rights to alemtuzumab and has primary responsibility for its development and commercialization in multiple sclerosis. Bayer HealthCare holds the right to co-promote alemtuzumab in MS in the United States. Upon commercialization, Bayer will receive contingent payments based on global sales revenue.

About Genzyme, a Sanofi Company 

Genzyme has pioneered the development and delivery of transformative therapies for patients affected by rare and debilitating diseases for over 30 years. We accomplish our goals through world-class research and with the compassion and commitment of our employees. With a focus on rare diseases and multiple sclerosis, we are dedicated to making a positive impact on the lives of the patients and families we serve. That goal guides and inspires us every day. Genzyme’s portfolio of transformative therapies, which are marketed in countries around the world, represents groundbreaking and life-saving advances in medicine. As a Sanofi company, Genzyme benefits from the reach and resources of one of the world’s largest pharmaceutical companies, with a shared commitment to improving the lives of patients. Learn more at http://www.genzyme.com.

About Sanofi 

Sanofi, an integrated global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and the new Genzyme. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

Genzyme® is a registered trademark and LemtradaTM is a trademark of Genzyme Corporation. Rebif® is a registered trademark of EMD Serono, Inc.

Sanofi Forward Looking Statements 

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, the Group’s ability to benefit from external growth opportunities, trends in exchange rates and prevailing interest rates, the impact of cost containment policies and subsequent changes thereto, the average number of shares outstanding as well as those discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2012. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. 

SOURCE

http://en.sanofi.com/Images/35285_20131230_Lemtrada_en.pdf

 

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Two Mutations, in the PCSK9 Gene: Eliminates a Protein involved in Controlling LDL Cholesterol

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 11/15/2013

Relax, PCSK9ers: FDA won’t roadblock blockbusters from Sanofi, Amgen

By Damian Garde

On the heels of new guidelines casting doubts on a much-hyped new class of cholesterol drugs, the FDA said it would not demand long and costly outcomes trials before approving PCSK9 treatments from the likes of Amgen ($AMGN), Sanofi ($SNY) and Regeneron ($REGN), clearing the way for treatments expected to rake in up to $3 billion a year.

As Bloomberg reports, the FDA plans to stick to its guns in vetting cardiovascular drugs, looking at reductions in LDL cholesterol and blood pressure as surrogate endpoints for long-term health benefits. That’s a relief for the developers of PCSK9-targeting drugs, who have faced mounting uncertainty about what they’ll need to do to get their would-be blockbusters to market. Partners Sanofi and Regeneron lead the pack with the promising alirocumab, followed by Amgen, Pfizer ($PFE) and numerous others.

Earlier this week, the American College of Cardiology and the American Heart Association put out new guidelines for prescribing cholesterol treatments, recommending tried-and-true statins over more novel therapies because the old drugs’ down-the-line cardiovascular benefits are well-told. That stirred up long-running concerns that the FDA would toughen up its requirements for the coming crop of PCSK9 treatments, asking drug developers to dump millions into long-term studies that demonstrate hard outcomes

But while PCSK9 developers may not have to worry about new regulatory hurdles, what’s good enough for the FDA won’t necessarily sway payers, and the billion-dollar sales estimates tied to PCSK9 drugs are contingent on widespread adoption. With that in mind, Pfizer is plotting a massive, 22,000-patient outcomes trial, looking to demonstrate the PCSK9-targeting RN-316’s ability to improve cardiovascular health in the long run, a move that may spur its competitors to follow suit.

And the FDA’s conventional wisdom on cardiovascular endpoints may not stand pat. Eric Colman, a deputy director at CDER, told Bloomberg the agency is keeping a close eye on a post-market study of Merck’s ($MRK) Vytorin, and if the drug’s LDL-lowering ability doesn’t translate to lower rates of cardiovascular events, it may well rethink its requirements.

Related Articles:

AstraZeneca wins, Merck and AbbVie lose with new statin-use guidelines

Sanofi, Regeneron take the lead in blockbuster PhIII race of PCSK9 drugs

Pfizer bets big on PCSK9 with ‘massive’ Phase III outcomes study

 SOURCE

From: FierceBiotech <editors@fiercebiotech.com>
Reply-To: <editors@fiercebiotech.com>
Date: Fri, 15 Nov 2013 17:56:42 +0000 (GMT)
To: <avivalev-ari@alum.berkeley.edu>
Subject: | 11.15.13 | Sanofi, Amgen dodge PCSK9 hurdles

 

http://www.nature.com/news/genetics-a-gene-of-rare-effect-1.12773?goback=%2Egde_96118_member_230797138

Genetics: A Gene of Rare Effect

A mutation that gives people rock-bottom cholesterol levels has led geneticists to what could be the next blockbuster heart drug.

Stephen S. Hall

09 April 2013
ADAPTED FROM: PETER DAZELEY/GETTY

Indeed, Tracy’s well-being has been inspiring to doctors, geneticists and now pharmaceutical companies precisely because she is so normal. Using every tool in the modern diagnostic arsenal — from brain scans and kidney sonograms to 24-hour blood-pressure monitors and cognitive tests — researchers at the Texas medical centre have diagnostically sliced and diced Tracy to make sure that the two highly unusual genetic mutations she has carried for her entire life have produced nothing more startling than an incredibly low level of cholesterol in her blood. At a time when the target for low-density lipoprotein (LDL) cholesterol, more commonly called ‘bad cholesterol’, in Americans’ blood is less than 100 milligrams per decilitre (a level many people fail to achieve), Tracy’s level is just 14.

A compact woman with wide-eyed energy, Tracy (not her real name) is one of a handful of African Americans whose genetics have enabled scientists to uncover one of the most promising compounds for controlling cholesterol since the first statin drug was approved by the US Food and Drug Administration in 1987. Seven years ago, researchers Helen Hobbs and Jonathan Cohen at UT-Southwestern reported1 that Tracy had inherited two mutations, one from her father and the other from her mother, in a gene called PCSK9, effectively eliminating a protein in the blood that has a fundamental role in controlling the levels of LDL cholesterol. African Americans with similar mutations have a nearly 90% reduced risk of heart disease. “She’s our girl, our main girl,” says Barbara Gilbert, a nurse who has drawn some 8,000 blood samples as part of Cohen and Hobbs’ project to find genes important to cholesterol metabolism.

Of all the intriguing DNA sequences spat out by the Human Genome Project and its ancillary studies, perhaps none is a more promising candidate to have a rapid, large-scale impact on human health than PCSK9. Elias Zerhouni, former director of the US National Institutes of Health (NIH) in Bethesda, Maryland, calls PCSK9 an “iconic example” of translational medicine in the genomics era. Preliminary clinical trials have already shown that drugs that inhibit the PCSK9 protein — used with or without statins — produce dramatic reductions in LDL cholesterol (more than 70% in some patients). Half-a-dozen pharmaceutical companies — all aiming for a share of the global market for cholesterol-reducing drugs that could reach US$25 billion in the next five years according to some estimates — are racing to the market with drugs that mimic the effect of Tracy’s paired mutations.

Free interview

Stephen Hall talks about Sharlayne’s unusual condition and whether similar cases might lead to a new line of drugs.

Zerhouni, now an in-house champion of this class of drug as an executive at drug firm Sanofi, headquartered in Paris, calls the discovery and development of PCSK9 a “beautiful story” in which researchers combined detailed physical information about patients with shrewd genetics to identify a medically important gene that has made “super-fast” progress to the clinic. “Once you have it, boy, everything just lines up,” he says. And although the end of the PCSK9 story has yet to be written — the advanced clinical trials now under way could still be derailed by unexpected side effects — it holds a valuable lesson for genomic research. The key discovery about PCSK9‘s medical potential was made by researchers working not only apart from the prevailing scientific strategy of genome research over the past decade, but with an almost entirely different approach.

As for Tracy, who lives in the southern part of Dallas County, the implications of her special genetic status have become clear. “I really didn’t understand at first,” she admits. “But now I’m watching ads on TV [for cholesterol-lowering drugs], and it’s like, ‘Wow, I don’t have that problem’.”

A heart problem

Cardiovascular disease is — and will be for the foreseeable future, according to the World Health Organization — the leading cause of death in the world, and its development is intimately linked to elevated levels of cholesterol in the blood. Since their introduction, statin drugs have been widely used to lower cholesterol levels. But Jan Breslow, a physician and geneticist at Rockefeller University in New York, points out that up to 20% of patients cannot tolerate statins’ side effects, which include muscle pain and even forgetfulness. And in many others, the drugs simply don’t control cholesterol levels well enough.

The search for better treatments for heart disease gained fresh impetus after scientists published the draft sequence of the human genome in 2001. In an effort to identify the genetic basis of common ailments such as heart disease and diabetes, geneticists settled on a strategy based on the ‘common variant hypothesis’. The idea was that a handful of disease-related versions (or variants) of genes for each disease would be common enough — at a frequency of roughly 5% or so — to be detected by powerful analyses of the whole genome. Massive surveys known as genome-wide association studies compared the genomes of thousands of people with heart disease, for example, with those of healthy controls. By 2009, however, many scientists were lamenting the fact that although the strategy had identified many common variants, each made only a small contribution to the disease. The results for cardiovascular disease have been “pretty disappointing”, says Daniel Steinberg, a lipoprotein expert at the University of California, San Diego.

Single-minded: Helen Hobbs and Jonathan Cohen’s approach to heart-disease genetics yielded a target for drugs that could compete with statins.MISTY KEASLER/REDUX/EYEVINE

More than a decade earlier, in Texas, Hobbs and Cohen had taken the opposite tack. They had backgrounds in Mendelian, or single-gene, disorders, in which an extremely rare variant can have a big — often fatal — effect. They also knew that people with a particular Mendelian disorder didn’t share a single common mutation in the affected gene, but rather had a lot of different, rare mutations. They hypothesized that in complex disorders, many different rare variants were also likely to have a big effect, whereas common variants would have relatively minor effects (otherwise natural selection would have weeded them out). “Jonathan and I did not see any reason why it couldn’t be that rare variants cumulatively contribute to disease,” Hobbs says. To find these rare variants, the pair needed to compile detailed physiological profiles, or phenotypes, of a large general population. Cohen spoke of the need to “Mendelize” people — to compartmentalize them by physiological traits, such as extremely high or low cholesterol levels, and then look in the extreme groups for variations in candidate genes known to be related to the trait.

The pair make a scientific odd couple. Hobbs, who trained as an MD, is gregarious, voluble and driven. Cohen, a soft-spoken geneticist from South Africa, has a laid-back, droll manner and a knack for quantitative thinking. In 1999, they set out to design a population-based study that focused on physical measurements related to heart disease. Organized with Ronald Victor, an expert on high blood pressure also at UT Southwestern, and funded by the Donald W. Reynolds Foundation in Las Vegas, Nevada, the Dallas Heart Study assembled exquisitely detailed physiological profiles on a population of roughly 3,500 Dallas residents2. Crucially, around half of the participants in the study were African Americans, because the researchers wanted to probe racial differences in heart disease and high blood pressure. The team measured blood pressure, body mass index, heart physiology and body-fat distribution, along with a battery of blood factors related to cholesterol metabolism — triglycerides, high-density lipoprotein (HDL) cholesterol and LDL cholesterol. In the samples of blood, of course, they also had DNA from each and every participant.

As soon as the database was completed in 2002, Hobbs and Cohen tested their rare-variant theory by looking at levels of HDL cholesterol. They identified the people with the highest (95th percentile) and lowest (5th percentile) levels, and then sequenced the DNA of three genes known to be key to metabolism of HDL cholesterol. What they found, both in Dallas and in an independent population of Canadians, was that the number of mutations was five times higher in the low HDL group than in the high group3. This made sense, Cohen says, because most human mutations interfere with the function of genes, which would lead to the low HDL numbers. Published in 2004, the results confirmed that rare, medically important mutations could be found in a population subdivided into extreme phenotypes.

Armed with their extensive database of cardiovascular traits, Hobbs and Cohen could now dive back into the Dallas Heart Study whenever they had a new hypothesis about heart disease and, as Cohen put it, “interrogate the DNA”. It wasn’t long before they had an especially intriguing piece of DNA at which to look.

The missing link

In February 2003, Nabil Seidah, a biochemist at the Clinical Research Institute of Montreal in Canada, and his colleagues reported the discovery of an enigmatic protein4. Seidah had been working on a class of enzymes known collectively as proprotein convertases, and the researchers had identified what looked like a new member of the family, called NARC-1: neural apoptosis-regulated convertase 1.

“We didn’t know what it was doing, of course,” Seidah says. But the group established that the gene coding the enzyme showed activity in the liver, kidney and intestines as well as in the developing brain. The team also knew that in humans the gene mapped to a precise genetic neighbourhood on the short arm of chromosome 1.

That last bit of geographical information pointed Seidah to a group led by Catherine Boileau at the Necker Hospital in Paris. Her team had been following families with a genetic form of extremely high levels of LDL cholesterol known as familial hypercholesterolaemia, which leads to severe coronary artery disease and, often, premature death. Group member Marianne Abifadel had spent five fruitless years searching a region on the short arm of chromosome 1 for a gene linked to the condition. When Seidah contacted Boileau and told her that he thought NARC-1 might be the gene she was looking for, she told him, “You’re crazy”, Seidah recalls. Seidah bet her a bottle of champagne that he was correct; within two weeks, Boileau called back, saying: “I owe you three bottles.”

“The PCSK9 story is a terrific example of an up-and-coming pattern of translational research.”

In 2003, the Paris and Montreal groups reported that the French families with hypercholesterolaemia had one of two mutations in this newly discovered gene, and speculated that this might cause increased production of the enzyme5. Despite Seidah’s protests, the journal editors gave both the gene and its protein product a new name that fit with standard nomenclature: proprotein convertase subtilisin/kexin type 9, or PCSK9. At around the same time, Kara Maxwell in Breslow’s group at Rockefeller University6 and Jay Horton, a gastroenterologist at UT-Southwestern7 also independently identified the PCSK9 gene in mice and revealed its role in a previously unknown pathway regulating cholesterol8.

The dramatic phenotype of the French families told Hobbs that “this is an important gene”. She also realized that in genetics, mutations that knock out a function are much more common than ones that amplify function, as seemed to be the case with the French families. “So immediately I’m thinking, a loss-of-function mutation should manifest as a low LDL level,” she says. “Let’s go and see if that’s true.”

Going to extremes

Hobbs and Cohen had no further to look than in the extreme margins of people in the Dallas Heart Study. In quick order, they identified the highest and lowest LDL readings in four groups: black women, black men, white women and white men. They then resequenced the PCSK9 gene in the low-cholesterol groups, looking for mutations that changed the make-up of the protein.

They found seven African Americans with one of two distinct ‘nonsense’ mutations in PCSK9 — mutations that essentially aborted production of the protein. Then they went back and looked for the same mutations in the entire population. Just 2% of all black people in the Dallas study had either of the two PCSK9 mutations — and those mutations were each associated with a 40% reduction of LDL cholesterol in the blood9. (The team later detected a ‘missense mutation’ in 3% of white people, which impaired but did not entirely block production of the protein.) The frequency of the mutations was so low, Hobbs says, that they would never have shown up in a search for common variants.

When Hobbs and Cohen published their findings in 2005, they suggested that PCSK9 played a crucial part in regulating bad cholesterol, but said nothing about whether the mutations had any effect on heart disease. That evidence came later that year, when they teamed up with Eric Boerwinkle, a geneticist at the University of Texas Health Science Center in Houston, to look forPCSK9 mutations in the Atherosclerosis Risk in Communities (ARIC) study, a large prospective study of heart disease that had been running since 1987. To experts such as Steinberg, the results10 — published in early 2006 — were “mind-blowing”. African Americans in ARIC who had mutations in PCSK9 had 28% less LDL cholesterol and an 88% lower risk of developing heart disease than people without the mutations. White people with the less severe mutation in the gene had a 15% reduction in LDL and a 47% reduced risk of heart disease.

How did the gene exert such profound effects on LDL cholesterol levels? As researchers went on to determine11, the PCSK9 protein normally circulates in the bloodstream and binds to the LDL receptor, a protein on the surface of liver cells that captures LDL cholesterol and removes it from the blood. After binding with the receptor, PCSK9 escorts it into the interior of the cell, where it is eventually degraded. When there is a lot of PCSK9 (as in the French families), there are fewer LDL receptors remaining to trap and remove bad cholesterol from the blood. When there is little or no PCSK9 (as in the black people with mutations), there are more free LDL receptors, which in turn remove more LDL cholesterol.

“We didn’t understand why everybody wasn’t doing what we were doing.”

The UT-Southwestern group, meanwhile, went back into the community looking for family members who might carry additional PCSK9 mutations. In September 2004, Gilbert, the nurse known as ‘the cholesterol lady’ in south Dallas because of her frequent visits, knocked on the door of Sharlayne Tracy’s mother, an original member of the Dallas Heart Study. Gilbert tested Tracy, as well as her sister, brother and father. “They tested all of us, and I was the lowest,” Tracy says. Zahid Ahmad, a doctor working with Hobbs at UT-Southwestern, was one of the first to look at Tracy’s lab results. “Dr Zahid was in awe,” Tracy recalled. “He said, ‘You’re not supposed to be so healthy!’.”

It wasn’t just that her LDL cholesterol measured 14. As a person with two dysfunctional copies of the gene — including a new type of mutation — Tracy was effectively a human version of a knockout mouse. The gene had been functionally erased from her genome, and PCSK9 was undetectable in her blood without any obvious untoward effects. The genomics community might have been a little slow to understand the significance, Hobbs says, “but the pharmaceutical companies got it right away”.

The next statin?

This being biology, however, the road to the clinic was not completely smooth. The particular biology of PCSK9 has so far thwarted efforts to find a small molecule that would interrupt its interaction with the LDL receptor and that could be packaged in a pill. But the fact that the molecule operates outside cells means that it is vulnerable to attack by monoclonal antibodies — one of the most successful (albeit most expensive) forms of biological medicine.

The results of early clinical trials have caused a stir. Regeneron Pharmaceuticals of Tarrytown, New York, collaborating with Sanofi, published phase II clinical-trial results12 last October showing that patients with high LDL cholesterol levels who had injections every two weeks of an anti-PCSK9 monoclonal antibody paired with a high-dose statin saw their LDL cholesterol levels fall by 73%; by comparison, patients taking high-dose statins alone had a decrease of just 17%. Last November, Regeneron and Sanofi began to recruit 18,000 patients for phase III trials that will test the ability of their therapy to cut cardiovascular events, including heart attacks and stroke. Amgen of Thousand Oaks, California, has also launched several phase III trials of its own monoclonal antibody after it reported similarly promising results13. Among other companies working on PCSK9-based therapies are Pfizer headquartered in New York, Roche based in Basel, Switzerland, and Alnylam Pharmaceuticals of Cambridge, Massachusetts. (Hobbs previously consulted for Regeneron and Pfizer, and now sits on the corporate board of Pfizer.)

Not everyone is convinced that a huge market awaits this class of cholesterol-lowering drugs. Tony Butler, a financial analyst at Barclays Capital in New York, acknowledges the “beautiful biology” of the PCSK9 story, but wonders if the expense of monoclonal drugs — and a natural reluctance of both patients and doctors to use injectable medicines — will constrain potential sales. “I have no idea what the size of the market may be,” he says.

“Everything hinges on the phase III side effects,” says Steinberg. So far, the main side effects reported have been minor, such as reactions at the injection site, diarrhoea and headaches. But animal experiments have raised potential red flags: the Montreal lab reported in 2006 that knocking out the gene in zebrafish is lethal to embryos14. That is why the case of Tracy was “very, very helpful” to drug companies, says Hobbs. Although her twin mutations have essentially deprived her of PCSK9 throughout her life, doctors have found nothing abnormal about her.

That last point may revive a debate in the cardiology community: should drug therapy to lower cholesterol levels, including statins and the anti-PCSK9 medicines, if they pan out, be started much earlier in patients than their 40s or 50s? That was the message Steinberg took from the people withPCSK9 mutations in the ARIC study — once he got over his shock at the remarkable health effects. “My first reaction was, ‘This must be wrong. How could that be?’And then it hit me — these people had low LDL from the day they were born, and that makes all the difference.” Steinberg argues that cardiologists “should get off our bums” and reach a consensus about beginning people on cholesterol-lowering therapy in their early thirties. But Breslow, a former president of the American Heart Association, cautions against being too aggressive too soon. “Let’s start out with the high-risk individuals and see how they do,” he says.

Not long after Hobbs and Cohen published their paper in 2006, they began to get invited to give keynote talks at major cardiology meetings. Soon after, the genetics community began to acknowledge the strength of their approach. In autumn 2007, then-NIH director Zerhouni organized a discussion at the annual meeting of the institutes’ directors to raise the profile of the rare-variant approach and contrast it with genome-wide studies. “Obviously, the two approaches are opposed to each other, and the question was, what was the relative value of each?” says Zerhouni. “I thought the PCSK9 story was a terrific example of an up-and-coming pattern of translational research” — indeed, he adds, “a harbinger of things to come”.

Hobbs and Cohen might not have found their gene if they had not had a hunch about where to look, but improved sequencing technology and decreasing costs now allow genomicists to incorporate the rare variant approach and to mount large-scale sweeps in search of such variants. “Gene sequencing is getting cheap enough that if there’s another gene like PCSK9 out there, you could probably find it genome-wide,” says Jonathan Pritchard, a population biologist at the University of Chicago, Illinois.

“What was amazing to us,” says Hobbs, “was that the genome project was spending all this time, energy, effort sequencing people, and they weren’t phenotyped, so there was no potential for discovery. We didn’t understand, and couldn’t understand, why everybody wasn’t doing what we were doing. Particularly when we started making discoveries.”

SOURCE:

Nature 496, 152–155 (11 April 2013) doi:10.1038/496152a

References
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  2. Victor, R. G. et al. Am. J. Cardiol. 93, 1473–1480 (2004).

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  3. Cohen, J. C. et al. Science 305, 869–872 (2004).

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  4. Seidah, N. G. et al. Proc. Natl Acad. Sci. USA 100, 928–933 (2003).

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  5. Abifadel, M. et al. Nature Genet. 34, 154–156 (2003).

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  6. Maxwell, K. N., Soccio, R. E., Duncan, E. M., Sehayek, E. & Breslow, J. L. J. Lipid Res. 44,2109–2119 (2003).

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  7. Horton, J. D. et al. Proc. Natl Acad. Sci. USA 100, 12027–12032 (2003).

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  8. Maxwell, K. N. & Breslow, J. L. Proc. Natl Acad. Sci. USA 101, 7100–7105 (2004).

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  9. Cohen, J. et al. Nature Genet. 37, 161–165 (2005).

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  10. Cohen, J. C., Boerwinkle, E., Mosley, T. H. Jr & Hobbs, H. H. N. Engl. J. Med. 354, 1264–1272(2006).

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  11. Horton, J. D., Cohen, J. C. & Hobbs, H. H. J. Lipid Res. 50, S172–S177 (2009).

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  12. Roth, E. M., McKenney, J. M., Hanotin, C., Asset, G. & Stein, E. A. N. Engl. J. Med. 367,1891–1900 (2012).

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Author information

Affiliations

  1. Stephen S. Hall is a science writer in New York who also teaches public communication to graduate students in science at New York University.

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Reporter: Aviva Lev-Ari, PhD, RN

Will ‘gamifying’ drug R&D win more than Facebook fans for Boehringer?

By Tracy Staton, FiercePharma, August 22, 2012

Lots of computer games enlist players in quests to save the world. But how many would-be saviors are developing drugs? We can’t think of any–until now. Boehringer Ingelheim is on the verge of launching Syrum, a Facebook game of test tubes and titrations, not crossbows and assault rifles.

 “The health of the world is in your hands,” Boehringer’s director of digital, John Pugh, tells PSRK, in what could be a voice-over for a YouTube promo video for the game. “And you’re the only one who can save it.”

 Players have to solve a problem–e.g., a pandemic–via drug development, all the way from early discovery through clinical trials and launch. They can enlist help from Facebook friends, and advance in the game by checking into locations via the social network’s mobile app. “It wasn’t built with a view to being an educational platform,” Pugh says. “It’s very much a game which is meant to be engaging and entertaining … In the same way that Farmville doesn’t just appeal to people who like farms, Syrum isn’t just for people who like the pharmaceutical industry.”

But it was education that drew Pugh and his team into the project; as he points out for PSFK, the industry does a lot of it, whether that’s “educating” doctors about products, or teaching patients how to take their meds properly. Just because the game isn’t designed as an educational platform doesn’t mean it can’t educate, in a stealthy, backhanded way.

Syrum has been in development for two years. On Sept. 13, Boehringer will unveil a beta version at a London conference, aiming to get feedback from players for future iterations. “[T]he game will grow and evolve as more people play it,” Pugh says.

He also says Syrum is a “very unique offering from a highly regulated industry.” True. Whether it will remain unique depends, in part, on how Syrum actually fares. Will it attract a following? And if it does, will gamification of drug development actually benefit Boehringer’s business? Image? Relations with patients? Pharma’s social media advocates (and skeptics) will be watching.

John Pugh, Director of Digital for Boehringer Ingelheim, talks about driving innovation in his large organization with the forthcoming game Syrum – which he will launch at PSFK CONFERENCE LONDON on September 13.
 
 
 
 
By Tim Ryan on August 21, 2012.
  • John Pugh is the Director of Digital for Boehringer Ingelheim GmbH – a group of pharmaceutical companies that specialize in research and development for prescription medicine products. He spoke to PSFK recently about driving innovation in a large organization with his forthcoming game Syrum – which he will launch at PSFK CONFERENCE LONDON on September 13.

Your company has a new game, Syrum. What is it – and why is a pharmaceutical company like Boehringer Ingelheim involved in it?

What really sparked my interest in the potential of gaming is that a lot of what we do in pharma is around educating and teaching people; whether that’s teaching doctors about specific products, educating the general public and patients about diseases and healthy ways to live, or teaching people how to take their medication.

Gaming seems to be a useful way and effective way for us to do that. I basically began the journey to try and work out what I could do in gaming that wasn’t an arcade or platform based game — but was something a bit more immersive.

Syrum has been in development for at least two years. At the beginning, we called in lots of experts from different industries, different locations in countries, and with different skill sets. We had various leaders, from specialized futurologists to branding experts, from pharma people to gaming people, and even young entrepreneurs who’d made a million dollars by the age of 17.

We really worked together to create a vision of the future, and one of the strong things that came through was the influence of gaming and gamification.

After two years of hard work, the result is that we are about to launch Syrum, the pharmaceutical industry’s first social game.

syrum-boehringer-ingelheim

Can you tell us a little more about the gameplay in Syrum?

Syrum is a social game. The health of the world is in your hands, and you’re the only one who can save it. In each chapter, you have to solve a particular problem, which could be a disease or a pandemic that is sweeping the world. The player’s goal is to discover cures, create a stable drug, and then create a clinical trial so that you can launch the drug and cure the disease.

It’s a social game, because you can collaborate with friends or other people, and you can give them gifts, even headhunt their staff. As the game progresses, it gets more and more complicated.

syrum-boehringer-ingelheim-game

What do you think people will get out of it?

First, it’s a fun game. It wasn’t built with a view to being an educational platform or anything like that. It’s very much a game which is meant to be engaging and entertaining to play. In the same way that Farmville doesn’t just appeal to people who like farms, Syrum isn’t just for people who like the pharmaceutical industry. It’s for anyone to play.

It’s built on Facebook because that’s the world’s biggest gaming platform. What we really wanted to do was try to use a lot of the features of Facebook. For example we leverage Facebook Places, a service where people can check into locations. It’s really bridging that offline/online world. Places helps players market the products they make. Wherever the players check in through the Facebook mobile app, that data gets integrated into the game and you get rewarded accordingly.

syrum-boehringer-ingelheim-game

When will it be available?

September 13. We are taking a Silicon Valley approach, where we know we have got a really good game that’s stable but we’ll launch a beta version. We really want to make it so that we get lots of feedback from the people who are playing.

We’re offering rewards and prizes for people to give feedback so that we can really create the duration of the game, and develop it, and have more of a crowdsourced collaborative effort to develop the future stages of it, so the game will grow and evolve, as more people play it. This is a very unique offering from a highly regulated industry.

Can we finish by understanding your role within the organization – and how you drive change.

My job is anything which is connected to digital, so that includes apps, mobile, websites, gaming, crowdsourcing, and so forth. Our goal is to find applications for all of that. I bring to this company new ideas and I inspire them, educate them, cajole them, prod them to try new things, particularly in digital. I want BI to stretch out beyond the traditional marketing activities because in pharmaceuticals, and particularly at Boehringer, we’re still very traditional in what we do.

Thanks John!

Come see John talk about the launch of Syrum at PSFK CONFERENCE LONDON.

Syrum / @johnpugh / Boehringer Ingelheim

Click the banner below to purchase tickets and find additional information about this year’s event.

 

via PSFK: http://www.psfk.com/2012/08/pharma-social-game-psfk-london.html#ixzz24IgR5ZEm

http://www.psfk.com/2012/08/pharma-social-game-psfk-london.html

How Sanofi Is Writing The Social Media Rules For Big Pharma Without Running Afoul Of The FDA

BY BEN PAYNTER

 | 

AUGUST 20, 2012

After a Facebook PR meltdown two years ago, Sanofi has emerged as a social media leader with a robust community for diabetics. Here’s how they are writing #TheRules while the FDA catches up.

About This Series

#therules

Follow Fast Company’s roadmap to social media: surefire rules, data, and expert wisdom guaranteed to show why this market is completely unpredictable.READ MORE

The biggest challenge to treating patients with diabetes isn’t doling out medications, it’s making sure that people control their habits. Poor diet and lack of exercise generally create complications with the disease. To combat the problems, researchers in the diabetes division of Sanofi US took an unusual step for Big Pharma: they went social, jumping into online networking with a Facebook page, Twitter presence, and eventually three different engagement platforms.

“Treatment is an important aspect to blood sugar management, but it isn’t the only aspect,” says Laura Kolodjeski, Sanofi’s diabetes community manager, who has become the virtual face of the company. “There is a huge community of people already that live with diabetes and are connecting and sharing [online] to improve each other’s experience with the disease.”

 

Laura Kolodjeski

 

Sanofi now helps direct and police those interactions online. The company won’t release total visitor numbers, but it has about 4,000 followers on Facebook and another 4,000 on Twitter, all of whom are sharing links to broader content. And for better or worse that community is going to grow: About 8 percent of Americans or roughly 26 million people have diabetes, and the Centers for Disease Control predicts that as many as one third of us could have the disease by 2050.

But the social frontier is potentially prickly for Sanofi because the FDA has not yet written the rules about how pharmaceuticals are allowed to engage with potential customers and patients. The only guidelines came out in a December 2011 advisory statement declaring that while allowing virtual comments about things like off-label uses isn’t technically illegal, it’s shady territory; basically, pontificate at your own risk. “We are working on the area and it’s something we feel is important but we don’t have a specific timeline right now,” says Ernest Voyard, senior regulatory council at the FDA’s Office of Prescription Drug Promotion.

For Sanofi, drawing up their own social media strategy is also a defensive move: In 2010, the company’s cancer division suffered a PR nightmare after a patient, who claimed to have experienced permanent hair loss from one of their treatment drugs, posted complaints and photos on that group’s unmonitored Facebook page. John Mack, the editor of Pharma Marketing News, which tracks shifts in the pharmaceutical industry, says such hits are common anytime you try to pioneer a new space. “They’ve had some rough times, but they are learning a lot,” he adds.

Mack considers Sanofi a leader in the category, especially compared with the offerings from other companies. Diabetes juggernaut Novo Nordisk sponsors IndyCar driver Charlie Kimball to tweet @racewithinsulin, including when he injects with their products. And Pfizer’s ThinkScienceNow blog about developments and advances in research is wonky but not exactly customer friendly.

Sanofi has created a template they hope will eventually be deemed both acceptable to the FDA and cool for customers. The lessons they’ve learned in the last two years is a valuable addition to The Social Media Roadmap from our current issue.

Be Transparent

When she took over as social media director, one of the first things Kolodjeski did was post a bio with a photo of herself online at DiscussDiabetes to show who was moderating. She also disclosed that she wasn’t diabetic. Why? To build trust, the kind community members might not have for a faceless company run by mostly non-diabetics. The message: “If Laura is going to work every day to solve [issues] on our behalf, then others must be doing the same,” Kolodjeski says.

Rather than just explain the rules of their forums in a jargon-y “terms of use” agreement Kolodjeski also tapped Mark Gaydos, head of the company’s U.S. regulatory affairs for marketed products division, to do a Q&A about how the sites would function. For instance, anytime someone on the site mentions a product, they are technically promoting it, so there needs to be fair balance of potential benefits and risks explained alongside that per FDA guidelines. That means many posts get quarantined internally before posting, so the company can add additional links or annotations to more information. Sanofi only wants to allow discussion of FDA-approved uses for products–any mention of possible side-benefits or bonuses from tweaking the usual dose regimen is prohibited. To make sure everything meets these requirements, there is often a delay–sometimes up to 24 hours–between when users make comments and those comments become publicly visible.

To explain their business interest, Kolodjeski also interviewed Dennis Urbaniak, the head of the company’s U.S. diabetes business unit to explain what he calls the “360-degree partner” principle–an effort to inspire others to talk more and tap into that as a focus group for new ideas.

Let Users Shape Expansion

Sanofi launched their diabetes Facebook and Twitter handles in September 2010 mainly to offer news updates about the company and its offerings. On Facebook, any clinical questions were directed to a separate tab and often answered privately. On Twitter, medical concerns were covered via direct message. What was missing was a way to collect various poster’s lifestyle tips and inspirational messages all in one place. In January 2011, the company launched DiscussDiabetes to address that. They also run their own stories about successes, including highlights from A1C Champions, another company sponsored group of diabetics who have maintain the best or “A1C” target range of blood sugar levels.

By March of this year, the company took a look at the discussions that were being generated and realized that terms like A1C weren’t actually as universally understood as they once thought. To speed that learning curve, they launched Diabetepedia, which provides both simple definitions and links to other sites showing how terms are actually used in other online conversations.

The final step: After noticing how activity at Diabetepedia was spiking, Sanofi launched another site collecting lots of the content they were already linking to all in one place. The DX, which launched at the end of May, hosts daily dispatches by both Kolodjeski and stable of already popular bloggers (none of whom are paid directly) that include everything from a diabetes related comic strip to mommy blogs for parents with diabetic kids. “We really allowed the community to help identify what might be useful to them and where they might go next,” Kolodjeski says.

Give Users Even More Control

The medical glossary at Diabetepedia doesn’t just provide standard definitions to complex terminology, users are encouraged to submit their own entries, creating a sort of slang dictionary that makes complicated stuff more relatable to newcomers. For instance, glucoaster: that’s shorthand for “a rollercoaster of blood glucose levels, with blood sugar lows followed by blood sugar highs.” User contributions have helped the database grow by 30 percent to include more than 150 terms, all of which make it easier to users themselves to better convey thoughts in future postings.

The company also considers each media outpost an exclusive “channel,” which means there is lots of cross-posting of content from different platforms to make sure users who only tune into one place are being best served. “We certainly have people that overlap but for the most part people have selected which channel they feel represented by and communicate through,” Kolodjeski says. But at each stop, the company still tries to crowdsource bigger ideas.

This year, they asked users to help set priorities for the company’s annual Data Design Diabetes Innovation Challenge, which asks individuals, businesses and non-profits to create new initiatives for using big data to help others struggling with the disease. To help brainstorm for that, Sanofi’s social media troop was given the chance to visit a competition homepage and answer questions about what aspects of life with the disease might be consistently overlooked or ignored. Their answers were used to shape a final guideline for contestants that solutions must address the overall wellness and family life of patients, not just symptom mediation. The winner: a program created by the n4a Diabetes Care Center that matches people with certain cost or risk profiles directly to the services they might need to slow the progression or expense of the disease. Mood problems can be addressed by better disease management, hopefully cutting into the 18 percent of all diabetics who require hospitalization each year.

After realizing just how open users are to sharing and connecting, Sanofi also launched their own new product, the iBGStar, a personal blood glucose monitor that plugs directly into an iPhone or iPod Touch with an app that saves data and maps correlations between blood sugar levels and meal times, carb and sugar intake, and physical activity. Users can share results with their family or email them to health care providers. But the product, which hit the market in May 2012, wasn’t just inspired by early community actions; ensuing reviews and comments in their own forums will help refine future updates. “It’s a big hit with the online community,” Kolodjeski says. “It’s also given us a great opportunity to prove back to them that if we hear someone comment about something, we have the ability to engage in a public manner.”

Correction: An earlier version of this article said that iBGStar came on the market in 2011, it was released in May 2012.

http://www.fastcompany.com/3000457/how-sanofi-writing-social-media-rules-big-pharma-without-running-afoul-fda

Lilly to develop company-wide social media strategy

11 Jul 2012

 
Nearly two years after launching its first major foray into the world of social media in the shape of its LillyPad corporate blog, Eli Lilly is developing a company-wide social media strategy.

Lilly has so far had strict rules about who can use social media on behalf of the company, authorising just a handful of people in corporate communications and government affairs, but now wants to empower other departments to do so.

“There are a lot of parts of the company that are getting interested in social media so I’m working on a strategy that will keep these aligned with one another,” Lilly’s director of corporate communications Greg Kueterman told SMI’s Social Media in the Pharmaceutical Industry conference on Monday.

“We don’t want to have eight different social media platforms that all look and sound very different from one another. So we’re going to try and do something where they all have their own identity but are still consistent within the company.”

Kueterman acknowledged LillyPad, launched September 2010, and the company’s Campaign For Modern Medicines, a US health policy initiative Lilly founded last year that uses Twitter, Facebook and YouTube, were set up “before we had a full blown strategy”.

“But sometimes that is important,” he said. “Because you have to know what you have, before you can make it even bigger.”

The company’s Clinical Open Innovation team, a group working to improve the drug development process, also began using social media earlier this year, with a blog and Twitter account.

The next stage for Lilly will be to continue its expansion of LillyPad (as previewed herein March), following the launch in May of a Canadian version of the corporate blog.

“We’ve started to go global with LillyPad and we’re working with a number of our affiliates to do this. Lilly Canada has been the first one out of the box to do that and they’re off to a nice start,” Kueterman said.

Discussions are underway with the company’s European affiliates in the UK and Belgium along with its operations in Mexico. “Hopefully some of those are going to be launching this year, although we don’t have firm dates yet,” Kueterman said.

“We’re excited that this is a programme that’s going to start picking up momentum. Looking ahead there are still things that we can do much better. I’m never really satisfied with the way things are going with LillyPad – I’m happy, because I think we’re doing things the right way, but I also believe that we can be even more proactive than we are.”

• Links to Lilly’s social media presences can be found in the Pharma Social Media Directory‘s blogsTwitterFacebook and YouTube sections 

http://www.pmlive.com/digital_intelligence_blog/archive/2012/jul_2012/lilly_to_develop_company-wide_social_media_strategy

What Else Can We (Really) Do?

by Greg Kueterman 07/10/12 


On Monday, I had the pleasure of presenting Lilly’s social media history and strategy at a conference in London. The history part was easy: LillyPad — our first major platform — has been around for 22 months. We’re not experiencing the Terrible Twos just yet, but we’ve still got plenty to learn.

The London audience — consisting of European and U.S. communicators and marketing experts at the Social Media for Pharmaceutical Industry conference. — warmly embraced our strategy of addressing issues such as public policy and medical innovation. And the reception was not unusual. Over the last two years, we’ve talked LillyPad in live settings from London to New York to Indianapolis to San Francisco — and our peers typically offer two thumbs up for the good work.

For that, we are grateful. But it’s a good reminder about a couple questions we need to ask more often:

What else can we be doing? What else should we be doing?

As our loyal readers, you know what we offer — and you know what you need to become more informed. We would love to hear more from you: the good, the bad, and the ugly. We’re always looking to enhance LillyPad, and we’ve taken a lot of steps in recent months to do so (more video, more guest blogs, and — we think — clearer, more conversational writing). And while we will remain a non-product communications vehicle, we’re open to any and all ideas that make your LillyPad experience even better.

From London (where I’ve seen more rain in three days than my backyard has seen in two months) thanks for reading!

http://lillypad.lilly.com/entry.php?id=1736

 

 

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