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Here's a slide from http://www.secinfo.com/dsvr4.tgP9.b.htm and Merck guided for an NDA filing for MK-0524A in 2012.
Indeed a long term CV outcomes study is being planned to begin in 2010.
Another small vascular imaging study, this time from Johns Hopkins, whose heart experts called the early halt of the ARBITER-HALTS 6 study - "premature"
Public release date: 18-Nov-2009
Contact: David March
dmarch1@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
Vitamin B niacin offers no extra benefit to statin therapy in seniors already diagnosed with CAD
Blood cholesterol levels improved, but arteries do not show it
The routine prescription of extended-release niacin, a B vitamin (1,500 milligrams daily), in combination with traditional cholesterol-lowering therapy offers no extra benefit in correcting arterial narrowing and diminishing plaque buildup in seniors who already have coronary artery disease, a new vascular imaging study from Johns Hopkins experts shows.
In tests on 145 Baltimore-area men and women with existing atherosclerosis, all over age 65, researchers found that after 18 months of drug therapy, reductions in arterial wall thickness were measurably no different between the half who took dual niacin-statin therapy and the rest who remained on statin therapy alone.
The results were the same whether they took any one of the three leading statin medications: atorvastatin (Lipitor), simvistatin (Zocor) or rosuvastatin (Crestor). Seniors on dual drug therapy had an average 5.4 cubic millimeter per month scale back in plaque buildup in the main neck artery, while those taking just a cholesterol-lowering statin medication came down by 4 cubic millimeters per month, a difference that researchers say is not statistically significant.
The team will present its findings Nov. 18 at the American Heart Association's (AHA) annual Scientific Sessions in Orlando.
According to senior study investigator and Johns Hopkins cardiologist João Lima, M.D., the lack of any discernible advantage occurred despite promising gains in bad (LDL) and good (HDL) blood cholesterol levels in those taking vitamin B niacin. Results showed that in the group taking both niacin and a statin, blood levels of LDL-cholesterol fell 5 percent more than in the group taking only statin medications. And levels of HDL jumped 14 percent more than in the statin-only group.
"Our findings tell us that improved cholesterol levels from taking combination vitamin B niacin and statin therapy do not necessarily translate into observable benefits in reversing and stalling carotid artery disease," says Lima, a professor of medicine and radiology at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute. "This does not mean that niacin therapy may not have other cardiovascular benefits, but any such benefits are independent of reducing the amount of plaque buildup and patients should be aware of that."
"Our recommendation to physicians is that current national treatment guidelines, which recommend mainly statin therapy tailored to the severity of atherosclerosis for preventing arteries from reclogging and narrowing, appear to be sufficient and accurate for physicians and patients to follow," says Lima.
However, Lima cautions that an ongoing national study of the long-term vascular benefits of dual therapy and whether extended-release niacin, also known as nicotinic acid, lowers death rates from heart disease should provide more definitive data. Hopkins is participating in that research, as well. He also notes that extended-releases niacin used in this study is a prescription medication, and that it is not sold over the counter like many other vitamin B products.
"The real value in initially studying this particular group of people is that these seniors are the ones who I am most likely to see in the hospital, the group most vulnerable to coronary artery disease and most at risk of suffering an arterial blockage, heart attack, or stroke," says lead study investigator Christopher Sibley, M.D. Nearly 17 million American adults are estimated to have some form of coronary artery disease, resulting in more than 400,000 deaths each year.
"Practically speaking, carotid MRI scans are an option to assess the risk of patients based on the amount of plaque in their arteries, to better determine who needs aggressive statin therapy and to monitor how well they respond to treatment," says Sibley, an adjunct assistant professor at Johns Hopkins, as well as a staff clinician at the National Institutes of Health Clinical Center.
All study participants had one or more preexisting cardiovascular health issues, such as a previous heart attack, stroke, coronary artery bypass grafting to resupply blood to the heart, severe chest pain, or angioplasty with the placement of wire stents to keep arteries open.
At the start of the study, participants received an MRI scan of their carotid artery, and again every six months thereafter. The four sets of carotid images provided what Sibley says is "an important window" into what is going on in the body's network of veins and arteries. He notes that the neck artery is important not just because it serves as the main blood supply to the brain, but also because narrowing in the carotid artery reflects the risk of future heart attack.
Sibley says that the team has begun to analyze blood samples collected as part of the study, searching for chemicals that might also signal a change in arterial plaque buildup and progressive arterial narrowing.
I believe the MK-0524A trial is expected to complete earlier than 2013 - by Jan 2012.
More Brilinta data:
Astra drug shows faster onset/offset than Plavix
http://www.reuters.com/article/rbssHealthcareNews/idUSN189816320091118
* Brilinta onset greater at 0.5, 1, 2, 4, 8 and 24 hours
* At 2 hrs over 50 pct effect seen in 98 pct on Brilinta
* Brilinta effect 2 days less to wear off than Plavix
By Bill Berkrot and Ransdell Pierson
ORLANDO, Fla.,, Nov 18 (Reuters) - AstraZeneca's (AZN.L: Quote, Profile, Research, Stock Buzz) experimental Brilinta blood clot preventer begins working much faster than widely-used Plavix and the intended effect wears off more quickly, according to data from a mid-stage study presented on Wednesday.
Each of those effects is extremely desirable depending on the type of procedure a heart patient is in need of, and could give AstraZeneca an important marketing edge when its drug begins competing with Plavix, now the standard of care with annual sales of about $9 billion for Bristol-Myers Squibb Co(BMY.N: Quote, Profile, Research, Stock Buzz) and Sanofi-Aventis (SASY.PA: Quote, Profile, Research, Stock Buzz).
Analysts see Brilinta as a potential multibillion-dollar a year seller for AstraZeneca, which plans to file an application seeking U.S. approval later this year.
Brilinta showed greater inhibition of platelet aggregation, or clumping, than Plavix at half an hour, one hour, two, four eight and 24 hours after patients received the initial treatment dose, according to data presented at the American Heart Association scientific meeting in Orlando.
In a large Phase III trial released earlier this year, Brilinta demonstrated superiority to Plavix in preventing heart attacks and death with no increased risk of major bleeding, alleviating concerns that safety might be compromised by higher efficacy. Bleeding is the major source of worry with drugs that work by keeping blood cells called platelets from clumping together.
The Phase II onset/offset data unveiled Wednesday was designed to give better understanding of how Brilinta, known chemically as ticagrelor, works in the body.
At two hours after initial dosing, 98 percent of Brilinta patients achieved greater than 50 percent platelet clumping inhibition compared with 31 percent of those on Plavix -- a result deemed to be highly statistically significant.
And 90 percent of those on Brilinta reached greater than 70 percent anti-clotting action versus just 16 percent in the Plavix group at two hours.
Speed of action is beneficial as these type of drugs are used routinely in those in need of emergency artery-clearing angioplasty, where the current goal is to get the procedure started within 90 minutes of a patient turning up at the emergency room.
On the flip side, heart patients in need of more invasive coronary artery bypass procedures must wait until the anti-clotting effect of these drugs wears off in order to reduce the risk of catastrophic bleeding during surgery.
It typically takes about five days after the last dose of Plavix for clotting activity to return to normal enough levels to safely perform bypass surgery. Brilinta patients reached a comparable level three days after stopping the medicine, the study found.
From the PR it looks like the European trial didn't hit its primary endpoint rather a trend was seen: "A numerical increase in the number of SSEs compared to placebo supports the efficacy of flibanserin in pre-menopausal women suffering with HSDD." Also "about 14% and 16% of women on flibanserin 100mg and 8% and 5% of women on placebo discontinuing treatment due to AEs in the respective trials" (American and European). Seems high.
Here's another phosphate binder that wasn't good enough:
Genzyme negative news continues; stops drug trial
http://www.reuters.com/article/marketsNews/idUKBNG110820091118?rpc=44
* Genzyme stops trial of kidney disease drug
* Drug did not work better than company's existing product
* Shares fall 1.5 percent early trading
By Toni Clarke
BOSTON, Nov 18 (Reuters) - U.S. biotechnology company Genzyme Corp (GENZ.O: Quote, Profile, Research, Stock Buzz) reported more bad news on Wednesday, announcing it is dropping development of its experimental kidney disease drug after it proved no more effective than the company's existing drug Renvela.
The news comes as the company is struggling to resolve a series of manufacturing problems that have led to a shortage of its biggest-selling drug, Cerezyme, a treatment for Gaucher disease, a rare genetic disorder that can cause life-threatening organ damage.
Genzyme's shares fell 1.5 percent to $49.57 in early trading on Nasdaq.
Cambridge, Massachusetts-based Genzyme said it had hoped to develop a drug that was more potent than Renvela, itself a successor to the company's kidney disease drug Renagel. The active ingredient in the drugs is known as sevelamer.
Renvela treats hyperphosphatemia, or excess phosphate in the blood, a risk factor for cardiovascular disease in patients with chronic kidney disease.
"This is a very significant negative in our view," said Christopher Raymond, an analyst at Robert W. Baird, in a research note. "With Renagel/Renvela patent expiry in 2014, this program was seen as the primary vehicle to extend Genzyme's $850 million renal franchise."
Genzyme had been studying its new drug, an advanced phosphate binder, in 349 patients. The trial was in mid-to-late stage development.
"Without line extension for the Renagel-Renvela franchise, we estimate nearly $1 billion in sales is at risk for Genzyme looking to 2014," said Geoffrey Meacham, an analyst at J.P. Morgan, in a research report. "We view the franchise as vulnerable to generic sevelamer competition, which we assume will dominate the phosphate binder market in 2014."
Sad news. And I agree that the company is a victim of the complex nature of genetic diseases.
NGSX- the patch was approved by the FDA for the management of neuropathic pain due to postherpetic neuralgia.
http://finance.yahoo.com/news/NeurogesX-shares-rise-apf-3040400066.html?x=0&.v=3
An analysis of a new slice of data from the PLATO trial :
AstraZeneca drug tops Plavix in sickest patients
http://www.reuters.com/article/marketsNews/idCNN1545865820091115?rpc=44
* Astra's Brilinta tops Plavix in heart attack patients
* No increased major bleeding risk seen with Brilinta
* 18 pct reduction in all cause death seen with Brilinta
* Data from sickest 40 pct from larger PLATO trial (Add further researcher comment)
By Bill Berkrot and Ransdell Pierson
ORLANDO, Fla., Nov 15 (Reuters) - Heart attack patients in need of emergency procedures were less likely to suffer further serious cardiovascular events, including death, when given AstraZeneca's experimental Brilinta blood clot preventer than those who used Plavix, according to a study presented on Sunday.
Importantly, the Brilinta patients also were found to be at no greater risk for major bleeding than those taking Plavix -- an encouraging sign for such drugs that work by preventing blood cells called platelets from clumping together.
The lack of increased bleeding risk seen with AstraZeneca's (AZN.L: Quote, Profile, Research, Stock Buzz) new medicine could provide comfort that safety was not compromised in order to obtain its greater ability to prevent cardiovascular death, heart attack and stroke for up to a year.
The findings are an important new slice of data from a more than 18,000-patient comparative international trial called PLATO unveiled earlier this year in which Brilinta also proved superior to Plavix, one of the world's most widely used medicines sold by Bristol-Myers Squibb (BMY.N: Quote, Profile, Research, Stock Buzz) and Sanofi-Aventis (SASY.PA: Quote, Profile, Research, Stock Buzz) with annual sales of some $9 billion.
Analysts see Brilinta as a potential multibillion-dollar a year seller for AstraZeneca, which plans to file an application seeking U.S. approval later this year.
For the latest data, researchers focused on the 8,430 sickest patients in the PLATO trial -- those in the midst of so called ST-elevation heart attacks with total obstruction of at least one coronary artery who were in need of emergency angioplasty and stents to restore blood flow and save heart muscle.
"The results are very clear and actually very consistent with the overall trial results of the larger PLATO trial," preventing cardiovascular events while not increasing the major bleeding risk, said Dr. Philippe Gabriel Steg, lead investigator of the study that was presented at the American Heart Association scientific meeting in Orlando.
Steg said Brilinta, known chemically as ticagrelor, works much more quickly than Plavix, which could be an advantage in these patients in whom time to performing an artery clearing procedure is crucial.
"Clopidogrel's drawbacks include slower onset of effectiveness, which is not suited to the need for rapid effect in STEMI (ST-elevation heart attacks)," Steg said, using the chemical name for Plavix.
DEATH REDUCTION
According to the latest findings, 9.3 percent of patients receiving Brilinta suffered cardiovascular death, heart attack or stroke for up to a year, compared with 11 percent in the Plavix group, a statistically significant difference, researchers said.
There was an 18 percent relative reduction in death from any cause at one year in the Brilinta group, they said.
"This sets apart this drug and this study from all other oral agents studied so far," Steg said.
"In previous trials, other oral agents prevented cardiovascular events, but did not significantly reduce mortality," added Steg, who said the Astra drug could become "a standard of care" for managing very high risk patients undergoing angioplasty procedures.
He said the survival benefit suggests Brilinta may be protecting patients through mechanisms that are not yet known.
For these sickest heart patients in the study, the benefits seen with Brilinta increased over time, researchers said.
Another advantage demonstrated by Brilinta that could help once it begins competing with one of the world's top-selling medicines is how quickly its effects wear off.
Researchers said once the medicines are stopped, normal platelet clotting ability returns in fewer days than with the Astra drug, which could provide a real clinical difference in patients in need of more serious invasive procedures in which bleeding is a serious risk.
However, there are a couple of issues potentially standing in Brilinta's path to swift approval.
As seen in previous Brilinta studies, there was a higher incidence of breathlessness -- 12.9 percent versus 8.3 percent with Plavix -- that could be a signal of unintended impact on lung function. Steg said that side effect was mild and went away after a few days after the start of treatment.
There also was an as-yet-unexplained lack of benefit over Plavix seen in North American patients, who accounted for about 9 percent of total PLATO subjects but who would represent the most important market for the drug's future success.
There has been speculation that higher doses of aspirin being taken by U.S. patients in the study could account for the disparity, or that it was merely a statistical fluke.
But it is likely something the U.S. Food and Drug Administration will look at very carefully before making any approval decisions.
Vivitrol met the main goal of a phase III study in treatment of opioid dependence but I doubt this will make a big difference.
http://www.reuters.com/article/marketsNews/idCNBNG32982320091116?rpc=44
Complete response letter for Lumizyme (and another delay):
http://www.reuters.com/article/marketsNews/idCNBNG39487120091116?rpc=44
Statistics - The ARBITER 6–HALTS study
From the paper (http://content.nejm.org/cgi/content/full/NEJMoa0907569):
In a post hoc analysis, we explored the bivariate relationships between changes in LDL cholesterol levels and mean carotid intima–media thickness. There was a significant inverse relationship between the changes in LDL cholesterol level and the carotid intima–media thickness in the ezetimibe group (R=–0.31, P<0.001), such that a paradoxical increase in the carotid intima–media thickness was seen in patients with greater reductions in LDL cholesterol. Such a relationship was not observed in the niacin group (R=–0.01, P=0.92) (Fig. 4 in the Supplementary Appendix).
Results of ARBITER 6–HALTS Study
This trial doesn't quite put the nail in the coffin for ezetimibe
Re: Sex Really Is All in Her Head
A reminder of the debate about - from whence comes women sex drive? Note that female sexual dysfunction (FSD) encompasses a group of disorders, among these is hypoactive sexual desire disorder (HSDD), a decreased sexual desire independent from a medication or illness. The most telling sentence is this:
"By promoting the belief that “normal” women have explosive sex all the time, BigPharma helped launch the disease." - that idea is born of marketing and media. And the “horny goat weed extract” from #msg-26421440 is also mentioned...
http://www.inthesetimes.com/article/5016/
WHO guidelines presage US biosimilars legislation?
By John Hodgson Cambridge, UK. Nature biotechnology vol. 27 number 11 november 2009
As Nature Biotechnology went to press, the World Health Organization (WHO) in Geneva was finalizing a new set of guidelines for Similar Biotherapeutic Products. The WHO expects these draft guidelines, prepared by the Expert Committee on Biological Standardization, to be circulated to national regulators, manufacturers and other interested parties during 2010 and 2011. The guidelines, to which Keith Webber, deputy director of the Office of Pharmaceutical Science at the US Food and Drug Administration’s (FDA’s) Center for Drug Evaluation and Research contributed as a technical expert, come as the US prepares to draw up a long-awaited biogenerics pathway. But in the US, the debate over market exclusivity is threatening to divert the biosimilars discussion down an unproductive cul-de-sac, despite the introduction of bills for biosimilars legislation in the Senate (Senate HELP Health Care Reform bill) and the House of Representatives (HR 1548) during the summer.
When the US Congress enacted the US Drug Price Competition and Patent Term Restoration (Hatch-Waxman) Act 25 years ago, opening the way for the FDA to approve generic drugs, biologics were not included. Bill Haddad, chairman and CEO of Biogenerics in Brewster, New York, who was instrumental in initiating and negotiating the Hatch-Waxman Act takes that omission personally. “I made a big mistake 25 years ago,” he says, “and it’s time to make amends.” He is working with generics industry lobby groups such as the Generic Pharmaceutical Association in Arlington, Virginia, to accelerate the passage of US legislation on biosimilars. “The stakes are high,” says Haddad. “There are 25–30 [biologic] drugs out there with what amounts to perpetual patents.” History demonstrates, he believes, just how profound an impact biosimilars legislation could have. “Thirty-five years ago, when we were first thinking about the legislation that became Hatch-Waxman, generic compounds had only 5% [by volume] of the US pharmaceuticals market: now they have 85%.”
The impact of a biogeneric pathway, however, is unlikely to be as dramatic. In the first place, experience in the EU indicates that biosimilaroriginator competition is not comparable with the direct substitution that occurs with smallmolecule generics. The European Medicines Evaluation Agency’s (EMEA’s; London) approval pathway in 2005 has not triggered a deluge of biosimilars swamping existing markets. Some 12 products have been approved so far (Table 1) encompassing only three product classes (human growth hormone, erythropoietin (EPO) and granulocyte colony stimulating factor). Applications for follow-on insulin and interferon products have been refused or subsequently withdrawn.
According to Suzette Kox, senior director of Scientific Affairs at the European Generic Medicines Association in Brussels, the impact of biosimilars in Europe has not been profound. “There may be an overall 20–30% decrease in interchangecosts but, because the originator companies also drop their prices, market share may not shift so dramatically,” she explains. The continuing fragmentation of the healthcare market in Europe makes it difficult to assess the overall market share changes accurately. However, Islah Ahmed, the global medical director of Hospira, located in Lake Forest, Illinois, has aggregated data for Germany, the biggest single national pharmaceutical market in Europe. The data show that two years after launch, biosimilar EPOs represent ~35% of unit sales of short-acting EPOs, whereas substitution rates for small-molecule generics can exceed 90% in the first year.
The second reason to think that a biosimilars pathway in the US will have a muted impact is that industry lobbies, such as Biotechnology Industry Organization in Washington, DC, and the Pharmaceutical Research and Manufacturers of America, also in DC, have been hard at work ‘protecting their members’ interests’. Several pieces of competing legislation came before Congress this year. Bills proposed by Senator Sherrod Brown (D-Ohio) and Representative Henry Waxman (D-CA), which gave the greatest encouragement to manufacturers of follow-on biologics by proposing a period of five or seven years respectively, have faded from view. In June, the US Federal Trade Commission argued for zero years’ market exclusivity based on the premise that competition between originator compounds and biosimilars was likely to resemble brand-to-brand competition rather than a generic substitution model (Nat. Biotechnol. 27, 677, 2009). The Obama Administration’s position is that seven years of market exclusivity for novel biologic products is sufficient, in line with the interest of biosimilar producers.
Since July, however, the impetus has shifted to two ‘pro-innovation’ bills that have progressed through Congress rapidly because they are tied into the heath reform package (HR 3200). The Senate Health, Education, Labor and Pensions Committee introduced the ‘Hatch Amendment’ and the House Energy and Commerce Committee added the ‘Eshoo Amendment’. Both propose to provide developers of pioneer products with 12 years’ market exclusivity, regardless of the patent status of the product, based on an economic model outlined by Henry Grabowski of the Fuqua School of Business at Duke University (Nat. Rev. Drug Discov. 7, 479–488, 2008).
Buoyed by such high-level support for biosimilar- friendly legislation, the public relations campaign is likely take a new and more aggressive twist. Colleagues of Bill Haddad recently undertook an ad hoc survey of drug bills at municipal, volunteer and not-for-profits hospitals— those hospitals which act as the safety net for the majority of American sick and unininsured. Haddad claims that the high prices for biologics affects those hospitals severely. “The 5% of patients treated with biologics account for 45% of the drug bills in those hospitals,” he says. “Every Congressional district has hospitals that are struggling because of the high cost of biologics and that makes for a lot of local media coverage.” The next phase in the campaign will involve a detailed cost-and-profit breakdown for current ‘innovator’ products.
Although the short-term political fireworks will establish the magnitude of the contribution that biosimilars can make in the US, the deliberations at WHO will likely shape the nature of the regulatory process that FDA ultimately implements. The WHO draft guidelines on similar biotherapeutic products (http://www.who.int/biologicals/publications/trs/areas/biological_therapeutics/BS2110Dft_guidelines_Final_HK_IK_29July_09.pdf) were closed for comments on October 9, 2009, and the document was being deliberated by the WHO Expert Committee on Biological Standards as Nature Biotechnology went to press.
The WHO document is a guideline and has no legal force on WHO member states. But the document has political significance because it is unlikely that it would contain proposals unacceptable to regulators in such countries as the United States and China. “Personally, we do not expect the USA to have a scientifically different approach to the EU or Japan,” says Kox. “There are some significant principles in the [WHO] Guidelines.” Jacques Mascaro, senior vice president, global regulatory affairs, pharmacovigilance and quality from Dublin-based Elan, was involved in establishing the EMEA biosimilar guidelines in the EU and has reviewed the WHO guidance documents as an innovator industry representative. He agrees that the WHO guidelines are “an important step” that provides “an agenda to move things along.”
Mascaro was keen not to appear to be telling the FDA what to do. He nevertheless raised three key issues of interest. “Firstly, will the FDA take a case-by-case approach? Secondly, will it integrate the data and experience that already exists from assessments in the EU and elsewhere? And, thirdly, what will be the position with respect to the interchangeability of products?”
The WHO draft guidance provides clear direction to the first and third questions. It states that the basis for licensing a biosimilar—similar biotherapeutic product (SBP), in WHO parlance— depends on “its demonstrated similarity to a suitable reference biotherapeutic product in quality, nonclinical and clinical parameters.” So, yes, there should be a case-by-case approach. Furthermore, the WHO guidance indicates that “automatic substitution of SBP is not recommended” and that decisions on interchangecosts ability of reference and similar biotherapeutics “should be made by physicians.” Therefore, no assumed substitutability of similar products.
As to the second question, the WHO guidance says very little about whether the data gathered and examined for the approval of a similar biotherapeutic in one territory could or should be used in another. The EGA is pushing national regulators to accept data globally. “If you have a highly similar compound and the same reference compound, then we think the information should be transferable,” says Kox. “Same reference product—same data package.” Jacques Mascaro, too, thinks that the FDA is keen to learn from the European regulators, perhaps by keeping a watching brief rather than by welcoming European data submissions wholesale. “The EU is relatively advanced with biosimilars, but the FDA may want to see how the products perform post-approval before implementing its own system.”
Bill Haddad, however, hopes that the FDA will move soon. “We could have regulations in place in 2010 and the first biosimilar approvals in the USA in 2011,” he says. He believes that putting the system in place earlier rather than later would make a significant difference to President Barack Obama’s healthcare plans by saving an estimated $100–200 billion in drug costs. “The savings over the 10 years of the plan would be enough so that he [Obama] doesn’t have to spend one penny over budget on Universal Healthcare.”
Desire Drug May Prove Sex Really Is All in Her Head
http://www.bloomberg.com/apps/news?pid=20601202&sid=a1dWw6lHCAJQ#
By Naomi Kresge
Nov. 13 (Bloomberg) -- Boehringer Ingelheim GmbH is banking on sex really being all in women’s heads.
The German drugmaker is putting the finishing touches on a pill designed to reawaken desire by blunting female inhibitions. Unlike Viagra, which targets the mechanics of sex by boosting blood flow to the penis, this drug works on the brain.
The desire drug, the focus of a meeting on sexual disorders in Lyon next week, has the potential to revolutionize sexual medicine much as Pfizer Inc.’s blue pill did a decade ago. That could put family-owned Boehringer at the center of a debate about whether the medicine is a chemical shortcut around a complex dysfunction involving body and mind -- or whether disinterest in sex is a legitimate medical condition.
“This drug has the potential to finally open the door to acceptance of the idea that decreased desire can be something that involves a dysfunctional way the brain works, and not only a bad partner,” said Jim Pfaus, a neurologist at Concordia University in Montreal, who conducted early tests of the drug in rats. “Of course it’s in your head.”
The U.S. market for medicines to rekindle female libido could be bigger than the $2 billion a year in U.S. sales for erectile dysfunction treatments because more women report sexual problems, BioSante Pharmaceuticals Inc. Chief Executive Officer Stephen Simes estimated last year.
Showing It Works
Boehringer, based in the German town of Ingelheim on the Rhine’s west bank, was searching for a depression treatment in the 1990s when it stumbled on the compound, called flibanserin. By 2002, Boehringer found the drug wasn’t lifting patients’ mood. The company says researchers were startled when test subjects rated one measure of well-being, sexual appetite, consistently higher than the others.
After what Pfaus described as an initial period of hesitation about developing a sex pill, Boehringer decided to move forward. The company needs new drugs because it faces the loss of 1 billion euros ($1.5 billion) in annual revenue when two older medicines, Mirapex for Parkinson’s disease and Flomax to treat enlarged prostate, lose patent protection next year.
The world’s largest closely held pharmaceutical company has been studying flibanserin for more than a decade and it has yet to publish clinical test results showing the drug is effective. The company will lift its veil of secrecy on Monday at the European Society for Sexual Medicine conference with data from trials of more than 5,000 European and U.S. women.
Women’s Distress
The main criterion for the clinical trials, which the company named after flowers, was how many “satisfying sexual events” women said they had experienced after starting treatment. If the results are good, the so-called Bouquet studies, dubbed Violet, Daisy, Dahlia and Orchid, could form the basis for applications to U.S. and European regulators.
The German company is taking a page from Pfizer’s book. The U.S. drugmaker broadened the appeal of Viagra in 1998 by steering clear of the word “impotence” and saying the blue pill addressed a disease called erectile dysfunction. Boehringer is avoiding potentially offensive words such as frigidity and refers to the problem its pill cures by its clinical name, hypoactive sexual desire disorder, or HSDD.
“An increasing body of evidence shows that hypoactive sexual desire disorder causes substantial emotional distress,” said Heike Specht, a spokesman for the company. The drugmaker “has conducted late-stage clinical trials in over 5,000 women from which we hope will result the first available pharmaceutical treatment.”
A Boehringer survey of 31,000 U.S. women aged 18 and above found that one in 10 expressed distress because of diminished sex drive.
Ideological Battle
A sluggish libido is “a real problem,” and early clinical results so far suggest Boehringer’s drug can help, according to Stephen Stahl, a psychopharmacologist and chairman of the Neuroscience Education Institute in Carlsbad, California. Stahl, who has been a consultant for Boehringer, sees a growing role for drugs in treating sexual disorders.
Not everyone agrees there is a disorder to begin with.
In 2003, a year after Boehringer started the Bouquet clinical trials, an article written by Ray Moynihan in the British Medical Journal called female sexual dysfunction “the freshest, clearest example we have” of a disease created by pharmaceutical companies to make healthy people think they need medicine.
“This is for some an ideological battle,” said psychiatrist Michael Berner of the Freiburg University Clinic, who had patients in Boehringer’s studies. “One view is the multi-dimensional view you get from people like me. And then you have these people that say you should work only on relationship issues and that medication cannot have a place.”
‘Like Dancing’
Researchers don’t know why some women’s libido falters, said Pfaus, who has tested compounds in rats for Pfizer, Boehringer and Palatin Technologies Inc. by gauging whether they spur female rats to solicit sex from males.
“An erection is obvious, it’s easy,” Pfaus said. “But desire -- how do you get at that?”
The explanation may be partly evolutionary, according to Berner, who says male primates are driven by a need to spread their semen, while for females it’s important to be able to care for and rear the offspring.
Some researchers believe the social components of intercourse mean that sexual problems can’t be addressed in the same way as heart failure or cancer.
Sex is a “historical and cultural phenomenon,” said Leonore Tiefer, a psychiatry professor at New York University. There’s no baseline of normalcy by which to define a disorder, she contends.
“It’s like dancing, or music, or piano-playing,” Tiefer said. “You do it with the body, but the part the body plays isn’t the largest part.”
Over the Wall
Flibanserin works on the brain by putting “two feet on the brakes” to block the release of a chemical called serotonin, which regulates mood, appetite, sleep and memory, Pfaus said. In time, the process should trigger the production of dopamine, a chemical that, among other jobs, helps stimulate desire.
The drug differs from testosterone, a hormone that’s also been tested to reawaken women’s desire. Berner, interviewed at his study in Freiburg, sketched the picture of a wall to explain how flibanserin works.
“You’re standing here, sad, inhibited,” he said, drawing a stick figure next to the wall on a scrap of paper. “Testosterone would give you a little bit more excitement, so you’d climb over. Flibanserin would take away one of the stones.”
Once a Day
The compound takes three to six weeks to kick in. The pill has to be taken daily, and some women taking part in the clinical trials reported feeling tired, Berner said.
Boehringer recruited women for clinical studies using print advertisements. Berner said his patients were largely professionals in their early 30s to mid-40s, and most chose to continue in the trial in a subsequent phase that ensured they would get the real drug instead of a placebo. Boehringer is recruiting older women for a follow-up study.
Women can be diagnosed with hypoactive sexual desire disorder if they feel concerned, bothered or frustrated by a lack of desire -- or if it’s hurting their relationships.
The company used personal digital assistants to check whether the pill was working. Participants were beeped once a day and asked to rate their level of desire and say whether they had been sexually active and whether it was enjoyable.
Potential Rivals
If flibanserin makes it to market, it will be the first success after a series of failures from drugmakers including Procter & Gamble Co. and Pfizer. The New York-based maker of Viagra abandoned efforts to adapt its pill for women in 2004 and closed sex-health research at the end of last year.
The only female sexual dysfunction therapy approved in the U.S. is Eros-CTD, from NuGyn, Inc., a suction pump that fits over the clitoris much like the erection pumps that predated Viagra. Intrinsa, a testosterone patch from Noven Pharmaceuticals Inc. licensed by Procter & Gamble, is sold in Europe for women whose uteruses have been removed. A U.S. version was put on hold in 2004 on concern about whether it is safe for long-term use.
Still in clinical trials are a new version of the P&G patch; LibiGel, a testosterone gel from BioSante; and bremelanotide, an injected therapy from Palatin Technologies.
Researchers around the world will be watching Boehringer’s results in Lyon, according to Pfaus. “There are probably a lot of companies holding their breath,” he said.
GENZ just can't get enough manufacturing issues. It has a November 14 PDUFA date for Lumizyme 2000L facility, which its guidance has been for an approval but will probably be delayed.
BMY has a $1.75B payment coming from a debt refinancing by Mead Johnson Nutrition.
Since Gamunex is, as you noted, Talecris's biggest product, and it is facing a future competition from Baxter's IGIV, I was thinking, maybe this puts extra pressure on Talecris to move on with its inhaled AAT program. Talecris like Kamada also got an orphan drug designation and if approved first, they may block Kamada's inhaled AAT.
Any mention of the inhaled AAT program? T.i.a
[After each report, Merck said doctors shouldn’t change treatment based on the results and urged them to wait for data from a larger trial to be completed in 2012.
FDA makes a judgment and doesn't just follow the rote statutory definitions - which are clearly not perfectly aligned with chemical reality.
however, Copaxone isn’t a biologic
Teva won a ruling and got an FDA approval so it can begin selling a generic version of Takeda's Prevacid.
Nebido could be approved around its PDUFA date - Dec. 2nd with REMS and probably a black-box.
You probably refer to Actemra (Roche/Chugai), which is approved in EU and Japan and indeed is associated with death and severe side effects reported in the post marketing study in Japan. However, that doesn't kill the whole class yet because not all the anti IL-6 antibodies are the same for example: JNJ/CNTO human monoclonal antibody to IL-6, which binds the cytokine and not the receptor, like Actemra.
BMY signs development deal for a Phase II humanized monoclonal antibody targeting IL-6 in Ra:
Bristol-Myers signs development deal with Alder
http://finance.yahoo.com/news/BristolMyers-signs-apf-3430744848.html?x=0&.v=2
Bristol-Myers Squibb signs development deal for rheumatoid arthritis drug with Alder Biopharma
NEW YORK (AP) -- Bristol-Myers Squibb Co. and Alder Biopharmaceuticals Inc. said Tuesday they signed a collaboration deal potentially worth $1 billion, with a key focus on a rheumatoid arthritis treatment.
Bristol-Myers will pay Alder $85 million upfront for ALD518, which is now past midstage development for rheumatoid arthritis, an inflammatory condition that can cause joint damage. The agreement also includes the potential for development-based and regulatory-based milestone payments of up to $764 million and sales-based milestones that could be more than $200 million.
Alder will also receive sales royalties. Meanwhile, Alder gives Bristol-Myers exclusive worldwide rights to develop and sell ALD518 for all potential indications, excluding cancer.
Bristol-Myers already sells the drug Orencia as a rheumatoid arthritis treatment. Sales rose 36 percent to $162 million during the third quarter.
Alder, based in Bothell, Wash., has an option to require New York-based Bristol-Myers Squibb to make an equity investment of up to $20 million in Alder during an initial public offering.
And how is this relevant to 'Israel-Medical-Healthcare' board?
Most analysts and scientists think the trial was halted because Niaspan outperformed Zetia
SGP was hoping for its IDEAL study (data were reported in early 2008), to demonstrate Pegintron superiority over Pegasys but that didn't happen. Inasmuch as Pegasys' superiority was quite established by the time SCH 900518 clinical program has progressed, you have a point.
Chinese co to fund D-Pharm Phase III trial
http://www.globes.co.il/serveen/globes/DocView.asp?did=1000512036&fid=1725
D-Pharm could receive milestone payments of up to $25.5 million.
Gali Weinreb 8 Nov 09 17:10
D-Pharm Ltd. (TASE: DPRM), which is developing a stroke treatment drug, has signed a partial licensing agreement for its product with Chinese company Wanbang Biopharmaceuticals, a subsidiary of Fosun International Ltd. (HKSE: 656), one of China's largest pharmaceutical companies.
Under the terms of the agreement, Wanbang will receive an exclusive license for development, conducting trials, manufacturing pharmaceuticals from active agents, registration, sales and distribution in China of DP-b99, D-Pharm's lead product for treating strokes.
In return Wanbang will finance D-Pharm's Phase III trial in China and in addition will pay milestone payments of up to $25.5 million with the first payment due in the coming days. If and when the product is marketed in China, D-Pharm will be eligible for significant royalty payments on sales of the product.
The Phase III trial, which will include 450 patients, will be supervised by the US Food and Drug Administration (FDA). D-Pharm will be able to use the results as part of its multi-center FDA trial - the final trial required by the FDA before marketing approval is considered.
D-Pharm's main shareholders are Clal Biotechnology Industries Ltd. (TASE: CBI) (46.5%), Care Capital (8.4%), Israel Health Care Ventures (7.45%), and Pitango (7.45%).
One item in the complaint is that ZGEN reps have been scaring customers telling them that re exposure to KG's Thrombin-JMI causes deaths. "The lawsuit accuses ZymoGenetics of unfair competition, false advertising, trademark infringement and related claims, ZymoGenetics said."
Meanwhile, restraining orders were lifted
http://seattle.bizjournals.com/seattle/stories/2009/11/02/daily49.html?ana=yfcpc
this filing may signal that reco is starting to take a more meaningful share of the market.
The more consequential events for Teva are no doubt linked to Copaxone. In addition to the ending of the 25% royalty payments to Sanofi after Apr 2010 that you've mentioned, any direct event like the M356 litigation with MNTA (Markman hearings is due in Dec), or indirect one such as FDA action on MNTA's M-Enoxaparin, would be consequential. An acquisition should be consequential as it would diversify away from Copaxone.
Scientific Meeting Calendar
NOTE: ANYONE MAY UPDATE THIS FILE
Edits: Added entries for Gastro 2009, ASCB, SABCS
OCTOBER 2009
American College of Chest Physicians - CHEST
October 31 - November 5, 2009
San Diego, California
http://www.chestnet.org/CHEST/program/about09.php
NOVEMBER 2009
American College of Allergy, Asthma & Immunology - ACAAI
November 5-11, 2009
Miami Beach, FL
http://www.acaai.org/Member/Annual_Meeting/Annual+Meeting.htm
American Heart Association - AHA
November 14-18, 2009
Orlando, Fl
http://scientificsessions.americanheart.org/portal/scientificsessions/ss/seeyounextyear2009
Gastro 2009
November 21-25, 2009
London, UK
http://www.gastro2009.org/
DECEMBER 2009
American Epilepsy Society - AES
December 4-8, 2009
Boston, MA
www.aesnet.org
American Society of Hematology - ASH
December 5-8, 2009
New Orleans, LA
http://www.hematology.org/meetings/2009/index.cfm
International Respiratory Congresses - AARC Convention
Dec. 5–8, 2009
San Antonio, Texas
http://www.aarc.org/education/meetings/#future_congress
American Society of Cell Biology - ASCB
December 5-9, 2009
San Diego, CA
http://www.ascb.org/meetings/
American College of Neuropsychopharmacology - ACNP
Dec 6-10, 2009
Hollywood, Florida
www.acnp.org
San Antonio Breast Cancer Symposium - SABCS
December 9-13, 2009
San Antonio, Texas
http://www.sabcs.org/Overview/
--
Procedure for Updating Calendar
When adding or modifying entries, please follow these steps:
1. Copy the complete text from the old calendar.
2. Make your additions or modifications, inserting any new items in chronological order.
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ITMN/pirfenidone
Drug performed the same in both trials
VRTX
Still, it seems odd that Graves would abandon one of the highest-profile jobs in the biotech industry without something else lined up, and it’s conceivable that there are skeletons in the Telaprevir closet that influenced Graves’ decision.
We won’t know for sure until some time in 2011, when the FDA convenes an advisory panel for Telaprevir.
CRME
On vernakalant(i.v): There's a head-to-head phase III trial in Europe of vernakalant vs amiodarone for acute AF conversion. (http://clinicaltrials.gov/ct2/show/NCT00668759?term=AVRO&rank=1)
If vernakalant shows superior efficacy with adequate safety (I think it will), it will become the drug of choice for conversion of AF, and the European label might include HF patients.
Oral vernakalant likely will be safer but less effective than amiodarone, but will be interesting how it will compare to Multaq.
Dr. Aviezer at Oppenheimer conference repeated the ability to treat about 1,000 patients and 1,500 more in 2010. On partnering he said it is very likely to be signed before approval.
Despite the potential as a small molecule to cross the blood-brain barrier, it hasn't shown improvement in neurologic symptoms in patients with type 3 GD.