Sanofi

Covid-19: Sanofi and GSK to seek regulatory authorisation for protein based vaccine

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Sanofi and GlaxoSmithKline’s covid-19 vaccine has 57.9% (95% confidence interval 26.5% to 76.7%) efficacy against any symptomatic disease, the companies have reported.

In a phase 3 trial in which more than 10 000 adults were randomised to receive two doses of the vaccine or placebo, 21 days apart, researchers found it to have 100% efficacy against severe disease and hospital admission (0 v 10 cases in placebo group after one dose, 0 v 4 cases after two doses) and 75% efficacy against moderate or severe disease (3 v 11 cases).

Early data has also indicated 77% efficacy against any symptomatic disease associated with the delta variant, French drug company Sanofi has said. So far, details of the trial have been released only through press release, although the companies said full study results will be published later this year.

Thomas Triomphe, executive vice president of Sanofi vaccines, said, “No other global phase 3 efficacy study has been undertaken during this period with so many variants of concern, including omicron, and these efficacy data are similar to the recent clinical data from authorised vaccines.”

The protein based vaccine can be kept at refrigerator temperatures, making it easier to store and transport than some of the other vaccines, such as the mRNA vaccines (Pfizer-BioNTech and Moderna), which require shipping and long term storage at −20°C or lower.

Melanie Saville, executive director of vaccine research and development at the Coalition for Epidemic Preparedness Innovations (CEPI), told The BMJ, “Protein based vaccines like GSK-Sanofi’s updated candidate offer a new era in the global covid-19 vaccination effort … Protein based candidates may generate different immunological profiles from other covid-19 vaccine approaches, which may have a favourable profile in certain demographics, like the elderly or young populations. These vaccines are generally well tolerated.”

She added that as the vaccine is stable at refrigerator temperatures, “it doesn’t require the complex cold chains that have limited the use of other covid-19 vaccines in remote or low resource settings” and should reduce vaccine waste globally.

In a separate trial, the vaccine was tested as a booster dose for people who had previously had two doses of an mRNA or adenovirus vaccine (such as Oxford-AstraZeneca). The booster dose was found to increase neutralising antibodies 18-fold to 30-fold across different vaccine platforms and age groups.

Across both studies, the vaccine was well tolerated in younger and older adults with no safety concerns, the press release said.

The companies are now in discussions with regulatory authorities, including the US Food and Drug Administration and European Medicines Agency, and plan to submit for regulatory authorisation shortly.

GSK vaccines president, Roger Connor, said, “The evolving epidemiology of covid-19 demonstrates the need for a variety of vaccines. Our adjuvanted protein based vaccine candidate uses a well established approach that has been applied widely to prevent infection with other viruses, including pandemic flu. We are confident that this vaccine can have an important role as we continue to address this pandemic and prepare for the post-pandemic period.”

WHO’s Strategic Advisory Group of Experts (SAGE) recommends Sanofi’s dengue vaccine to curb spread of disease.

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WHO’s Strategic Advisory Group of Experts (SAGE) has recommended the use of Sanofi’s dengue vaccine- Dengvaxia  to control the spread of the life threatening mosquitoe borne disease. Dengvaxia has already been already approved for four countries including Brazil and Mexico.

In a statement Sanofi reps stated that, ” The SAGE advises that countries with high dengue transmission consider introduction of the dengue vaccine as part of an integrated disease prevention strategy including vector control to effectively lower their dengue disease burden.”

Vaccine’s Effectiveness

Dengvaxia vaccine’s anticipated impact on dengue fever disease burden is expected to stem from the vaccine’s proven ability to prevent 8 out of 10 dengue hospitalizations and up to 93 per cent of severe dengue cases–including dengue hemorrhagic fever–in study participants 9 years and older, as demonstrated during 25 months of follow-up of phase III efficacy studies.

WHO’s Objectives

The WHO has set objectives to reduce dengue morbidity by 25 percent and mortality by 50 percent by 2020. The recommendations from the SAGE are based on the technical review of clinical data from 25 clinical studies conducted in 15 different endemic and non-endemic countries around the world, including more than 40,000 study participants.

Major Bleed Risk Falls with Bivalirudin vs Heparin en Route to PCI for STEMI: EUROMAX.

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The 30-day risk of death or major bleeding fell significantly in ST-elevation MI (STEMI) patients treated with bivalirudin (Angiomax, the Medicines Company) compared with heparin-based management, both initiated prior to arrival at a hospital for primary PCI, in a large randomized but open-label study[1].

The bivalirudin benefit for that composite end point in the European Ambulance Acute Coronary Syndrome Angiography(EUROMAX) trial was driven by a significant drop in major bleeding, the definition of which excluded bleeding related to CABG surgery.

The heparin-based strategy consisted of either unfractionated heparin (UFH) or the low-molecular-weight heparin enoxaparin(Lovenox, Sanofi). Both groups could receive a GP IIb/IIIa inhibitor provisionally.

EUROMAX was published today in the New England Journal of Medicine with lead author Dr Philippe Gabriel Steg (Hôpital Bichat, Paris, France) to coincide with his presentation of the trial here at TCT 2013 .

http://img.medscape.com/news/2013/ih_131030_Steg_Philippe_Gabriel_TCT2013_120x156.jpg

Dr Philippe Gabriel Steg

Bivalirudin’s 40% primary-end-point relative risk reduction included a >50% drop in risk for non-CABG major bleeding. On the other hand, the relative risk of stent thrombosis with bivalirudin was nearly threefold what was seen in the heparin group, although absolute rates were very low.

At a media briefing on the trial, Steg said the excess stent thromboses with bivalirudin were driven by events in the acute phase, within 24 hours of PCI. And, he observed, they didn’t translate into more reinfarctions or ischemia-driven revascularization.

Still, “acute stent thrombosis . . . while rarely fatal and not outweighing the advantages of bivalirudin, is the only troubling issue with bivalirudin in STEMI, and we do need strategies to reduce this complication,” according to Dr Gregg W Stone (New York-Presbyterian Hospital/Columbia University Medical Center New York, NY), the assigned discussant following Steg’s formal presentation of EUROMAX.

Shades of HORIZONS AMI

The trial’s findings are reminiscent of the HORIZONS AMI trial 30-day outcomes reported about six years ago and covered then by heartwire . That trial, Steg et al observe, preceded some important changes in STEMI management and PCI technique that likely affected bleeding risk, changes that were a part of EUROMAX. These included the expansion of radial-artery PCI access, newer antiplatelet agents, reduced GP-IIb/IIIa-inhibitor use, and progressively earlier initiation of IV anticoagulants.

In the >3600-patient HORIZONS AMI, anticoagulation wasn’t started early during transport. But both it and EUROMAX with its nearly 2200 patients saw a decreased bleeding risk and increased stent-thrombosis risk with bivalirudin compared with heparin. But in contrast to EUROMAX, the earlier trial also showed a reduced risk of cardiac death in bivalirudin patients.

The two studies taken together have more to say than either alone. “I think the results of EUROMAX will heavily impact clinical use of bivalirudin in Europe,” Steg said to heartwire . “The results are very consistent wih HORIZONS AMI, even to the point of the stent-thrombosis signal” and are “reassuring enough to embrace [bivalirudin] in the prehospital setting.” That is, he added, “If you want to. [The EUROMAX results] are not mind-blowing because we don’t see a mortality reduction. But they suggest that the benefits seen in HORIZONS AMI can be extended to the contemporary prehospital setting. “

At the media briefing, Dr Bernard Gersh (Mayo Clinic, Rochester, MN), who wasn’t involved in the trial, said, “It’s not that often that you see trials that really will change clinical practice, and I think this will.”

The Role of Prehospital Diagnosis and Treatment

Gersh also said, “I’ve never seen really anything that suggests that prehospital administration [of anticoagulants] and [STEMI] diagnosis is not beneficial.”

But whether they are achievable in the field varies by country, even within Europe. Interviewed, Steg pointed out that at most participating centers, there were no physicians in the ambulances. It does take some expertise to interpret the ECGs, unless the tracings can be transmitted to a center for remote reading. But, he said, “It’s been shown in other trials if you have good trained paramedics, they do just as well if not better than physicians.”

Also speaking at the briefing as a EUROMAX observer, Dr Philippe Généreux (NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, NY) said prehospital STEMI diagnosis and treatment initiation could make the most difference in countries like Canada, “where there aren’t cath labs on every corner” and it might take 45 to 60 minutes for an ambulance to reach a PCI center.

Prospects for prehospital management in the US seem more remote, observers agreed. Dr James B Hermiller, Jr (St Vincent Hospital/The Heart Center of Indiana, Indianapolis,) said at the briefing, “The barrier to this in the US is very great. It’s difficult just to  get ECGs in the field, let alone administer anticoagulants, but we need to get there because this is very important.”

The Open-Label Randomization

EUROMAX randomized patients at centers in nine European countries presenting within 12 hours of onset of symptoms from electrocardiographically defined STEMI, on an open-label basis, to the bivalirudin or heparin strategies. Treatment was initiated in the ambulance or at a non-PCI hospital with subsequent transport to a PCI center.

For the 1089 patients who received bivalirudin, the drug was started as a 0.75-mg/kg bolus followed by an infusion of 1.75 mg/kg/h continued for at least four hours after PCI. The 1109 control patients received UFH at either 100 IU/g or 60 IU/kg with a GP IIb/IIIa inhibitor or were allowed to have enoxaparin at 0.5 mg/kg. Adjuvant GP IIb/IIIa inhibitors were allowed at physicians’ discretion. All patients received aspirin plus a P2Y12 inhibitor.

Relative Risk (95% CI) for Outcomes, Bivalirudin vs Heparin Strategies for STEMI Initiated During Emergency Transport to Primary PCI

End points

RR (95% CI)

p

30-day death from any cause or non-CABG major bleedinga

0.60 (0.43–0.82)

0.001

30-day death from any cause, reinfarction, or non-CABG major bleeding

0.72 (0.54–0.96)

0.02

Non-CABG major bleeding

0.43 (0.28–0.66)

<0.001

Major bleeding (TIMI definition)

0.62 (0.32–1.20)

0.15

Severe or life-threatening bleeding (GUSTO definition)

0.61 (0.22–1.68)

0.33

Definite stent thrombosisb

2.89 (1.14–7.29)

0.02

a. Primary end point 
b. Academic Research Consortium criteria

No significant differences were seen at 30 days for the composite of death, reinfarction, ischemia-driven revascularization, or stroke, or for any stroke or ischemic stroke. A committee blinded to treatment assignment adjudicated bleeding episodes and clinical events.

As discussant, Stone pointed out that PCI via the radial artery, rather than the femoral artery, was done in only 6% of cases in HORIZONS AMI but in 47% of EUROMAX patients. Some predicted that the greater proportion of radial procedures would lead to a much lower major bleeding rate and make it hard for bivalirudin to show an effect. A EUROMAX subgroup analysis found, however, that the benefits of bivalirudin over the heparin-based strategy were consistent for different kinds of patients, including whether their PCI was by the radial or femoral routes.

“Therefore, bivalirudin is beneficial regardless of the access site, and this is because most bleeding in the STEMI and ACS setting is not access-site related,” he said. It’s the non–access-site bleeds to pose the greater threat to later outcomes. So, he said, “the advantages of bivalirudin are present in patients undergoing radial as well as femoral intervention, and radialists should pay attention to this.”

Stone said EUROMAX raises the question of whether using cangrelor (the Medicines Company) as part of the accompanying antiplatelet therapy might help prevent stent thrombosis with bivalirudin, and that’s being addressed in HORIZONS-AMI-2, which is starting soon.

Cancer Risk From Diabetes Drugs Unproven, Say AACE/ACE.

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There is insufficient evidence linking glucose-lowering medications with an increased risk for cancer, and clinicians can continue to “confidently” prescribe all such Food and Drug Administration (FDA)–approved agents for the management of hyperglycemia, the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) say in a joint consensus statement released yesterday.

“For most people with diabetes, the benefits of treatment should take precedence over concerns for potential low-grade cancer risk until more definitive evidence becomes available,” according to the AACE/ACE task force for diabetes and cancer.

However, the group also recommends that physicians should “exercise caution when choosing medications implicated in the etiology of cancer for patients with the specific organ-related risk.”

Recent concern has emerged regarding links between diabetes drugs and cancer. In particular, debate has surrounded both a possible link between incretin drugs and pancreatic cancer and between basal insulin glargine (Lantus, Sanofi) and cancer.

But, the AACE/ACA task force explains, evidence suggests that both diabetes itself and obesity may increase the risk for certain cancers, and thus far there are no large-scale randomized studies to definitively link any medication with an increased cancer risk.

The 19-page document reviews the current evidence related to cancer and obesity, endogenous insulin, and diabetes itself, as well as to the various antihypertensive medications.

The authors note that the time lag between exposure to any carcinogen and cancer in humans can be as long as 20 to 50 years. “This is an essential point to consider when weighing the totality of evidence linking disease-state relationships with cancer or the role that pharmacotherapy may play in cancer development.”

Cancer screening and counseling on lifestyle changes should be a part of regular preventive care in people with obesity and/or diabetes, the group advises. Conversely, people who develop “typical” obesity-related cancers, especially at a younger age, should be screened for metabolic abnormalities.

When a physician prescribes antihyperglycemic medications, “a comprehensive risk/benefit analysis must be performed to include assessment of baseline personal and familial risk of malignancies in specific organ systems.”

And in general, “the current totality of evidence should not change clinical practice, though clinicians should be alert to the potential risk and should monitor patients more closely.”

On the flip side, there has also been emerging evidence that metformin and possibly the thiazolidinediones (TZDs) could be associated with a lower risk for cancer, the task force says. “Nonetheless, it is premature to prescribe metformin and TZDs solely for these as-yet-unproven indications.”

Source: medscape.com

Zolpidem and Driving Impairment — Identifying Persons at Risk.

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Zolpidem (Ambien, Sanofi) is the most widely used prescription drug for insomnia and one of the most commonly used drugs in the United States. Treatment of insomnia, which has important effects on patients’ quality of life, may also have larger public health benefits. In its 2006 report, the Institute of Medicine (IOM) Committee on Sleep Medicine and Research concluded that sleep deprivation and sleep disorders represent an unaddressed public health problem that has substantial health consequences and leads to high health care costs.1 The IOM noted that one of every five serious injuries from driving accidents can be attributed to driver sleepiness. Numerous sleep drugs are available for treating insomnia and are also used to reduce next-day somnolence. But it is widely recognized that these drugs themselves can sometimes contribute to next-day somnolence, depending on such factors as drug dose, dosage form, and individual patient characteristics.

The treatment of insomnia may focus on two distinct problems: falling asleep and remaining asleep; drugs that treat insomnia may be directed at one or both of these problems. For patients whose main problem is falling asleep, shorter-acting drugs can be effective without conferring a risk of sedation the following morning. When the problem is staying asleep during the night (sleep maintenance), longer-acting drugs — drugs with longer half-lives or controlled-release formulations — are generally used. Some patients can also take a very small dose of a sleep drug (e.g., zolpidem is available at a dose of 1.75 to 3.5 mg) or a very short-acting drug (e.g., zaleplon) if they wake up in the middle of the night and have difficulty falling back asleep.

Zolpidem was initially approved, in 1992, in an immediate-release formulation (Ambien) for insomnia characterized by difficulty in falling asleep. At the time of its approval, there was concern regarding morning impairment, even after a 7-to-8-hour period of sleep, particularly with regard to activities requiring full alertness, such as driving a motor vehicle. There was also some recognition that people’s risk of impairment could vary, and the drug label advised that “the dose of Ambien should be individualized.” Although the recommended adult dose was 10 mg, the recommended dose for the elderly (who had higher levels of the drug in their blood the next morning) and for patients with hepatic impairment (who metabolized the drug more slowly) was 5 mg. Individual differences became more apparent as new dosage forms of zolpidem were developed to address sleep maintenance and middle-of-the-night waking.

In 2005, a modified-release formulation of zolpidem (Ambien CR, Sanofi) was approved for insomnia characterized by difficulty falling asleep, difficulty staying asleep, or both; it came in a 12.5-mg dose. In 2011, a sublingual, lower-dose tablet (Intermezzo, Purdue) was approved for difficulty falling back to sleep after a middle-of-the-night awakening. Intermezzo was labeled so as to provide doses of zolpidem that differed for men and women (3.5 mg for men and 1.75 mg for women), since new data revealed a difference between men and women in morning blood drug levels.

The review and approval of Intermezzo was particularly informative, because a study was conducted to assess the relationship between blood zolpidem levels and driving impairment. The study assessed patients 3 hours after taking the drug (the label instructs patients to take the product at least 4 hours before morning awakening) and revealed significant impairment in driving ability in patients whose blood concentration of zolpidem was above 50 ng per milliliter. Such impairment is thought to increase the risk of a motor vehicle accident.

Recognition of a threshold blood level that would lead to concern about driving allowed assessment of other dosage forms of zolpidem in order to determine what doses would pose a risk of morning driving impairment. In some patients — particularly women, who clear zolpidem more slowly than men — blood levels the morning after taking the recommended bedtime doses could be considerably higher than 50 ng per milliliter. Reanalysis of data from studies of immediate-release zolpidem products showed that 8 hours (i.e., a typical period of sleep) after taking 10 mg of an immediate-release zolpidem product, 15% of women and 3% of men still had blood zolpidem levels of 50 ng per milliliter or higher; when a modified-release higher-dose (12.5 mg) product was taken, the percentages were much higher — 33% of women and 25% of men. These findings, consistent with the sex difference observed with the sublingual low-dose product (Intermezzo), prompted the Food and Drug Administration (FDA) earlier this year to revise the dosing recommendations for the labels of zolpidem-containing products to lower doses, particularly for women.2,3

Manufacturers of zolpidem-containing products, such as Ambien, Ambien CR, Edluar, and Zolpimist, must now make dosage recommendations that differ for women and men, to decrease the likelihood that women will have blood levels of the drug after they wake up that will impair their driving ability. Accordingly, the recommended dose of zolpidem for women has been reduced from 10 mg to 5 mg for immediate-release products (Ambien, Edluar, and Zolpimist) and from 12.5 mg to 6.25 mg for modified-release products (e.g., Ambien CR). Although labeling will also suggest that the lower doses should be considered for men, the stronger recommendation for reduced dosage in women underscores the clear sex-associated differences in zolpidem pharmacokinetics observed in studies.

The FDA has also pointed out that the risk of impairment with modified-release formulations of zolpidem (Ambien CR and generics) is greater than the risk with immediate-release formulations.2 Accordingly, the agency announced in May 2013 that patients who take modified-release formulations, either 6.25 mg or 12.5 mg, even if they then sleep for the required 8-hour period, should refrain, for the day subsequent to using the drug, from driving or engaging in any activity that requires full alertness.3 This recommendation reflects not only the higher zolpidem content in the modified-release formulation but also the ability of the modified-release design to prolong the period of drug exposure.

Although the evaluation of driving impairment caused by prescription drugs is not new, quantitative analyses of the relationships among drug dose, blood levels, and driving impairment, as illustrated in the approval of Intermezzo and the associated review of zolpidem products, are likely to be of growing interest (and perhaps debate). It is clear that performance on a driving test cannot be directly and quantitatively translated to driving risk, but similar data about effects on performance have been used to set standards for blood alcohol levels, and the tests of performance have considerable face validity. Certainly, these data are far more informative than reports of motor vehicle accidents, in which the relation to drug dose, the time between zolpidem ingestion and the accident, and the use of ethanol or other drugs is generally uncertain. The FDA has asked the makers of insomnia drugs to submit all available data addressing the risk of residual impairment after prescribed use, and the agency is currently analyzing these data.

It could be asked why the FDA did not leave the recommended doses unchanged and continue to warn patients to watch for driving impairment. A variety of new data have shown that people affected by impairment after taking zolpidem frequently do not recognize their impaired state; patient self-perception is not an adequate gauge for impairment. Among patients whose sleep needs are satisfied with the use of the lower doses, unnecessary risk can be avoided, and as the labels point out, patients whose symptoms do not respond to the lower doses can be given the higher doses. The sex-specific labeling revisions reflect an evidence-based approach to risk management and dose individualization.

Source: NEJM

 

Germany launches investigation into human trials scandal.

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Germany’s pharmaceutical sector will cofund an investigation following claims that East German patients were recruited without proper consent into drugs trials. Rob Hyde reports from Bremen.

Medical historians from Berlin’s Charité hospital have begun an investigation into drug industry clinical trials done in the former German Democratic Republic (GDR) in the 1980s after allegations emerged to suggest that there might be ethical issues with the studies.

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A recent report by the German magazine, Der Spiegel, claims to have obtained records that prove that major drug companies such as Bayer, Hoechst, and Roche, made huge payments to the GDR to undertake clinical trials in East Germany. Governed by the Socialist Union Party of Germany (SED) and its hard-line Marxist-Leninist ideology, the cash-strapped communist regime is supposed to have allowed these drugs firms to test more than 600 products on more than 50 000 individuals. Most of these participants allegedly had no knowledge they were taking part in clinical trials, during which some patients died.

The magazine claims to have gained access to a mixture of unpublished files belonging to individual doctors and three state institutions of the Soviet-backed GDR. These include East Germany’s Health Ministry, its Institute for Drug Regulatory Affairs, and even its feared Ministry for State Security, the notorious Stasi.

Speaking to The Lancet, the director general of the Association of Research-Based Pharmaceutical Companies (vfa), Birgit Fischer, said it was necessary to actively engage in the investigation to establish facts. “So far there are no confirmed cases of illegal or illegitimate practices. It is for exactly this reason that we are engaging in the research project: to find out what really happened—no questions should remain open in the end.”

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“We therefore definitely must research all of this. There needs to be a really open but also fair debate. In Germany the debate simply consists of unclear claims and accusations so far, and the issue of clinical trials has been scandalised. It is a very prejudiced approach to the issue.”

The scientific investigation will be overseen by the German Federal Ministry of the Interior (BMI). While the BMI will fund 70% of the project, the remaining 30% will be split between four parties. These include the vfa, the Federal Foundation for the Reappraisal of the SED Dictatorship, the Berlin Chamber of Commerce, and the German Medical Association (BÄK).

Speaking to The Lancet, president of the BÄK, Frank Ulrich Montgomery said the controversial Spiegel article should not be considered gospel. “Bayer tested nimodipin in the GDR, and the magazine claimed that this left the patients [with addiction to alcohol] suffering from acute delirium, and therefore incapable of comprehending the situation they were in. But to me it is clear that they were disorientated as they were undergoing a special form of detoxification. Had they not received drugs to reduce blood pressure in the brain then they would have endured an extremely rough, unpleasant time.”

“In Germany, if there is a claim made, then a form of damage must be proven. But in this case, based on the information we have at the moment, I cannot see any. We just need more information and more facts. None have really been provided here.”

Germany’s drug industry is constantly stressing the importance of establishing facts and also their commitment to engaging in a debate. When approached by media, however, individual drugs companies are largely refusing to give interviews in which these facts can be debated. Though not prepared to discuss the trial directly, in a brief written statement, Helmut Schäfers, director of communications for Bayer Vital GmbH, stated that “all clinical trials were and are conducted by Bayer in accordance with globally agreed standards”.

The statement reads: “In as far as clinical studies commissioned by our company were carried out in the former GDR, we assume that this took place in accordance with the Declaration of Helsinki and the regulations of the Pharmaceutical Act of the former GDR.”

Other pharmaceutical companies have been more specific about the level of consent that was secured for the trials. Although declining a request for an interview, Nicole Gorfer of Roche Communications and Public Affairs, supplied a detailed, lengthy written statement relating to the activities of Boehringer Mannheim, now part of the Roche group. It confirms the occurrence of two clinical trials into the prevention of “anaemia of prematurity” with NeoRecormon (epoetin beta), a hormone that stimulates the development of red blood cells. One of these two studies took place at the Charité study centre in East Berlin.

The statement reads: “According to the relevant publication (Obladen et al 1991, Contrib Nephrol 1991; 88: 314—326), each study centre received approval from its competent ethics committee to conduct this study and enrol patients, and informed parental consent was obtained for all 93 preterm infants enrolled.”

One of the most infamous cases in the controversial trials involves Hoechst AG, which has since merged with Sanofi. Also declining to be interviewed directly, in a lengthy, detailed written statement, Miriam Henn, Vice President for Communications for Sanofi-Aventis Deutschland GmbH, confirmed that according to “documents from the former Hoechst AG which are in our archive, East German doctors conducted a small double-digit number of clinical studies”.

The statement reveals that nine active agents were tested to determine their effectiveness and tolerability as medication: ramipril, ramipril in combination with piretanide, ramipril in combination with felodipine, cefotaxime, pentoxifylline, glimepiride, roxatidine, buserelin, and insulin.

It reads: “The doctors involved in the studies were obligated to inform the participants of their objective and potential risks in advance. The studies also complied with the standards applicable at the time. The safety of patients has always had and will always have top priority for us.”

Critics of Hoechst say that this claim cannot be true because of deaths during the company’s clinic trial using Trental—a drug today used to help red blood cells flow through blood vessels to the legs and feet.

However, Hoechst’s statement reads: “In both former GDR study centers 21 patients were included. In the Trental group of the multinational study 12 patients died but only two of them came from the former GDR.”

Though the controversial article in Der Spiegel quotes the vfa director Ulrich Vorderwüllbecke as saying “I don’t want to see these kinds of investigations [into clinical trials] here”, just weeks later the same organisation announced it was cofunding the investigation. For some people this turnaround is because the magazine article was the start of a new process of finally exposing the sinister truths of GDR life. Rainer Wagner is the chairman of the Union of Support Groups for the Victims of Communist Tyranny. He attempted to flee East Germany at age 15 years, and in 1967 was imprisoned for 14 months for alleged “violent breach of the border”. He tells The Lancet that the pharmaceutical industry should be prepared to apologise for its involvement in these trials. “We were very grateful for this research [in Der Spiegel]. Human trials are just one of the things this unjust system did for money and it will only start to come out with articles like this. One doctor led the ramipril drug trial and it ended in patient deaths but today he is president of the State Chambers of Physicians in Thuringia. It’s all been completely covered up. IKEA has apologised for what it did in East Germany—forcing political prisoners to make Billy cupboards. The pharmaceutical industry should do the same.”

For the German Association of Research-Based Pharmaceutical Companies, however, at present issuing an apology is neither appropriate nor possible, according to director general Birgit Fischer. “It is not possible to offer an adequate reaction if it is not clear what one is supposed to be reacting to. Obviously in such a case we would not simply sweep this issue under the carpet. A reaction must be given if appropriate but it must be clear—a reaction to what, exactly?”

“Again we need to establish clear facts first. We must also remember we are talking about seriously ill patients here, and as harsh as it may sound, most or all of them may have died from their illness rather than due to their trial participation. At the moment, clinical trials are being discredited, although they can give people new hope that they will improve their health and quality of life”, concludes Fischer.

The formal investigation into the trials started on June 15 and is expected to last 2·5 years.

Source: Lancet

Universal flu jab ‘edges closer’.

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A way of creating more effective vaccines which could protect against a broad range of flu viruses has been reported by US researchers.

A different seasonal flu jab is produced every year as the virus is a constantly shifting target.

This animal study, published in the journal Nature, showed a single jab could protect against multiple strains.

Flu scientists said it was an important advance, but a vaccine which could defeat all flu was a long way off.

While there are different strains of flu circulating each year, there are bits of the flu virus which do not change.

Many groups of researchers believe that targeting these weak spots could lead to a single, universal flu vaccine.

Synthetic biology

The normal seasonal flu jab is made by growing the virus in chicken eggs. It is then inactivated and injected into people to train the immune system to fight off that virus.

A group at the pharmaceutical company Sanofi used a different approach to design a new protein which was half virus.

Spikes which stick out from the surface of the virus, which hardly vary between strains, were fused with a ‘transporter protein’ which is naturally found in blood.

Groups of these hybrid proteins then spontaneously formed tiny spheres, which were tested in ferrets.

Flu researchers use ferrets as they are can be infected with human viruses, which results in similar symptoms.

The vaccine gave the animals immunity against multiple batches of flu ranging from viruses circulating in 1934 through to 2007.

Dr Gary Nabel, the chief scientific officer at Sanofi, told the BBC: “We think this is a step down the path towards a universal vaccine. It’s not a universal vaccine yet.

“There’s lots of research in the early phases and this looks as good as anything out there.”

Not everything

The spike used in the vaccine was haemagglutinin, but there are many different types of haemagglutinin. It is how viruses are classified – swine flu in 2009 was H1N1, with the H standing for haemagglutinin.

This vaccine was designed to protect against H1 flu viruses. It would not protect against others such as the current bird flu in China, H7N9.

Prof Sarah Gilbert, who works on universal vaccines at Oxford University, told BBC News: “It is an improvement on the current vaccine. It’s not a ‘universal vaccine’ but it’s definitely a step in the right direction.”

She said it might be able to get over the problems of “mis-match” when there are differences between the seasonal vaccine and the flu being targeted.

However, the vaccine has not yet been tested in people. Clinical grade vaccine has not yet been developed so even safety trials are thought to be a year away.

There is a risk that the flu virus could find ways to evade the vaccine.

Prof Wendy Barclay, from Imperial College London, said: “I think the important question to explore in the field now is…will the virus be able to escape by ‘drift’ like it does each year to our natural antibody response, or can it be ‘pinned in’ by the immune response induced by this new era of vaccines?”

Dr Nabel agreed that viruses could be difficult to pin down: “It is like squeezing a balloon. You squish one place and another pops out. The viruses are very clever and under pressure they find a new way to escape.”

Source: BBC

groundr�t’8(� �� yle=’font-size:13.0pt; font-family:”Arial”,”sans-serif”;color:#333333′>In contrast, previous research on the link between intelligence and reaction times, colour discrimination and sensitivity to pitch found only a 20-40% correlation.

 

But the ability to ignore background movements is not the only indicator of intelligence.

“Because intelligence is such a broad construct, you can’t really track it back to one part of the brain,” says Duje Tadin, who also worked on the study.

“But since this task is so simple and so closely linked to IQ, it may give us clues about what makes a brain more efficient, and, consequently, more intelligent.

“We know from prior research which parts of the brain are involved in visual suppression of background motion.

“This new link to intelligence provides a good target for looking at what is different about the neural processing, what’s different about the neurochemistry, what’s different about the neurotransmitters of people with different IQs.”

Source: BBC

Amgen Agrees to Pay $762 Million in Drug Marketing Case.

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drug-pays

In recent years, drug companies have paid out billions in fines to settle various federal, state and civil lawsuits.

Among the charges is promoting drugs illegally for off label use, which is common, even when it puts patients lives at risk.

It’s been said that imposing fines – even those that approach $1 billion or more – is simply not enough to deter this type of criminal behavior, as the drug company executives sitting at the helm are not held personally accountable (or subject to personal prosecution) and jail time.

This appears to be precisely the case, as time and time again drug companies are allowed to promote drugs for uses that could actually harm patients, or engage in other illegal, criminal activities, and they receive what amounts to a slap on the wrist as punishment.

Two drug giants, Amgen and Sanofi, are the latest to add hundreds of millions in settlement monies to the growing stash …

Amgen to Pay $762 Million in Criminal Penalties for Illegal Drug Marketing

According to one U.S. attorney, Amgen was “pursuing profits at the risk of patient safety”1 by selling and promoting the drug for unapproved uses. Prosecutors alleged that Amgen had promoted the anemia drug Aranesp to treat cancer patients not undergoing chemotherapy (the drug is only approved for those receiving chemotherapy). A later Amgen study actually showed that giving cancer patients who were not receiving chemo Aranesp increased their risk of death.

The company also was federally charged with promoting larger, but less frequent, injections of Aranesp as a way to edge out competing drugs – even though the U.S. Food and Drug Administration (FDA) had turned down Amgen’s requests for this approval, citing inadequate safety studies. In fact, one study actually found giving the drug at higher doses may increase cardiovascular risks …

Drug Promoted Off-Label Despite Research Showing Increased Heart Risks

In 1998, the Normal Hematocrit Trial was published, which explored giving higher doses of drugs to dialysis patients in order to boost their red blood cell count above those generally achieved with transfusion.2 The study found that patients receiving the higher drug dose were dying or having heart attacks at a higher rate than those receiving the lower dose; the trial was actually halted because of this.

However, rather than sounding an alarm bell, when the study was published the authors downplayed the danger, calling the increased death and heart attack rate “not significant.” And while no difference was found in quality of life between patients receiving the higher or lower dose, this was not noted in the published study. (Four of the study’s eight authors were employed by Amgen, and two have served as consultants.)

As the years went by, health care providers and the drug companies continued to profit from the ever-rising doses of these drugs being prescribed – despite continued studies coming out questioning their safety. It wasn’t until years later, in 2011, that the FDA put out a safety announcement calling for more conservative dosing of the drugs “because of data showing increased risks of cardiovascular events.”3

The New York Times further reported on Amgen’s charges:4

“A document summarizing the charges says that while sales representatives were not supposed to initiate discussions of off-label uses, they were trained to elicit questions from doctors. Such questions would provide the “necessary cover” for the sales representatives to provide the doctor with studies supporting the off-label use. Amgen referred to this as “reactive” marketing, the document said.

Amgen also managed to list the unapproved uses in a reference called a compendium. Medicare is required to pay for off-label uses of cancer drugs listed in an approved compendium. The compendium system is intended to make drugs more easily available to cancer patients, but critics say the compendiums do not adequately review the evidence.”

To settle the charges, Amgen has agreed to pay $612 million for civil litigation, along with $136 million in criminal fines and forfeit $14 million. The company has also agreed to sign a Corporate Integrity Agreement that requires executives to certify compliance with regulations, which would theoretically make it easier to prosecute them personally for any future offense. This is, unfortunately, just the latest drug scandal to be brought to the public’s attention… and it surely won’t be the last.

Sanofi to Pay $109 Million to Settle U.S. Kickback Charges

You might remember drug maker Sanofi, as I recently ran articles on them describing the revolving door between federal agencies and the drug companies. The chief and major science officer from the U.S. National Institutes of Health (NIH) took jobs at Sanofi as their president and chief scientific officer. Now the company has agreed to pay $109 million to resolve allegations that it gave free drugs to physicians as a form of kickbacks, which violates the False Claims Act.

The company allegedly gave out thousands of free “samples” of the arthritis drug Hyalgan that were contingent on future purchases and essentially used to lower the drug’s effective price. Sanofi then submitted false average sales price reports, which are used to determine reimbursements rates from Medicare and other government health programs, thereby causing the government to pay inflated rates for the drug.5

In this case no criminal charges were filed and, other than the paltry $109 million settlement, Sanofi only has to enter into a Corporate Integrity Agreement with the government that is supposed to leave them under enhanced scrutiny.

The Top 10 Drug Company Settlements

Big Pharma lawsuits, especially those that settle in the hundreds of millions or billions, are intended to compel these criminal corporations to straighten out, abandon their fraud and deception, their kickbacks, price-setting, bribery and all other illegal sales activities in favor of looking out for public health, which to date has been clearly ineffective.

Most of these settlements amount to a mere slap on the wrist for the drug company, which typically will continue right along with their deceitful behaviors. This is evidenced by the stunning frequency with which these major settlements occur:6

  1. 2007: Bristol-Myers Squibb paid $515 million for illegally promoting its atypical antipsychotic drug Abilify to kids and seniors (despite a black box warning that warned of potentially fatal side effects in the elderly). Other accusations included giving payments, kickbacks and expensive vacations to medical professionals and pharmacist to dispense its drugs.
  1. 2010: AstraZeneca settled for $520 million for trying to persuade doctors to prescribe its psychotropic drug Seroquel for unapproved uses ranging from Alzheimer’s disease and ADHD to sleeplessness and post-traumatic stress disorder (PTSD). Using Seroquel for improper use has been linked to an increased risk of death.

Company executives also promoted the drug for weight loss, highlighting one favorable study while burying others that linked it to substantial weight gain.

  1. 2007: Purdue Pharma paid $634.5 million for fraudulently misbranding Oxycontin, and suggesting it was less addictive and less abused than other painkillers. The company was charged with using misleading sales tactics, minimizing risks and promoting it for uses for which it was not appropriately studied.
  1. 2012: Amgen, the makers of anemia drugs Aranesp and Epogen, has been accused of handing extra profits to doctors who prescribe the drugs (by overfilling vials, then allowing doctors to charge insurance companies for drugs they got for free). Other accusations include misconduct involving claims of safety and efficacy, marketing, pricing and dosing of the drugs. Amgen has agreed to pay $762 million to settle the suits.
  1. 2011: Merck settles for $950 million to resolve fraudulent marketing allegations and safety claims related to Vioxx. Vioxx was pulled from the market in 2004, after it was shown to double the risk of heart attack and stroke. In addition to the $950 million, Merck paid hundreds of millions more to harmed patients and their families (Vioxx contributed to causing heart attacks in up to 140,000 people, half of which were fatal).
  1. 2009: Eli Lilly pays $1.4 billion for promoting Zyprexa for off-label uses, often to children and the elderly, and not properly divulging side effect information. For instance, Zyprexa was marketed as a sleeping aid for the elderly because one of its side effects is sedation, even though the drug also increases the risk of death.
  1. 2012: Abbott Laboratories settles for $1.5 billion for aggressively promoting their seizure drug Depakote for off-label use in elderly dementia patients, despite lacking evidence of safety or effectiveness (and a known increase of serious side effects, like anorexia, in the elderly).
  1. Currently pending: Johnson & Johnson will pay anywhere from $1.5 to $2 billion for illegal marketing of Risperdal and other drugs. The company not only heavily marketed drugs to children and the elderly despite inadequate evidence of safety or efficacy, they also hid data about drugs’ side effects.
  1. 2009: Pfizer pays $2.3 billion for marketing fraud related to Bextra, Lyrica and other drugs. Charges included marketing drugs to doctors for uses for which they had not been approved and giving kickbacks to doctors and other health care professionals for prescribing their drugs. This was Pfizer’s fourth settlement numbering in the multimillions in less than a decade.
  1. 2012: GlaxoSmithKline (GSK) to pay $3 billion for illegal marketing of Paxil and Welbutrin and downplaying safety risks of Avandia, among other charges. The company hid data about drug risks, marketed drugs for unapproved uses, and paid doctors (or gave them lavish gifts like expensive vacations) for prescribing their drugs. One of the most high-profile accounts involved television celebrity Dr. Drew, who reportedly received $275,000 from GSK to promote Welbutrin to treat sexual dysfunction associated with depression even though it hasn’t been proven effective for this purpose.

Are You Putting Your Health in the Hands of Criminals?

If you rely on drugs to stay well, or believe that if you get sick one day you’ll simply take a medication to “get better,” it’s worth recognizing that the same companies that are manufacturing and promoting those drugs have probably been convicted of criminal and fraudulent charges. You might want to reconsider your decision in light of these circumstances.

Putting your health, your very life, in the hands of these drug companies is a frightening prospect because the leading pharmaceutical companies are also among the largest corporate criminals in the world, often behaving as if they are little more than white-collar drug dealers. As these companies have shown time and again, they consistently put profits above human health … and this includes your health.

Adding salt to the wound, most of the top-selling drugs treat conditions that are better treated with lifestyle changes, healthy food and other forms of natural healing!

Source: Dr. Mercola