A period of careful eating and regular exercise can stave off diabetes for a decade, a study suggests.

US researchers followed up nearly 3,000 overweight people who had taken part in a three year diabetes prevention programme.

The group had initially been divided into three – assigned either to a diet and exercise programme, the diabetes drug metformin or a placebo.

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The Lancet report notes it was the dieters who reaped the most benefit.

All three groups were given access to ongoing lifestyle coaching once the initial three year trial had ended.

That trial, carried out by the US-based Diabetes Prevention Program Research Group, had shown a diet aimed at achieving 7% weight loss, combined with half an hour of exercise five days a week, reduced the risk of developing Type 2 diabetes by 58% compared with the placebo group.

The group on metformin, a drug which has been used to treat the condition since the 1950s, saw their risk decline by nearly a third.

In the seven years after the trial ended, both the drug and placebo groups – now also eating more carefully and exercising – saw the rate of diabetes fall.

But the most significant drop was among those who had started out on a diet and exercise regime – their risk was over a third lower than the placebo group.

In an accompanying editorial, Dr Anoop Misra, a specialist in diabetes in New Delhi, described the prevention of the disease as “a long and winding road”.

‘No short cut’

Dr Misra said: “There seems to be no short cut, and a persistent and prolonged intensive lifestyle intervention seems to be the most effective way to travel on it.”

But he warned it could not be the only measure: “We need more effective drugs for those who cannot follow intensive lifestyle therapy because of infirmity.”

Type 2 diabetes usually appears in people over the age of 40, however increasing numbers of children are being diagnosed with the condition, some as young as seven.

Although obesity is a risk factor, not all people with type 2 diabetes are overweight.

Dr Iain Frame, head of research at Diabetes UK, said: “It is fascinating to read about the 10-year follow up studies and of the importance of lifestyle interventions, with or without metformin, in the prevention of Type 2 diabetes even after 10 years.

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“There is clearly no easy route to take to prevent Type 2 diabetes but indications are that with further research into the long-term benefits of good dietary advice, physical activity and, where necessary drug therapies, we may be a step closer into helping people at high risk of developing Type 2 diabetes modify their lifestyle choices that are sustainable in the longer term.”

Source: BBC NEWS

Popularity: 2% [?]

In the first Phase III study of Bristol-Myers Squibb and AstraZeneca’s diabetes drug, dapagliflozin met both primary and secondary endpoints. When used with the common diabetes drug metformin, the drug reduced blood glucose levels and fasting plasma glucose  in patients with type 2 diabetes inadequately controlled with metformin.

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Dapagliflozin is part of a new class of drugs called SGLT2 inhibitors. The protein SGLT2 helps the body retain glucose for its energy requirements. But for patients with diabetes, glucose retention leads to persistent high blood sugar. SGLT2 inhibitors suppress this protein so that excess glucose is excreted from the body rather than reabsorbed.

Analysts project dapagliflozin sales at $1.5 billion, though they will keep an eye on potential safety issues with the drug. “Dapa’s (dapagliflozin’s) unprecedented efficacy offering for an oral anti-diabetic agent–with what we see as a manageable safety profile–puts it on a trajectory to be a risk-adjusted global blockbuster,” UBS said in a research note, as quoted by Reuters. Barring any problems, approval is anticipated in 2010 or early 2011.

Source: FierceBiotech

Popularity: 2% [?]

The FDA said today that Merck’s diabetes drug Januvia may be associated with pancreatitis, a serious inflammation of the pancreas that can lead to hospitalization and, in rare cases, death. Merck said that the data suggest the drug doesn’t cause pancreatitis.

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This is the second time in just over a year that a popular, new-ish diabetes drug has been linked to pancreatitis — the previous case was Byetta, which is co-marketed by Amylin and Eli Lilly. In that instance, several deaths were reported.

The FDA said today it had received 88 reports of pancreatitis in patients taking Januvia and Janumet, a related drug that combines Januiva with the diabetes medicine metformin. The agency didn’t report any deaths in cases of pancreatitis in patients taking the drugs, but 66% of the cases did require hospitalization. In 21% of cases, pancreatitis occurred within 30 days of starting Januvia or Janumet; 53% of the cases resolved once after the drug was discontinued.

Merck said that data from clinical trials that included more than 6,000 people, as well as reports that have emerged since the drug has been on the market, don’t show an increased risk of pancreatitis associated with Januvia. The statement notes that simply having diabetes increases the risk of the disorder.

Amylin and Lilly have been named as defendants in Byetta cases brought by 110 plaintiffs in cases primarily related to pancreatitis, Amylin said in its most recent quarterly report. Byetta sales fell slightly in the first half of this year, to $332.8 million from $336 million in the year-earlier period.

Byetta and Januvia are different classes of drugs. But they work in related ways. Januvia slows the breakdown of a hormone known as GLP-1 and a related hormone; Byetta mimics naturally occurring GLP-1.

Merck’s sales of Januvia and Janumet totaled more than $1 billion in the first six months of this year.

Source: The Wall Street Journal

Popularity: 3% [?]

Eli Lilly, Amylin and Alkermes reported Monday that patients with type 2 diabetes who took exenatide once weekly had a significant reduction in A1C levels compared with those who took sanofi-aventis’ Lantus (insulin glargine). The companies also said that use of the long-lasting GLP-1 analogue in the head-to-head trial resulted in a significant reduction in weight versus sanofi-aventis’ product.

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The DURATION-3 study enrolled 467 patients with type 2 diabetes who were not achieving adequate glucose control with metformin alone or in combination with a sulphonylurea. Patients were randomly assigned treatment with either exenatide once weekly, or once-daily doses of Lantus. Following the 26-week treatment period, data for the primary endpoint showed that A1C levels were reduced by 1.5 percentage points from baseline among those administered exenatide once weekly, compared to a drop of 1.3 percentage points for Lantus-treated patients. Both groups started with a baseline A1C level of 8.3 percent.

Furthermore, findings at 26 weeks showed that treatment with exenatide once weekly resulted in a mean weight loss of 5.8 pounds, compared with a mean weight gain of 3.1 pounds in the Lantus group, the companies stated. Eli Lilly, Amylin and Alkermes submitted the treatment for review by US regulators earlier this year.

The twice-daily version of the diabetes drug, Byetta, was approved in 2005 and generated global sales of $751 million last year.

Source: FirstWord

Popularity: 3% [?]

AstraZeneca and Bristol-Myers Squibb announced Thursday that their application for Onglyza (saxagliptin) received a positive opinion from the EMEA’s Committee for Medicinal Products for Human Use for the treatment of type 2 diabetes. The DPP-4 inhibitor has been recommended for adults as an add-on therapy with metformin, a thiazolidinedione or a sulphonylurea.

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The companies said the positive opinion was reached after the CHMP reviewed data from a clinical development programme that included six Phase III trials assessing the safety and efficacy of Onglyza as a once-daily therapy. These studies involved 4,148 patients with type 2 diabetes, including 3,021 patients treated with Onglyza.

In the US, the drug received backing from an FDA advisory panel in April. Later that month, the agency announced that it was extending its review of the drug by three months to July 30.

Source: FirstWord

Popularity: 3% [?]

Takeda announced Thursday that it will delay the EU filing of experimental type 2 diabetes drug alogliptin, as well as a treatment combining the compound with Actos (pioglitazone), by about two and a half years to 2012 in order to conduct an additional long-term clinical study on the DPP-4 inhibitor. Company spokesperson Toshiyuki Ikeuchi said “the test would help us win approval with more certainty.”

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The two-year study will enrol almost 2500 subjects with type 2 diabetes, whose blood glucose level is inadequately controlled with metformin, and will evaluate “alogliptin compared to glipizide when used in combination with metformin.”

The move follows an announcement earlier this year that the FDA, which is currently reviewing alogliptin and is scheduled to render a decision by June 26, requested more data for the drug. A Takeda spokesperson specified that the decision to conduct a new trial was made without prompting by EU regulators and said the trial will be separate from an additional study planned for the US market.

Commenting on the development, analyst Yo Mizuno of the Daiwa Research Institute said “the delay in Europe is not a surprise… It has been largely expected, as a delay in the US of one to two years has become the market consensus.”

Source: FirstWord

Popularity: 2% [?]

A common anti-diabetes drug may boost the potency of vaccines against cancer, research suggests.

Tests on mice found metformin, used for Type 2 diabetes, helps the body’s T-cells work more effectively.

These cells, the body’s key defenders against disease, “remember” former infections or vaccinations, enabling them to fight subsequent illness.

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Writing in the journal Nature, a US team said metformin appeared to improve this important memory of disease.

This ability to remember disease has been the subject of much research, but there has been little understanding of the cellular mechanisms behind it.

The team from McGill University and the University of Pennsylvania used an experimental cancer vaccine and found that when administered in mice, the diabetes drug appeared to improve the strength of the inoculation.

Diseases ‘linked’

Several studies in recent years have shown that people with diabetes may be more likely to develop certain cancers, although the exact nature of the relationship is unclear. Type 2 diabetes is associated with extra weight for instance, as are certain types of cancer.

But there also appear to be similarities between the basic chemical reactions which happen in the cells when affected by either of these diseases.

“Many genes involved in diabetes regulation also play a role in cancer progression,” said Dr Russell Jones of McGill’s Goodman Cancer Centre, one of the report’s author.

“There is also a significant body of data suggesting that diabetics are more prone to certain cancers. However, our study is the first to suggest that by targeting the same metabolic pathways that play a role in diabetes, you can alter how well your immune system functions.”

This is turn could help the body fight cancer more effectively with a vaccine.

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Cancer vaccines are still at an early stage, but ideally could help both stop the disease developing in the first place or treat it when it arises.

Dr Kat Arney, Cancer Research UK’s senior science information officer, said: “This is a fascinating piece of research, which sheds light on the complex links between the immune system, cell metabolism and cancer.

“At the moment, this research has only been done in mice and there is a long way to go before it can be applied to cancer patients, but it certainly holds promise for the future.”

Source: BBC NEWS

Popularity: 2% [?]

GlaxoSmithKline announced Tuesday that the company began late-stage testing of experimental GLP-1 agonist Syncria (albiglutide) for the treatment of type 2 diabetes. The Phase III programme will involve five studies and more than 4000 patients.

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The primary endpoint for all the studies will be the change from baseline in HbA1c compared with placebo and/or active comparators, such as metformin, sulphonylurea, thiazolidinedione, insulin and a dipeptidyl peptidase four inhibitor.

Other GLP-1 agonists include Eli Lilly and Amgen’s Byetta (exenatide) and Novo Nordisk’s experimental liraglutide, and WestLB analyst Simon Mather suggested that if both these drugs “swallow up the market then it might be quite hard to get market share, but if (Syncria is) shown to have a better safety profile and better efficacy, then potentially it could generate quite good revenue.”

Source: FirstWord

Popularity: 3% [?]

- The Six-Month Primary Efficacy Endpoint of the Study was met: Both Doses of Investigational Agent Safinamide Significantly Increased “ON” Time in Levodopa-Treated Patients With mid- to Late-Stage Parkinson’s Disease

- Secondary Efficacy Endpoints of the Study Analyzed to Date Were met in Both Safinamide Dose Groups

Merck Serono, a division of Merck KGaA, Darmstadt, Germany, and its partner Newron Pharmaceuticals SpA (SWX: NWRN) announced today that the first Phase III trial of investigational agent safinamide as adjunctive therapy to levodopa (study 016) met its primary endpoint by increasing daily “ON” time in mid- to late-stage Parkinson’s disease patients with motor fluctuations by 1.3 hours. “ON” time represents periods when Parkinson’s patients experience their best level of motor functioning.

The two safinamide treatment groups of the study (receiving either safinamide 50 mg orally once daily or safinamide 100 mg orally once daily as adjunctive therapy to levodopa) demonstrated a statistically significant increase of daily total “ON” time compared to placebo. Throughout the six months of the study, patients treated with both doses of safinamide experienced an average increase of “ON” time of 1.3 hours per day compared to baseline. Patients in the placebo group (receiving placebo in addition to levodopa and other anti-Parkinson therapies) reported an average increase of daily “ON” time of 0.7 hour compared to baseline. The differences between both safinamide dose groups and placebo were statistically significant with p-values of 0.008 (safinamide 50 mg daily) and 0.005 (safinamide 100 mg daily).

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“The results indicate that safinamide, when used adjunctively to existing dopaminergic therapies for study patients in mid-to-late stages of Parkinson’s disease, increases daily “ON” time of motor functioning,” said Dr. Bernhard Kirschbaum, Merck Serono’s Executive Vice President for Global Research and Development. “These results represent a further step toward our goal to provide patients and doctors with urgently needed new treatment possibilities in the Neurodegenerative Diseases therapeutic area.”

Dr Ravi Anand, Newron’s Chief Medical Officer, said: “These results are extremely encouraging. In addition to increasing “ON” time and reducing total “OFF” time, as well as “OFF” time after morning dose in patients with mid- to late-stage Parkinson’s disease receiving optimized treatment with drugs including levodopa, dopamine agonists, COMT inhibitors, anti-cholinergics and amantidine, the results indicate a statistically significant improvement of motor function. Previously reported results from Phase II and Phase III studies have shown improvement of motor symptoms in early Parkinson’s disease patients on dopamine agonist monotherapy. These results from both early and advanced Parkinson’s disease patients underline safinamide’s potential to be used as adjunctive therapy along the continuum of Parkinson’s disease.”

This Phase III study was a six-month (24-week), randomized, double-blind, placebo-controlled international trial. It enrolled 669 patients with mid- to late-stage idiopathic Parkinson’s disease (more than three years of disease duration) receiving stable doses of levodopa, who had motor fluctuations with >1.5 hours of “OFF” time(1) during the day. Additionally, patients may have received concomitant treatment with stable doses of a dopamine agonist and/or an anti-cholinergic drug. After a four-week levodopa dosage stabilization phase, study participants were randomized to one of the three arms of the trial (1:1:1) to receive either one of two different doses of safinamide (50 or 100 mg once daily: 223 and 224 patients, respectively) or matching placebo tablets (222 patients), as adjunctive treatment to their levodopa therapy. The primary efficacy endpoint of the study was the increase in mean daily “ON” time (“ON” time without dyskinesia plus “ON” time with minor dyskinesia) during an 18-hour period as assessed by patients’ recordings on diary cards.

Out of the 669 randomized patients, 89% of patients treated with safinamide completed the study (91% in the 50 mg dose group and 87% in the 100 mg dose group) compared to 89% in the placebo group. Over 90% of patients who completed the initial 24 weeks of treatment elected to enter a 78-week, placebo-controlled double-blind extension study, which is ongoing, to specifically assess the effect on dyskinesias as primary endpoint.

Secondary efficacy endpoints of this study were also met, including decrease in daily “OFF” time, decrease in mean “OFF” time following first morning dose of levodopa, mean change from baseline in the Unified Parkinson’s Disease Rating Scale (UPDRS)(2) Section III (motor) score during “ON” time and mean change in Clinical Global Impression of severity of disease and change from baseline (CGI)(3). The incidence of dropouts, serious adverse events or clinically notable events among the three groups of the study were comparable.

Full study results after completion of ongoing analyses will be submitted for presentation at upcoming scientific meetings.

Merck Serono has exclusive worldwide rights to develop, manufacture and commercialize safinamide in Parkinson’s disease, Alzheimer’s disease and other therapeutic applications, as per the agreement signed with Newron in 2006.

About safinamide

Safinamide, an alpha-aminoamide derivative that is orally formulated, is currently being developed by Merck Serono and Newron as an add-on treatment for patients with Parkinson’s disease. Safinamide is believed to have a novel dual mechanism of action based on the enhancement of the dopaminergic function (through reversible inhibition of monoamine oxidase-B [MAO-B] and dopamine uptake) and reduction of glutamatergic activity by inhibiting glutamate release.

About Parkinson’s disease

Parkinson’s disease is a degenerative disorder of the central nervous system that often impairs the patient’s motor skills and speech. Parkinson’s disease belongs to a group of conditions called movement disorders. It is characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia) and, in extreme cases, a loss of physical movement (akinesia). The primary symptoms are the results of decreased stimulation of the motor cortex by the basal ganglia, normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain. Secondary symptoms may include high-level cognitive dysfunction and subtle language problems. Parkinson’s disease is both chronic and progressive. It is estimated that more than 3 million people in the industrialized countries suffer from Parkinson’s disease.

About Merck Serono

Merck Serono is the division for innovative prescription pharmaceuticals of Merck, a global pharmaceutical and chemical group. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. Its North American business operates in the United States and Canada as EMD Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux(R), cetuximab), multiple sclerosis (Rebif(R), interferon beta-1a), infertility (Gonal-f(R), follitropin alfa), endocrine and cardiometabolic disorders (Glucophage(R), metformin); (Concor(R), bisoprolol); (Euthyrox(R), levothyroxine); (Saizen(R) and Serostim(R), somatropin). Not all products are available in all markets.

With an annual R&D expenditure of around EUR 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in autoimmune and inflammatory diseases.

About Merck

Merck is a global pharmaceutical and chemical company with total revenues of EUR 7.1 billion in 2007, a history that began in 1668, and a future shaped by 32,458 employees in 59 countries. Its success is characterized by innovations from entrepreneurial employees. Merck’s operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

(1) “OFF” time refers to the times when people with Parkinson’s disease have a decrease in the ability to move (hypomobility) and other symptoms that cause difficulty rising from a chair, speaking, walking or performing their usual activities. “OFF” episodes occur because the person’s dose of levodopa has worn off or suddenly stopped providing benefit.

(2) The Unified Parkinson’s Disease Rating Scale (UPDRS) is one of the most widely used rating scales used to follow the course of Parkinson’s disease. It is made up of 44 items, scored from 0 to 4, to establish individual patients’ mental status, activities of daily living, motor function and complications of therapy. These are evaluated by interview and clinical observation. Clinicians and researchers alike use the UPDRS and the motor section (Section III) in particular to follow progression.

(3) The Clinical Global Impression (CGI) is the general name for two rating scales that are commonly used in clinical trials. The CGI-C scale measures the change in the patient’s clinical status from baseline. The CGI-S scale measures global severity of illness at a given point in time. Both CGI-C and CGI-S use a 7-point scale.

Source: Merck Serono

Popularity: 7% [?]

Pfizer is currently leading cancer drug development related to the insulin-like growth factor (IGF) pathway, but faces competition from Roche, Amgen, ImClone, and others, investigators said. The IGF receptor target was identified roughly 20 years ago, and increasing evidence is now showing that the IGF pathway may be involved in human cancer progression. Read the full story

Popularity: 10% [?]