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Selected press releases - September 1st-14th 2004

News from the 40th Annual Meeting of the European Association for the Study of Diabetes (EASD)

According to WHO, there are some 130 million diagnosed diabetics in the world, a figure that is predicted to increase to 300 million by 2025. The majority of patients suffer from type 2 diabetes however type 1 diabetes (also known as insulin-dependent diabetes (IDDM) or juvenile-onset diabetes) is common affecting 10-15% of all diabetes sufferers.

The market for diabetes therapeutics is also rising with global sales reportedly topping $8.1 billion for the 12 months to September 2000, a 19% increase over the previous 12 months. Oral antidiabetic drugs, the leading class of drugs used to treat the disease, accounted for almost 63% of sales during this period, while sales of insulin stand at around 30%. Further increases are inevitable and the market for diabetes medications could exceed $20 billion by 2006.

Associated with diabetes is the metabolic syndrome, a cluster of three or more metabolic risk factors, including abdominal obesity, low levels of HDL-C, increased levels of triglycerides, raised blood pressure and raised blood glucose. The condition is very common; indeed in a recent report published by the analysts DataMonitor, it was estimated that approximately 115 million individuals suffer from metabolic syndrome in the seven major markets. This patient population is set to grow rapidly in response to the rising obesity and diabetes epidemics.

The EASD held last month in Munich heard data from the COmparative study with rosuvastatin in subjects with METabolic Syndrome (COMETS).

Correcting dyslipidemia in these patients represents a clinical objective for the treatment of metabolic syndrome and will increasingly contribute to the market for anti-dyslipidemics which achieved global sales of $21.7 billion in 2002, a growth rate of 12.5% over 2001. Due to the maturing of the market, evidenced by the increasing availability of generic statins, growth in this market has slowed in recent years however grow is expected to continue as only around 35% of people with high cholesterol are aware of their condition and only 12% are currently treated . Crestor represents one of the newest anti-dyslipidemics to reach the US and EU. First approved in the Netherlands in 2002 CRESTOR has since been approved in more than 60 other countries. FDA approval was gained in 2003. CRESTOR has been successful in penetrating these markets, having achieved around a 30% market share although concerns over safety led to slower initial uptake.

CRESTOR and Pfizer's Lipitor (atorvastatin), the dyslipidemia market leader and the world's largest revenue-generating product with 2002 sales of $8 billion are currently two of the key players in the battle for the dyslipidemia market. The COMETS study which compares the two agents head to head is thus of considerable interest.

This study showed that at the 20mg dosages AstraZeneca's CRESTOR (rosuvastatin) reduced LDL 49% and raised HDL by more than 10%, a statistically significant finding compared to another commonly prescribed statin, atorvastatin, in patients with metabolic syndrome. COMETS is the first international prospective study of statin treatment in people with the metabolic syndrome.

"The rising number of people with the metabolic syndrome has serious implications for public health," said Dr. Christie Ballantyne of Baylor College of Medicine and COMETS study investigator. "Results from this study show that CRESTOR is an effective medication for this 'higher risk' patient group, offering significant benefits by correcting abnormal lipid levels, both lowering bad cholesterol and raising good cholesterol." COMETS is a twelve-week study conducted in 68 centers in seven countries to compare the efficacy and safety of CRESTOR to atorvastatin and placebo. Results showed CRESTOR at 10mg reduced LDL-C by 42% after six weeks compared with 36% for atorvastatin at the same dose. CRESTOR 20mg, at 12 weeks, reduced LDL-C by 49% compared with 43% with atorvastatin 20mg [more]

A second study featured in this edition of PharmaNews Bytes from the EASD underlines the potential benefits of liraglutide, Novo Nordisk's investigational GLP-1 analogue as a novel treatment for type 2 diabetes.

Approximately 60% of diabetes patients do not achieve target A1C levels with their current treatment regimen. According to the ADA, patients with A1Cs above target are more likely to develop diabetes-related complications, such as kidney disease, blindness and heart disease. This evidence of suboptimal diabetes therapeutics has prompted the drug development sector to develop new and improved therapeutic options.

Oral antidiabetic drugs, the leading class of drugs used to treat diabetes, were up until recently synonymous with focused on metformin and sulphonylurea. The explosion of drugs available for controlling blood glucose began when Glucophage (metformin) became available in 1995, quickly followed by the approval of the insulinotropic agent Repaglinide in 1997 and the thiazolidinedione insulin sensitizers such as Avandia and Actos, which were both launched in 1999.

GLP-1 has attracted attention of researchers as a new approach to treat diabetes. GLP-1 is a gut hormone, also known as incretin, released after food consumption to stimulate insulin secretion and mimics of this hormone or molecules that prevent its breakdown are of considerable therapeutic potential as anti-diabetic drugs. Although GLP-1 demonstrates a number of potential benefits for type 2 diabetes, in its natural state it is rapidly broken down and is not practical as a therapeutic agent. Liraglutide is a once-daily long-acting analogue of this naturally occurring hormone and has already completed phase 2 clinical trials. Novo Nordisk expects to initiate phase 3 clinical trials by the end of 2004.

The study presented at the EASD showed that liraglutide, used alone or in combination with metformin, improves glycemic control (fasting serum glucose) compared to using metformin alone. In combination with metformin, liraglutide improved both glycaemic control (fasting serum glucose and HbA1c) and weight control when compared to glimepiride with metformin.

In the randomised, double-blind clinical study of 144 subjects with type 2 diabetes, liraglutide when used alone, resulted in a significant reduction in fasting serum glucose. In combination with metformin, liraglutide demonstrated improved glycemic and weight control compared with glimepiride and had a considerably greater impact on HbA1c than either agents administered as a monotherapy. These new findings add to the growing body of data supporting the potential of liraglutide as a promising and valuable therapy for treating type 2 diabetes, said Professor Michael Nauck, Diabeteszentrum, Bad Lauterberg, Germany, who presented these latest clinical data on liraglutide. He explained that the treatment of type 2 diabetes is complicated by the need to treat frequent co-morbid conditions such as obesity, but that none of the currently available medications result in weight loss [more on this story]

New data announced on Sept 7th showed that the oral insulin formulation, EXUBERA was effective and well tolerated in controlling blood glucose levels over a two-year period in patients with Type 2 diabetes.

The largest unmet need in the diabetes market is improved delivery of insulin. Currently, the predominant mode of insulin administration is subcutaneous injection, which is extremely unpopular among patients. This, in part, explains why only 13-28% of drug-treated type 2 diabetes patients receive insulin therapy. Analysts believe however that there will be a shift towards earlier initiation of insulin in the future, along with increased uptake, following the introduction of non-injected insulin. Consequently much effort is being placed on identifying new insulin delivery technologies, with inhaled and oral formulations both representing strategies under development. Most experience with inhaled insulin has been obtained using Exubera. Although phase III studies were completed in July 2001, further studies were initiated due to changes in FDA guidelines governing inhaled therapeutics. Following the report of this potential delay in regulatory filing, analysts predicted that launch would take place between 2002 and 2003, generating peak sales of anywhere between $250 million and $1.25 billion by 2006. Launch has yet to take place. In February 2004, Pfizer and Aventis submitted EXUBERA for review by the European Medicines Agency for marketing approval in the European Union. Interactions with the European regulatory authorities are ongoing.

The results, presented at the EASD, were combined results from two six-month clinical studies in patients with type 2 diabetes that were designed to assess the efficacy of EXUBERA when added to either sulfonylurea or metformin as compared to the combination of these oral agents without EXUBERA. Following the initial six-month trials, patients continued into extensions of up to an additional 18 months, where the primary objective was to assess long-term pulmonary safety. A total of 304 patients completed the two-year period.

During the two year period, patients in both the EXUBERA and the control treatment groups experienced declines in pulmonary function from baseline measured as FEV1and DLCO (carbon monoxide diffusing capacity). At week 24, small differences in declines in FEV1 and DLCO in favor of oral agents were observed. After two years of treatment, though, no significant differences between treatment groups were found. In addition, study results showed that HbA1c, an indirect way to measure blood glucose levels over time, decreased from 9.6% to 7.7% after two years for patients receiving EXUBERA and to 8.1% for patients in the control group. The most common adverse event in the Exubera-treated group was cough, which was considered to be transient and mild.

"These data show that small pulmonary function differences between the two groups occurred early after treatment initiation, had no identified clinical relevance, and did not progress with two years of continued inhaled insulin treatment," said Professor Manfred Dreyer, lead study investigator, Bethanien Krankenhaus, Hamburg, Germany [more on this story]

A second release on the same day announced results from Generex's pharmacodynamics and pharmacokinetics study of its oral insulin treatment, Oralin.

The purpose of the study was to compare Oralin, a buccal spray insulin formulation, with sub-cutaneous administration of insulin in healthy subjects. In this randomized crossover study, seven healthy volunteers received four different doses of buccal spray and a single dose of s.c. insulin under euglycemic clamp. Oralin had an earlier onset of action, more rapidly produced peak plasma insulin concentrations and had a shorter duration of action. The maximum insulin levels were comparable in the s.c. vs the highest dose of Oralin. In a second study presented at the EASD, Oralin was compared to s.c. regular insulin and to placebo spray in patients with type 1 diabetes. As in control subjects, Oralin had a faster onset and a shorter duration of action compared to s.c. regular insulin. It is mainly absorbed and effective in the first two hours after administration and therefore Oralin is well suited for the management of postprandial glucose excursions in type I diabetics [more on this story]

• News on asthma therapeutics presented at the European Respiratory Society [more]

• Stroke prevention - good and bad news [more]

• News from the European Association for the Study of Diabetes [more]

• Long-awaited FDA decisions on pain therapeutics [more]

Pharma NewsBytes features selected press releases recently featured on DailyUpdates and offers the reader a leisurely stroll through the past few weeks of activity from within the pharmaceutical industry.