A Growing Epidemic Drives an Expanding Market

The unfolding of a diabetes epidemic in the US wasrevealed in a report by the US Center for Disease Controland Prevention in 1999, which showed that the incidenceof diabetes rose by 6% in that year after increasing by33% between 1990 and 1998. These alarming statisticsappear to herald the arrival of an epidemic in the US and,indeed, in other parts of the world, where agingpopulations, unhealthy diets, obesity and sedentarylifestyles are major contributing factors to the rise indiabetic incidence. Approximately 17 million people inthe US and 150 million people worldwide have diabetes.The worldwide figure is predicted to grow to more than300 million by 2025. In the US, 90–95% of all diabetescases are type 2 diabetes. Unlike type 1 diabetes, which iscaused by destruction of pancreatic cells by the body’simmune system, type 2 is initially the result of a failureof peripheral tissues to respond to insulin. However, atlater stages of the disease there is damage to thepancreatic cells and the patient eventually becomesinsulin-dependent. Type 2 disease is no longerconsidered an adult-only disease. It is now being foundat younger ages and is even being diagnosed amongchildren and teens.

The massive predicted rise in market growth fordiabetes is spurring pharmaceutical companies to makesignificant investment in developing new drugs andnew formulations of old medicines to treat it. It has beenestimated that by the year 2011, sales of therapeutics fortype 2 diabetes alone will reach $US17.2 billion,representing an annual growth rate of 7% between 2001and 2011.

New Insulin-based Drugs

Exubera…A number of new-generation insulin products, capableof treating type 1 and type 2 diabetes, are currentlypoised to enter the diabetes market. Several inhaledinsulin formulations have reached late-stage clinicaltesting. The Pfizer/Aventis product Exubera hascompleted phase III studies for both type 1 and type 2diabetes in the US and Europe. The companies are usinga proprietary pulmonary drug delivery systemdeveloped by Inhale Therapeutic Systems’ (now calledNektar Therapeutics) to deliver insulin by inhalation.The system uses insulin as a dry powder in a hand-heldinhalation device, which converts the insulin powderparticles into an aerosol cloud without the need forpropellants. Exubera could be launched by 2005 if thesubmission of the planned NDA includes long-termpulmonary safety data that the companies believewould enhance the likelihood of obtaining a rapidreview by the US FDA. Lehman Market Analysis haspredicted that peak potential sales of the product couldreach $US1.5 billion in the US by 2013 and $US750million in the rest of the world.

…NN-1998…Another inhaled insulin product competing for a share ofthe global marketplace is NN-1998, currently in phase IIItrials for type 1 and 2 diabetes in the US. NN-1998 is beingdeveloped by Novo Nordisk and Aradigm Corporation,with the aim of providing patients with freedom frommealtime injections of short-acting insulin withoutcompromising efficacy. The product relies on Aradigm’sproprietary AERx drug delivery system, which convertsliquid insulin into a small-particulate insulin aerosol. An

April - May 200324

Teaching an Old Drug New TricksA New Generation of Insulins for Diabetes

The massive predicted rise in market growth for diabetes is spurring pharmaceutical companies to makesignificant investment in developing new drugs and new formulations of old medicines to treat it. It has been

estimated that by the year 2011, sales of therapeutics for type 2 diabetes alone will reach $US17.2 billion,representing an annual growth rate of 7% between 2001 and 2011.

Call +1 215-741-5201 or write to Pharmaceutical Innovation for additional information 25

electronic device delivers the particles locally to the lung orsystemically via the lung. Predicted peak sales of this agentin the US are estimated to be $US500 million in 2012 andrest of the world sales around $US250 million.

…and othersOther insulin-based medicines in late-stagedevelopment include Novo Nordisk’s insulin detimir(NN-304) and Aventis Pharma’s insulin glulisine. NovoNordisk submitted marketing applications for NN-304in the US and Europe at the end of 2002 for both type-1and type-2 diabetes. The fatty acid modification of theinsulin component of insulin detemir causes it to bind tohuman albumin, which inhibits the transport of insulinaway from the injection site and so prolongs its plasmahalf-life. Although it has to be administered by injection,studies show that it improves basal insulin levels

without causing a peak effect and has less day-to-dayvariation than conventional long-acting crystallineinsulin preparations. Worldwide peak sales in 2010 areexpected to net around $US500 million.

Insulin glulisine is a short-acting insulin analogue that isin phase III trials with Aventis Pharma in the US fortype-1 and type-2 diabetes. Insulin glulisine has a fasteronset and shorter duration of effect than normal insulin.The company plans to submit regulatory filings in theUS in 2003, and Lehman Market Analysis predicts thatworldwide sales should peak in the year 2012 nettingAventis around $US250 million.

In addition to these insulin-based products, there areseveral other non-insulin drugs in late-stage clinicaldevelopment for type-2 diabetes (table 1). ■

EMERGING ISSUES

Table 1. Non-insulin diabetes drugs in late-stage development

Development Drug Developer Indication stage

Awaiting Avandia GlaxoSmithKline A thiazolidinedione for improvement ofapproval (rosiglitazone maleate) glycemic control in type-2 diabetes

Ergoset (bromocriptine) Ergo Science Corp A dopamine receptor agonist for type 2 diabetes

Glipizide/metformin Bristol-Myers Squibb A sulfonylurea and biguanide for type 2 diabetes

Xenical (orlistat) Hoffmann-La Roche A lipase inhibitor for improvement of glycemic controlin overweight/obese patients with type-2 diabetes

Phase III AC-2993 (extendin-4) Amylin Pharmaceuticals A peptide for type-2 diabetes

Diovan/Starlix Novartis Pharmaceuticals An angiotensin II receptor antagonist and an (valsartan/nateglinide) insulinotropic agent for type-2 diabetes prevention

Metformin GR DepoMed A biguanide for type-2 diabetes

Metformin XT Andrix Corp A biguanide for type-2 diabetes

Xenical (orlistat) Hoffmann-La Roche A lipase inhibitor for the prevention of type-2 diabetes