Diabetics – Drug manufacturers seek to expand the range of treatments.

Drug manufacturers seek to expand the range of treatments

Three companies have long dominated the commercial battle over insulin. For nearly a century since it was first developed, the precursors of what are now Novo Nordisk, Eli Lilly and Sonofi  have continued to corner growing global sales currently totalling $20bn a year. From animal to human insulin, and increasingly to longer-lasting and more convenient “analogue” versions using ever more discreet pen injectors, the “big three” have maintained their influence and introduced new products, even as their rivals have sought to win a niche.

If Eli Lilly historically controlled insulin in North America, Novo Nordisk of Denmark focused on exports into Asia, while Hoechst – now part of Sanofi – distributed in central Europe. Chris Viehbacher, chief executive of Sanofi, says: “Ninety per cent of production capacity comes from three companies. It’s a big investment. It’s quite difficult to make insulin, and we produce it by the ton.”  “Insulin is a high-volume, low-cost drug,” says Lars Sorensen, chief executive of Novo Nordisk. “In order for people to engage in this area, they need to make very high upstream investment in clinical programmes, active ingredient manufacturing, downstream formulation and filling. Patients and the market place are rather conservative. That gives a margin that favours the incumbent.”

He argues that, if anything, potential generic producers have withdrawn from the race in recent years. Pfizer last year scrapped a partnership it had forged with Biocon of India to produce “biosimilar” insulins, for instance. Teva of Israel, the world’s largest generic company, has moved slowly. Ironically, some of the greatest competition may yet come instead from the original trio of manufacturers. Eli Lilly has indicated that it is working on a version of Sanofi’s product Lantus, on which the patent expires in 2015. Sanofi itself is also preparing a new formulation, U300. Merck, the other leading global diabetes specialist through sales of its dipeptidyl peptidase-4 (DPP-4) inhibitor oral drug Januvia, is eyeing the market for insulin, too.

Jeffrey Holford, pharmaceutical analyst with Jefferies, questions whether there will be significant price cuts as a result of such rival versions. He notes that while volumes have grown only slowly in the US over the past year, prices have risen more sharply. “We doubt Lilly will want to destroy pricing for Lantus,” he says. “We continue to believe that this will be a branded generic market. New producers will not attack on price but join in and enjoy the large market size.”

Not all the news in recent months has been positive for pharmaceutical companies specialising in diabetes. In February, Novo Nordisk’s long-acting insulin Tresiba was stalled by US regulators – despite approval by their counterparts in Europe and Japan – over concerns that it could cause heart problems. Fresh studies are likely to delay its launch for three years. While metformin and other low-cost generic pills still dominate pre-insulin treatment by volume, investment continues into newer drugs despite setbacks over safety and debates about their incremental benefit.

Earlier this decade the drug class called thiazolidinediones or TZDs, designed to prevent the onset of type 2 diabetes, was undermined. This was after GlaxoSmithKline’s Avandia and Takeda’s Actos were both withdrawn, following safety warnings over cardiac problems and bladder cancer, respectively. Safety concerns linked to pancreatitis have held back sales of the class of injectable hormones called glucagon-like peptide (GLP)-1 agonists, led by Byetta (which is jointly controlled by Bristol-Myers Squibb and AstraZeneca after their purchase of Amylin) and Novo Nordisk’s Victoza.

DPP-4 inhibitors or gliptins, led by Merck’s blockbuster Januvia, are the largest class of diabetic treatments other than insulins. Yet the growth in their sales has slowed recently in the US. Mr Holford points to concerns over safety for the entire therapeutic class – notably AstraZeneca and Bristol-Myers Squibb’s Onglyza. He says there is a new competitive threat from sodium glucose transporter (SGLT)-2 inhibitors, led by Johnson & Johnson’s Invokana, which remove glucose from the bloodstream.

An aspiration for drug companies in diabetes treatment would be the development of oral insulins. Many see that as still a long way off, because of difficulties in preparing a complex biological medicine in the form of a pill that can be swallowed and efficiently absorbed. Pierre Chancel, head of diabetes at Sanofi, says: “People have been talking about it for at least 20 years and will continue to do so. Insulin is a big peptide and it is difficult to formulate into a pill.” Companies are still seeking to expand the range of treatments to prevent or slow the growth of diabetes. Novo Nordisk is seeking regulatory approval to extend the use of the active ingredient in Victoza for weight loss.

Yet – as with other weight loss drugs including Vivus’ Qsymia and Arena’s Belviq launched in recent months – there is considerable scepticism about the size of the market. The data so far show the costs are high and the effects are marginal and quickly reversible.

Prof. HL