Moving forward in diabetes

pharmafile | October 6, 2015 | Feature | Research and Development |  Novo Nordiak, diabetes 

As many as 387 million people worldwide are living with diabetes, and it is predicted that by 2035 more than 10% of the world’s adult population – 592 million people worldwide – will have diabetes. Yet the rule of halves means that only around 6% of people with diabetes live a life free from diabetes-related complications – which can include kidney failure, heart attack, stroke, blindness and amputations.

The global market for diabetes care products amounts to £27.5 billion ($41 billion). The market has grown by around 12% annually in the last decade and is expected to experience continued solid growth driven by an increased prevalence of diabetes and the need for better treatments. Of this global market, insulin accounts for 55%, oral diabetes products for 38% and GLP-1 products for 7%.

Much of the market is dominated by type 2 diabetes, which affects 90% of people with the condition. Globally, the type 2 diabetes therapeutics market value will increase from $23.5 billion in 2014 to an estimated $39 billion by 2021, according to Global Business Intelligence.

New drug launches

However this level of market growth will be under threat in the coming years as government cost-cutting measures are expected to continue. Moreover, the diabetes market is well developed, diagnosis rates are high, birth rates low and market leaders Novo Nordisk already has an insulin market share of 48% measured by volume. This means there are limits as to how much Novo Nordisk – and other companies operating in diabetes – can grow in Europe.

For Novo Nordisk, the key to accelerated growth is primarily expected to be gained from its insulin degludec product Tresiba as it becomes available to more patients, and Xultophy, the fixed combination of (Tresiba) and Victoza (liraglutide). Xultophy was launched in the UK in June 2015 and will be rolled out in more countries during the year.

Dr Klaus Henning Jensen, medical director at Novo Nordisk UK, told Pharmafocus: “We take a very sequential view at Novo Nordisk with several drugs in our regulatory pipeline: namely Xultophy in 2015 and Saxenda for obesity in 2016.Our focus right now is Xultophy. We have extremely busy preparing for our launch, which is being rolled out in different countries within the next six to 12 months.

“We believe that Xultophy provides some clear benefits for a clear group of patients with type 2 diabetes who are not sufficiently well controlled on basal insulins. But what’s probably most important to patients and doctors is that it’s available as one single pen. When it comes to prescribing I believe we are differentiated in its efficacy. This product it’s not just a different strategy. We were following the clinical science but not just offering a convenience benefit.”

Growing patient need

In the UK, it’s estimated that there are currently 3.3 million people in the UK diagnosed with diabetes – up from up from 2.1 million in 2005, a rise of 60%. And this figure is predicted to rise to five million people by 2025, as is the cost of treatment. Figures from the NHS Health and Social Care Information Centre (HSCIC) show that in 2014/15 the net ingredient cost (NIC) of drugs for managing diabetes was £868.6 million. The figures represent 10% of the total £8.71 billion primary care prescribing spend in 2014/15, a rise from 9.5% in 2013/14 and 6.6% in 2005/06.

Recent figures from the charity Diabetes UK paints an even starker picture. They estimate that there are 3.8 million people in the UK living with diabetes, and the most comprehensive analysis to date concludes that the cost of diabetes to the NHS is £9.8bn in direct costs in 2010/11 with £1bn for type 1 and £8.8bn for type 2. A report by Public Health England says another five million people are at risk of the condition.

So the pressure on the NHS is intense, and in the prevailing NHS climate, costs that go up must come down, in order to meet tough targets on efficiency savings right across the health service. Many within the health service are looking to a new generation of copycat, biosimilar versions of insulins to provide significant cost savings for these drugs.

Growth of biosimilar market

Biosimilar medicines are structurally complex compounds that are similar, but not identical, to an already approved biologic medicine (known as the reference medicine). Biosimilars are not the same as generics. Generic medicines are exact copies of small compounds produced by chemical synthesis, whilst biosimilar medicines are similar versions of large, structurally complex compounds made by genetically modified living cells. However biosimilars are designed to have no clinically meaningful difference – including crucially for patients, in efficacy and safety – compared to their reference medicine.

As a reflection of this difference, it is worth noting that the cost of developing biosimilars is very different to generics. According to IMS Health, the typical cost of developing a new generic is $1-4 million, whereas developing a biosimilar will cost between $100 and $250 million. In practice this means price differences for biosimilars are unlikely to reach the same level of price difference as seen between branded medicines and generics. However the savings are still expected to be in the order of 20-30% of insulins and other biological drugs.

Several pharma companies are lining up with biosimilar versions of insulin products, to make inroads into the established insulin market. Lilly and Boehringer Ingelheim already have a biosmiliar insulin product looking to challenge the traditional dominance of the market, which has been led by Novo Nordisk and the alliance’s direct competitor, Sanofi.

Their insulin glargine product, abasalgar, was licensed by the European Commission in September 2014 for the treatment of diabetes in adults, adolescents, and children aged 2 years and older. The copycat version of Sanofi’s best-selling insulin, Lantus, is the fourth diabetes product approved in the EU under a Lilly-Boehringer alliance, and will be made available in a pre-filled pen along with cartridges.

Lantus is Sanofi’s biggest-selling product, generating sales in 2014 of around $8.43 billion. Abasaglar launched in the UK in August after a bitter patent infringement lawsuit between Sanofi and Lilly in 2014, that abasaglar was blocked from being commercialised in the EU until the Lantus patent expired.

A Lilly spokeswoman says: “The introduction of biosimilars can help expand the range of available treatment options that health care professionals can prescribe. We are aware of the expectation by over-stretched health systems, such as the NHS, for biosimilars to offer a cost-efficiency versus the original reference molecule.

“The first priority for healthcare companies today is to match the medicine to the specific need in a patient’s treatment journey and we believe that payer policies should allow the healthcare professional the freedom to choose either the current medicine or biosimilar product.   

Merck also has an insulin biosimilar in development, MK-1293, and has completed a head-to-head Phase III study comparing MK-1293 with Sanofi’s Lantus in people with type 2 diabetes. It is also being weighed against Lantus and Novo Nordisk’s Novolog in a Phase I patients with type 1 diabetes.

In response to the threat from biosimilars Sanofi has looked to develop products as the successors to Lantus. The French firm has launched Toujeo, its new insulin glargine product, in the UK, and it is already available in the US, Canada, the European Union and Japan.

Controversial guidelines

In the UK, research shows that more than two-thirds of adults with diabetes who take insulin do not meet the NICE target for blood glucose control, which raises their risk of potentially avoidable complications including amputation, blindness and renal disease.

In a bid to improve this, NICE published new guidelines in August encouraging healthcare professionals to aim for tighter blood sugar control to improve the management of diabetes in children and adults.  The three NICE guidelines cover type 1 diabetes in adults, type 1 and 2 diabetes in children and young people and diabetic foot problems.

These are guidelines are much less controversial than the ongoing review of the NICE guidelines on type 2 diabetes in adults. The draft version of the guideline has been heavily criticised by pharma companies and clinicians, who warned NICE initial decision to recommend repaglinide – a drug experts point out has not been widely used since its launch in the 1990s – as an alternative first-line therapy in people who cannot tolerate metformin, risked setting back diabetes care by ignoring newer treatment options.

Novo Nordisk provided input on the guidelines – due for publication in October – along with other companies and stakeholders, Henning Jensen says. “The NICE guidelines are going to be a big area of discussion. I think it’s important that they are scrutinised. I think it’s favourable that there is a focus on patient education but there’s some concern about the heavy focus on some of the more traditional treatments.”

The guidelines for type 1 diabetes in adults, type 1 and 2 diabetes in children and young people and diabetic foot problems, Sir Andrew Dillon, NICE chief executive, says: “The standard of diabetes care varies across the NHS. These updated guidelines recommend effective and cost effective care and advice to NHS organisations on such things as setting up specialist services to reduce risk of diabetes-related amputation.” It focusses on structured education programmes, a target HbA1c level of 48 mmol/mol (6.5%) or lower, and multiple daily injection of basal–bolus insulin regimens, ta maintain blood sugar control.

Type 1 challenge

Companies are also looking to the type 1 diabetes market, and here NICE guidance on managing the condition in children and young adults – in whom the condition is much more common. In the UK Type 1 diabetes affects more than 370,000 adults, and 25 in 100,000 children aged under 14 are diagnosed with type 1 diabetes every year, which is double the rate in France and Italy.

Insulin therapy is the mainstay of type 1 diabetes treatment, and globally the type 1 diabetes market is set to expand from $6.6 billion in 2013 to an estimated $13.6 billion by 2023 – a compound annual growth rate of 7.6% – according to research and consulting firm GlobalData.

Across the eight major markets of the US, France, Germany, Italy, Spain, UK, Japan, and Canada, growth will be driven primarily by increasing type 1 diabetes incidence and the substantially higher annual cost of therapy in the US.

Valentina Gburcik, GlobalData’s therapy director of cardiovascular and metabolic disorders, says: “The uptake of novel ultra-long-acting insulin analogs, novel ultra-rapid formulations of insulin analogs, and adjunct therapies for type 1 diabetes, in the US market will help to offset the dip in sales caused by the patent expiries of seven insulin products by 2023.”

GlobalData’s report also states that human insulins and insulin analogs will remain front-line therapies for type 1 diabetes, as none of the treatments on the horizon for the next 10 years will have the capacity to enable full regeneration of pancreatic beta cells.

However, Gburcik notes that therapies currently used for type 2 diabetes, namely GLP-1 receptor angonists and sodium- glucose cotransporter 2 (SGLT-2) inhibitors, are expected to be approved for type 1 diabetes from around 2017.

In the UK they are being assessed by NICE, with guidelines on canagliflozin (Janssen’s Invokana), BMS and AstraZeneca’s Farxiga (dapagliflozin) and Boehringer Ingelheim’s Jardiance (empagliflozin) due in May 2016. GlobalData predicts these drugs will have a considerable impact on the global type 1 diabetes market by 2023, constituting 9% and 11% of the arena, respectively.

“These therapies will not compete with the insulins, as they will be prescribed as adjunct, add-on treatments. They will be used particularly in obese type 1 diabetes patients and those with a mixed type 1 and type 2 phenotype,” Gburcik says.

Pharma companies can help reduce the cost of diabetes, with better drugs for diabetes, and complications including high blood pressure, end-stage kidney disease and high cholesterol for people with a history of cardio-vascular disease. However, unlike many other cost-saving interventions, it seems that these are mostly already being used effectively and so there is only limited scope for improvement.

The cost pressures facing the NHS will not go away in a couple of years and expenditure on diabetes is rising. It is only by acting now to get the care right that we will reduce the rate of complications and so ease the cost pressure on the NHS. But too often, the opposite is happening, with short-term budget cuts being made that will inevitably store up huge costs – in terms of both money and patient cost – for the future.

Now and then: the top five best-selling diabetes drugs in 2014 and 2020

Source: Company financial results

Source: Bloomberg

Future Innovations: The promise of stem cells in diabetes

Stem cells have the ability to develop into many different cell types, which means they have great therapeutic potential. Cells found in the early embryo can give rise to pluripotent embryonic stem cell cultures that maintain the ability to mature into any cell type – including insulin-producing beta cells – while stem cells in the adult body can normally only mature into a limited number of specialised cells. As it has not yet been demonstrated that the same scientific results can be obtained using adult stem cells, companies are using human embryonic stem cells in order to progress the company’s research into developing beta cells for potential transplantation into patients as a cure for diabetes.