Janssen has submitted a Marketing Authorisation Application to the EMA for the approval of a fixed-dose therapy which would combine canagliflozin and immediate release metformin for the treatment of type 2 diabetes.

Canagliflozin is an investigational, oral medication for adult patients which blocks the reabsorption of glucose by the kidney, increasing glucose excretion and lowering blood glucose levels.

Metformin is a first-line pharmacotherapy which is used either alone or in combination with other medications, including insulin, to treat type 2 diabetes.

When combined, the fixed-dose therapy may offer adult patients a convenient medication in a single pill.

Janssen submitted a similar application to the US FDA for canagliflozin on 31 May 2012 and for a fixed-dose therapy combining canagliflozin and immediate release metformin on 12 December 2012.

Rosemont Pharmaceuticals, the leading UK supplier of liquid oral medicines, has been acquired by US company Perrigo.

The merger will enable Perrigo, a major supplier of over the counter (OTC) products, to add a range of liquid-form drugs to its generic prescription drugs portfolio.

Leeds-based firm Rosemont, sold for £180m, has seen its business grow dramatically in recent years due to the ageing population.

Its liquid formulation versions of widely-prescribed drugs such as metformin target paediatric patients and people suffering from dysphagia (which affects many elderly patients), with net sales of £40m in 2012.

Perrigo will benefit from the UK firm’s niche market, an area of critical medical need with demographic factors driving an increase in its size; and from the opportunity to expand its range of generic prescription medicines in the UK and Europe.

Joseph C. Papa, CEO of Perrigo, said: “We continue to focus on expanding our international footprint and view the acquisition of Rosemont as an opportunistic next step given our existing presence in the UK.

“Similar to Perrigo’s position in the niche US extended topical generic prescription market, Rosemont is the number 1 player in the niche specialty UK oral liquid formulations market.

“This transaction represents another step forward executing our strategy to make quality healthcare products more affordable for consumers around the world.”

Based in Michigan, Perrigo is the world’s largest manufacturer of OTC pharmaceuticals for the store brand market, as well a major supplier of generic prescription drugs.

NICE has requested further information on Forxiga (dapagliflozin) as a combination therapy option to treat type 2 diabetes after failing to recommend the product in draft guidance.

Bristol-Myers Squibb and AstraZeneca have been asked for further clarification and information after concerns were raised about trial data and the cost modelling of the drug.

Forxiga has a UK marketing authorisation in adults with type 2 diabetes mellitus. It’s used as monotherapy when diet and exercise alone do not provide adequate control and as an add-on combination therapy with other treatments, such as insulin and metformin.

During the appraisal, NICE’s independent Appraisal Committee questioned the evidence on the clinical effectiveness of Forxiga as an add-on to insulin and metformin.

The Committee noted that the trial data for the drug as an add-on therapy to insulin came from two placebo-controlled trials – one of which was only 12 weeks in duration. The evidence supplied for Forxiga as an add-on to metformin came from three clinical trials and a network meta-analysis.

Concerns were also raised by the Committee surrounding the comparisons made by BMS and AZ of the cost of Forxiga and with that of other anti-diabetic drug therapies and how these were initially made.

“Type 2 diabetes is a serious problem in the UK and it is important that there is a range of different treatment options available,” said Professor Carole Longson, Health Technology Evaluation Centre Director at NICE. “Unfortunately the Appraisal Committee is currently unable to recommend dapagliflozin, one of the options, for the treatment of this condition. They have requested further information from the manufacturer, which will be considered at the next Appraisal Committee meeting in April.”

Final guidance is expected in June 2013.

As the incidence of diabetes in the UK soars, the austerity NHS is increasingly unable to meet the needs of patients with this complex and lethal disease. How can the pharmaceutical industry help the situation?

Blindness. Foot and leg amputation. Kidney failure. These are among the complications of diabetes, a complex metabolic disorder that is now the leading health challenge facing western society.
In diabetes the absorption of glucose (sugar) from the blood fails, causing it to accumulate in the circulatory system. This occurs either because the pancreas stops producing the hormone insulin (type 1 diabetes) or because insulin production is inadequate or the body’s response to it is poor (type 2 diabetes).
Both types of diabetes have genetic risk factors, but type 2 or ‘mature onset’ diabetes has other risk factors such as age, obesity and lack of exercise. Type 1 or ‘juvenile onset’ diabetes is fatal unless the missing insulin is replaced by injection. In type 2 diabetes, a range of medications such as metformin can be used to improve glucose uptake.

The number of people diagnosed with diabetes in the UK has increased from 1.4 million in 1996 to 2.9 million in 2012, and continues to rise, with type 1 diabetes now accounting for only 10% of the total. The prevalence of type 2 diabetes has risen sharply, due to the ageing population and the trend towards obesity.

There is no cure for diabetes. A range of medications exist to treat it, but establishing the correct dosage levels is not easy: only an estimated 6% of diabetes patients get the balance right. Since no medication can make diabetes go away, the condition demands constant monitoring and medication adjustment, as well as checks for complications.

And at a time of deepening austerity in NHS funding, that level of attention to patient needs is getting harder to afford. All the signs are that people with diabetes (especially the more high-maintenance type 1) in the UK are at increasing risk of disabling or fatal complications. Sugar is killing more of us all the time.

High and dry
In November 2012, the Public Accounts Committee observed that diabetes care in England was “depressingly poor”, with 24,000 preventable deaths from the disease happening each year. The report pointed to a lack of clinical leadership and a ‘postcode lottery’ in diabetes care.

Barabara Young, Chief Executive of charity Diabetes UK, commented: “Given all the increasingly strong evidence of inadequate care, we simply cannot understand why the NHS has sleepwalked into this situation.”

During 2012, Diabetes UK drew attention to the need for better access to diagnostics, more referrals to specialist care, and wider awareness of the role of healthy lifestyle in preventing and controlling diabetes.
In April 2012, Young noted that 80% of NHS spending on diabetes care went on treating preventable complications. In May 2012, Diabetes UK stated that diabetes care in England was in a “state of crisis” with fewer than half of patients receiving adequate care.

Yet the medicines and diagnostics exist to reduce the incidence of diabetes, manage the condition and avoid complications. It’s not rocket science. What has gone wrong – and what is the solution?

A preventable crisis
Tracy Kelly, Head of Care at Diabetes UK, spoke to Pf about the problems of diabetes care. For the patient, she said, “Optimal diabetes control requires dedication and motivation from the individual to test, inject or take medication, adjust their dietary intake, potentially make lifestyle changes, monitor their condition and ensure they are receiving their health checks.”

This puts the patient under intense pressure, especially if they have other chronic conditions. How can the pharmaceutical industry help? In three ways, Kelly said: “Better provision of information and education for people with diabetes and for the healthcare professionals; commitment to research into new and improved treatments and monitoring approaches; and bridging the gap in healthcare services by supporting specialist nurses and dieticians in hospitals, for example with pump training and starting on insulin.”
Importantly, Kelly noted, the agendas of drug treatment and lifestyle change are not opposed: “There should always be a dual approach.” In treating both types of diabetes, clinicians need to look for the optimum blend of medication and lifestyle factors for each patient. The NHS needs to deliver programmes of risk assessment and early diagnosis; offer effective education in self-care for all patients; and ensure that they receive the nine regular checks recommended by NICE.

Working together
Successful diabetes care depends on integrating primary and specialist care, Kelly emphasised. “Effective diabetes care can only be achieved through integration. There must be clear referral plans in place and transparency about who does what and where specialist diabetes care is required. Specialist teams also have a key role to play in educating and supporting primary care.”

Cutting down on GP referrals is a growing NHS trend, praised by David Nicholson in his 2012 NHS review and promised in many CCG commissioning plans. Does this pose a threat to diabetes care? Kelly’s response was clear: “Cutting down referrals to specialist care may increase the risk of complications and could result in increasing costs to the health system. Diabetes is complex and any blanket rules to cut referrals could put lives at risk over the long term.”

For patients with type 1 diabetes, in particular, referral management is a recipe for trouble: “We know it is important for people with type 1 to have access to a team of specialists such as a dietician, podiatrist and counsellor. But often their access to this kind of support only comes once complications have developed.”
In short, drug manufacturers and healthcare providers can work together to support patients in avoiding complications – but clumsy cost-driven applications of QIPP are tending to disable care.

The hidden disease
As Louis MacNeice said, the North begins inside. Danish pharmaceutical company Novo Nordisk has specialised in diabetes care since its launch in 1923. Its insulin products (used by many type 2 as well as type 1 patients) are the standard of care in the UK. The company’s CEO, Lars Sorensen, recently observed: “What we are good at, all of a sudden becomes the biggest public health problem we have ever seen.”
Peter Meeus, Vice President, Novo Nordisk UK and Ireland, spoke to Pf about the company’s role in meeting the diabetes challenge. He noted that according to the National Diabetes Audit, only half of diagnosed patients in the UK are achieving treatment targets, while fewer than half of all people with diabetes receive all nine recommended healthcare checks.

Too often, Meeus noted, diabetes is only detected when secondary complications arise such as retinopathy and foot ulcers. Insulin can be the most effective treatment, but fear of injecting is sometimes a barrier to its adoption. As a result, “many patients start on insulin too late and are therefore at risk for developing serious late complications”. This is unfortunate, as the needles used today are much thinner and less painful.

Shot in the dark
According to Meeus, the pharmaceutical industry can help the NHS meet the challenge of diabetes by helping to identify the high proportion of diabetes patients who are poorly controlled, and to ensure these patients achieve control within the national guidelines.

He added: “Novo Nordisk is working with the DH and local health economies, together with physicians, to deliver agreed diabetes health outcomes at both national and local level, using appropriate innovative medicinal interventions as well as service design and support.” Specifically, the company provides Diabetes Education Nurse Facilitators to primary and secondary care organisations where needed, and its local Diabetes Outcomes Directors work to assist the redesign of diabetes services.

The company may owe its current growth in part to the growing incidence of diabetes, Meeus said, but its depth of experience in this therapy area has enabled it to take advantage of the opportunities: “Innovation and science have always been at the core of Novo Nordisk’s business, and as a result we today have the broadest portfolio of R&D diabetes projects. At a time when others in the pharmaceutical industry are cutting R&D budgets, we’re increasing our investment.”

“The challenge going forward,” he concluded, “is the fact that diabetes today is the biggest problem for healthcare systems, but at the same time the healthcare budgets are under increased pressure.” Diabetes UK and millions of patients would agree. But where there’s a will, there’s (sometimes) a way.

Everyone in pharma is talking about key account management – but what does being a KAM mean for the sales executive?

What is key account management all about? Perhaps an anecdote will help...

A travelling salesman was on the road and stopped in a small Somerset town. There appeared to be no hotel and the local pub had no rooms available. So he drove out to the nearest farm and knocked on the door. An ageing man answered. The rep explained his problem and asked if the farmer had any rooms available. “Sure,” the old man said. “My 19-year-old daughter normally lives here but she’s away at college, so her room’s free.” The rep nodded and turned back to his car. “Hang on,” the farmer said. “I said there’s a free room.” “I’m sorry,” said the rep, “I’m in the wrong joke.”

The point is that a traditional sales rep has a well-defined script, a known role, within which certain messages and behaviours are taken for granted. The rep just has to make contact and deliver the message. That’s why he or she is the butt of so many jokes. It’s also why the traditional sales role is disappearing from our information-charged world of informed customers and organisations that make decisions on a committee basis.

Read the joke again and think of it as a metaphor for a modern business relationship.  The farmer’s spare room stands for the technological and human resources the customer can draw on. The farmer’s daughter being in college stands for the customer’s new education and range of business contacts.

To employ a technical metaphor, if the traditional sales executive is a plug looking for a socket, the key account manager is a USB flash drive from which a wealth of complex information can be downloaded. The KAM is not only addressing a plurality of customers but representing a plurality of company perspectives: sales, marketing, research, finance and management.

You’ve heard of cloud computing. Key account management is cloud selling – a way of bringing together the best elements of your company’s business strategy with the key aspects of the customer organisation’s business strategy. That classic business cliché, my people will talk to your people, is at the heart of KAM.

Meeting the family
Key account management assumes that the individual customer belongs to a complex buying environment – he/she is influenced by a range of people and uses a range of information resources. The appropriateness of this model to the NHS is obvious – and while the current NHS reforms affect the structure and workings of key healthcare accounts, they certainly do not dilute the need for such accounts. The KAM has to work with the purchasing system by identifying, and building relationships with, its most sensitive points of contact.

Identifying the decision making units within the customer organisation and working strategically to maximise your company’s impact on them is half of the battle. The other half is directly or indirectly bringing the key elements of your own company into contact with the customer organisation. This is where new technology comes into its own: nothing will make connections better than well-presented information that conveys the richness and immediacy of your business case. Tablet computers and smartphones also make the co-ordination of KAM within your own company swifter and easier.

As many pharma companies have found out, simply creating a KAM role in your sales team and expecting that to make all the difference is foolish. KAM is a function of the whole company – which seeks to meet the needs of patients via the health systems that provide treatment. The product reaches the patient via a treatment pathway that the health system develops according to its clinical and financial priorities. That pathway and the reasons for it are what the company needs to understand and change.

Looking after people
Pf spoke with Paul Curbbun, National Key Account Manager at Rosemont Pharmaceuticals. Before taking on his current role, Paul was National Hospital Manager for the same company. Before that, he was working in FMCG and other sales sectors – where KAM has been prevalent for two decades. So Paul is the KAM who came in from the cold.

On how his working life has changed, Paul says: “My life hasn’t got any easier or any harder. The only thing I’ve cut down slightly is the mileage. I’m at home more than before because I tend to use home as my office. For instance, this morning I’m spending two or three hours at home preparing before going out. There’s a lot more reports to put together as well as analysis of sales.”

On the changes in his customer base, he observes: “As NHM, I was seeing everybody – pharmacists, nurses, doctors, therapists. That’s all gone now, and what I’m seeing is mainly the buyers from the key groups, from specific retail groups to wholesalers. A lot of what I’m doing is building up business partners.”

What KAM is all about, he argues, is looking after customers: “Nothing feels better than when you’ve asked for something and you get that something. It’s about not letting people down. It’s truly looking at their business and your business and linking the two together for the benefit of both.”

That contrasts with the traditional pharmaceutical sales role of hammering the product and the marketing message. The key account manager needs to identify opportunities and develop solutions, using the company’s product portfolio to optimal effect. “Whatever the account needs – it’s that simple.”

Don’t be a stranger
Rosemont Pharmaceuticals specialises in oral liquid medicines for people who have difficulty with tablets. Their products include a formulation of the diabetes drug metformin. With a clear USP and well-defined patient population, surely this is a case for traditional product-based selling? By no means, says Paul: “It’s critical that when a patient needs an alternative, a patient gets an alternative. So from a key account point of view, you can make sure our products are where they need to be, so that patients get the right medicine and, most importantly, there is continuity of supply.”

For the sales professional, Paul states, the difference between KAM and their previous approach depends on how well they did the latter. “If you’re making calls for the sake of it, just to tick a box, obviously that’s a long way off – but if you’re going into an account with complete business focus, asking what it needs, closing the loop whenever an opportunity arises, you’re well on the way to a KAM role.” Sales professionals who analyse their sales and construct a business-focused customer database are also showing KAM awareness.

For the sales manager, the key to effective KAM is empowering the sales team to manage and take ownership of their accounts while guiding them to optimise their work as a team. KAM is not a solo activity. Paul remarks with some bafflement: “Something I could never get my head around was the fact that you often had four or five people selling the same drug over the same area. If you were devising a business model tomorrow, that would certainly not be it.”

In fact, KAM is so integral to modern business that it’s worth asking why the pharmaceutical industry avoided it for so long. The answer lies in its assumption of a difference in professionalism and consciousness between seller and buyer. For decades, pharma regarded its customers as business-naive people fixated on the patient relationship. Hence the adoption of ‘persuasion’ techniques such as NLP.

Times have changed, and bad business habits now carry too high a price. As the NHS – with its emphasis on cost-effectiveness and generic prescribing – becomes more like a business, and the industry – with its emphasis on patient-centred medicine and disease area knowledge – becomes more like a doctor, a shift from sales transactions to commercial relationships is essential for both. KAM is pharma’s only way in from the cold.

A new convenient tablet for the treatment of type 2 diabetes has been launched in the UK.

Boehringer Ingelheim/Eli Lilly’s Jentadueto was licensed in Europe in July earlier this year after Phase III data showed it led to a significant reduction in HbA1c glucose levels.

Jentadueto combines metformin with the dipeptidyl peptidase (DPP)-IV inhibitor Trajenta (linagliptin) in a single pill.

Dr Richard Brice, Chair of Whitstable Medical Practice, said the new treatment provides patients with a convenient alternative to existing options. “Compliance is a recurring problem for patients, especially those with comorbidities such as hypertension, dyslipidaemia, cardiovascular disease and depression, struggling to take a number of tablets every day,” he said.

The prevalence of diabetes is expected to increase rapidly in the UK in coming years – placing further pressure on healthcare services. By 2030, it’s expected that more than 5.5 million people in the UK will have diabetes.

New NICE guidance recommends ‘stepped’ risk assessments for type 2 diabetes and early intervention in cases of high risk.

Risk assessments are recommended for adults aged over 40; adults aged over 25 in certain ethnic groups; and adults with conditions that increase the risk of diabetes.

Individuals at high risk should be offered a blood test and treated through an intensive lifestyle change programme that may include medication.

Diabetes affects an estimated three million people in the UK – predicted to rise to five million by 2025 – and type 2 diabetes accounts for 90% of the total.

NICE observes that individual risk of developing type 2 diabetes can be reduced by 60% through lifestyle changes including diet and exercise.

The new guidance recommends that risk assessments be offered to people (except pregnant women) in the following groups:

• adults aged 40 or over

• adults aged 25 or over who are of South Asian, Chinese, African-Caribbean or Black African origin

• adults with conditions that increase the risk of type 2 diabetes, including obesity, hypertension and mental illness.

Individuals considered at high risk should be offered a blood test (fasting glucose or HbA1c) at least once a year, and the correct level of intervention decided accordingly.

NICE recommends preventative measures such as diet and exercise regimes. Medications such as metformin (to improve insulin uptake) and orlistat (to assist weight loss) may be used to treat ‘pre-diabetes’.

As well as helping to prevent type 2 diabetes, these measures will help to diagnose the condition – it is estimated that 850,000 people in the UK have undiagnosed diabetes.

“We are not just seeing an epidemic of type 2 diabetes, it is a tsunami,” said Professor Kamlesh Khunti, chair of the NICE guidance development group.

Patients taking both metformin and insulin to help control their type 2 diabetes instead of insulin alone may not benefit from dual therapy, a new study claims.

Researchers from the Copenhagen Trial Unit, Steno Hospital, and the Copenhagen University Hospital agree the combination has a number of positive aspects but questioned the long term benefits for patients.

Authors of the study, published on bmj.com, say that more trials are necessary to provide firm evidence about the effectiveness of the combination, its long term risks and, in particular the risk of premature death.

The study included 2,217 patients over the age of 18 who had type 2 diabetes. It found various examples where levels of HbA1c were reduced with the combination of an oral glucose lowering drug and insulin.

Also, BMI levels and weight gain were also significantly reduced by metformin plus insulin by an average of 1.6kg.

However, a sparse number of important patient outcomes, including mortality from cardiovascular disease and other causes, have led the study’s authors to call for further research on long term risks.

Metformin is currently recommended by guidelines for patients with type 2 diabetes starting on insulin.

Leading diabetes drug metformin may have potential indications as a treatment for several types of cancer, including cancer of the prostate, liver and pancreas.

New studies have shown that metformin may slow down the growth of prostate cancer, prolong life expectancy in patients with early-stage pancreatic cancer, and help to prevent liver cancer.

If metformin is confirmed as an effective cancer therapy, it could help to reduce both the costs and the side-effects of cancer treatment.

Researchers have pointed to “strong signals of an anti-cancer effect” with metformin, but emphasised that further clinical studies are needed.

A Canadian study in 22 adult males with prostate cancer showed that high doses of metformin, given for an average of 41 days, slowed tumour growth by 32%.

Reasons for this effect could include direct impact on cancer cell metabolism and reduced bloodstream levels of insulin, which enhances tumour growth.

Nancy Dawson, prostate cancer specialist at a Georgetown cancer centre, commented: “It’s very early and the study is small. But it’s fascinating to see such a slowing of cancer cell growth in such a short period of time.”

A Texan study examined data on 302 people with pancreatic cancer and diabetes, of whom 117 took metformin. It found that 30% of those taking metformin were alive after two years, compared to 15% of those not taking it. The average survival was 15 months with metformin and 11 months without.

A Maryland study in mice showed that metformin was significantly effective in preventing primary liver cancer – a disease for which type 2 diabetes, obesity and hepatitis are risk factors in humans. Mice given metformin showed 57% fewer liver tumours, and their average tumour size was 37% smaller.

Study author Geoffrey D. Girnun said: “Based on these findings, we believe metformin should be evaluated as a preventive agent in people who are at high risk.”

Further studies are planned, but there is strong interest in the cancer-treating potential of this successful diabetes drug.

“These are still the early days,” noted Jose Baselga, Chief of Oncology at Massachusetts General Hospital. “But there are strong signals of an anti-cancer effect.”

The European Commission has granted marketing authorisation to Byetta (exenatide twice-daily) as an adjunctive therapy to basal insulin in adults with type 2 diabetes who have not achieved adequate glycaemic control.

The authorisation for adults who have not responded to metformin and/or Actos follows clinical trial data which showed Byetta helped reduced glucose levels and reduce patients’ weight.

Dr Christian Weyer, Senior Vice President, R&D, Amylin Pharmaceuticals, said the decision “provides a new option” for patients who are not “achieving treatment goals”.

Byetta, the first glucagon-like peptide-1 (GLP-1) receptor agonist to be approved by the FDA for the treatment of type 2 diabetes, has been used by more than 1.8 million patients globally since its introduction.

In the main, double-blind, 30-week clinical trials, submitted to the EC, Byetta demonstrated a statistically significant reduction of hypoglycaemia compared to placebo. Participants who added Byetta to their insulin glargine regimen also saw their weight decrease by an average of four pounds.

“In a clinical trial, patients using fixed-dose Byetta with titrated basal insulin achieved better postprandial and overall glycaemic control, without weight gain or an increased risk of hypoglycaemia, compared to patients using titrated basal insulin without Byetta,” said Dr Weyer.