The ‘metabolic’ health of younger adults is worse than that of previous generations, exposing them to greater risks of cardiovascular disease.

A large cohort study from the Netherlands found the incidence of obesity, high blood pressure and high cholesterol were much higher among adults in their twenties and thirties than formerly.

This increase in risk factors for diabetes, stroke and heart disease could offset the advantage of reduced incidence of lung cancer from the decline in smoking.

The researchers analysed data on more than 6,000 individuals in a cohort study that began in 1987, with follow-up examinations after six, 11 and 16 years, measuring body weight, blood pressure and total cholesterol level.

The subjects were divided into ten-year age groups to help determine whether there were ‘generation shifts’ in risk profile.

The results showed that while the prevalence of obesity and hypertension increased with age, the younger generations had a higher prevalence of these risk factors than those 10 years had shown at the same age. For example:

• incidence of overweight among men in their thirties had increased over 11 years from 40% to 52%

• incidence of hypertension had increased between generations in both sexes

• incidence of diabetes had increased between generations in men.

The investigators concluded that “the more recently born adult generations are doing worse than their predecessors”.

Lead study author Gerben Hulsegge commented that in terms of the prevalence of obesity, the younger generation was “15 years ahead” of the older.

He predicted: “We are likely to see a shift in non-communicable disease from smoking-related diseases such as lung cancer to obesity-related diseases such as diabetes.” As a result, he warned, increases in life expectancy could level off.

The global market in statins, once the pharmaceutical industry’s lead blockbuster products, is predicted to decline by 40% in the next five years.

The forecast by GBI Research of a negative CAGR of 7.2% up to 2013 for the cholesterol-lowering drugs is based on prospects of generic erosion, weak pipelines and failing prescriber confidence.

The decline in the statins market shows that the shift of healthcare towards prevention and management of long-term conditions is not without pitfalls for the pharma industry.

Statins, which lower cholesterol levels by targeting an enzyme in the liver, have been hailed as ‘wonder drugs’ that could radically reduce the global incidence of cardiovascular events.

Routinely prescribed for ‘high-risk’ patients such as people with high blood pressure or diabetes, statins have also been linked to reduced risk of bowel cancer and reduced death rate from influenza.

However, their global market declined from $23.7 billion in 2004 to $20.5 billion in 2011 (a negative CAGR of 2.5%), due largely to patent expiry.

The report predicts a much steeper decline in the statins market over the next five years, for four reasons:

• Patent expiry – the generic share of the statins market is predicted to grow from 11% in 2011 to 34% in 2018.

• Austerity health budgets – spending on prevention is likely to be cut back.

• Weak product pipelines – the ‘me-too’ nature of most statins betrays a lack of potential for innovation.

• Increased use of alternative drugs.

Medical writer Ben Goldacre has argued that the marketing of statins in terms of relative risk reduction glossed over the low absolute risk reduction they offer, and left the products open to a backlash over side-effects.

Statins are associated with both symptomatic side-effects (including digestive disorders) and potential ones (including increased risk of type 2 diabetes).

As the overall statins market declines, the report says, individual products will struggle to gain or keep a place within it: “The global statins market has reached the competitive stage of its lifecycle, with many branded and generic drugs competing with each other on price.”

Different statins vary in their potential to cause diabetes as a side-effect in certain patients, new research has shown.

Evidence presented at the World Congress on Prevention of Diabetes and its Complications (WCPD) in Madrid suggests that pitavastatin and pravastatin may pose less risk than other statins.

The Congress also noted that concern over diabetes risk has affected worldwide prescribing of statins in general.

Despite being the most-prescribed type of drug, statins – which have been shown to reduce blood cholesterol levels and this risk of cardiovascular events – have a range of medically significant side-effects.

Most notably, a meta-analysis of 13 trials with 91,000 participants has found that statin use is associated with 9% increase in risk of new-onset diabetes.

More recent studies suggest this effect varies strongly between drugs in the statin class, with atorvastatin increasing long-range blood glucose in intensive doses but with pitavastatin and pravastatin having no such impact.

The new J-PREDICT trial in Japan, due to conclude in 2015, is testing the effect of pitavastatin on risk of diabetes in 1,200 people with ‘pre-diabetes’ (impaired glucose tolerance).

Pitavastatin, the lead product of Japanese company Kowa, will be marketed (as Livazo) by Recordati in Europe, where it received MHRA approval in 2010.

Prof. Kausik Ray, Professor of Cardiovascular Disease Prevention at St George’s, University of London, said: “These insights demonstrate how the medical community is taking the diabetogenic risk of statins seriously and highlight the need for further research and guidance in how to treat patients with high cholesterol who are at risk of developing diabetes.”

The new NHS Mandate, presented to Parliament by Health Secretary Jeremy Hunt, has replaced the draft version’s outcome targets with requirements for “measurable progress”.

The final Mandate, which establishes the strategic objectives for the NHS Commissioning Board (NHS CB), maintains the broad goals of the draft version but is lighter on specific commitments.

Positive responses from the NHS CB and the BMA suggest that criticisms of the draft version as being over-prescriptive have been addressed.

Significant changes include the loss of definite overarching commitments to reduce premature death and increase quality of life for the chronically ill.

More generally, where quantitative outcome targets were set with the numbers pending consultation, there is now only a requirement to improve.

The Mandate states that improvements should be measurable by March 2015, the end of the Board’s first term of office.

As before, it notes the duty of the Board and the DH to promote “the autonomy of local clinical commissioners”, and identifies this is the means by which outcomes will be improved.

Key priorities for improvement include: standards of treatment for older patients; diagnosis, treatment and care of people with dementia; support for people with multiple physical and mental long-term conditions; and preventing premature deaths from major diseases.

The section on premature deaths notes the importance of “tackling risk factors such as high blood pressure and cholesterol”, as well as ensuring that patients have access to NICE-approved drugs.

The section on long-term conditions places emphasis on integration of care and on patient choice. Personalised care plans and personal health budgets are promised, as well as online access for patients to their care records and the means to book appointments and repeat prescriptions.

Dementia is highlighted as a priority, with progress towards “timely diagnosis and the best available treatment” set as an objective. A further aim is “to put mental health on a par with physical health” and address poor access to healthcare among the mentally ill.

A section on innovation repeats the previous commitment to introducing the controversial “quality premium” for GPs, as well as establishing a “fair playing field” for competing providers from all sectors.

The Mandate stresses the need for “redesigning services, open procurement and contracting for outcomes” – which reaffirms the Government’s commitment to the NHS innovation agenda as well as the role of the private sector.

Sir David Nicholson, Chief Executive of the NHS CB, commented: “The Mandate avoids the danger of excessively prescribing the actions of health professionals. Our role will be to work closely with local clinical leaders and provide the support they need. Our role is not to tell them what to do.”

Dr Mark Porter, Chair of BMA Council, praised the “welcome reduction in targets, objectives and micromanaging” from the draft Mandate, but noted: “If the NHSCB’s strategic vision is to be delivered, ministers must ensure there is genuine clinical involvement and adequate resourcing.”

Commenting on the Government’s innovation agenda, ABPI Chief Executive Stephen Whitehead said: “The NHS Mandate must work hand-in-hand with Innovation, Health and Wealth to help break down barriers to innovation in the NHS and to ensure that new medicines reach patients.”

Teva has cancelled its plans to join the already crowded market for atorvastatin, the generic version of Pfizer’s fading blockbuster Lipitor.

The global generics leader will collaborate with Indian companies Ranbaxy and Dr. Reddy’s to promote the cholesterol-lowering drug in the US market, without offering its own version.

The decision, according to Teva, came down to two factors: increasing competition and limited manufacturing capability.

Since Lipitor’s patent expiry in November 2011 (US) and May 2012 (EU), eight companies (including Pfizer) have launched generic versions of atorvastatin.

In addition, the drug was likely to dominate Teva’s manufacturing facilities for active ingredients and pill formulations.

Pfizer has stopped marketing Lipitor where its patent has expired, meaning that the brand’s $13bn annual revenue is up for grabs.

Teva Americas CEO William Marth said: “It’s a tough decision, a hard decision not to launch at this time. That doesn’t mean that sometime in the future we may not launch atorvastatin.”

Referring to the challenge of manufacturing the world’s most widely prescribed drug, he added that the reason for the decision was “when we looked at our product, we only had it in the 30-tablet bottle”.

Ranbaxy has earned $600m from atorvastatin in the US under the company’s 180-day exclusivity period (now expired) as the first generic supplier. Half of that went to Teva by agreement.

NHS diabetes services in England are failing to deliver adequate care and allowing too many patients to develop complications, the National Audit Office (NAO) has said.

The NAO estimates that the NHS spent £3.9bn on diabetes services in 2009–10, but only half of patients received the recommended standards of care.

It recommends only paying GPs for diabetes care if they provide all nine relevant care processes, including a range of tests.

According to the NAO report, the achievement of treatment standards and expected levels of care for diabetes is poor, with no PCT delivering adequate care to all its diabetes patients.

Only half of people with diabetes received the recommended standards of care in 2009–10, though this is an improvement on the 36% achieved in 2006–07.

Fewer than one in five people with diabetes are receiving the recommended tests to measure blood glucose, blood pressure and blood cholesterol.

The NAO states that the variation in the quality of care received by people with diabetes “cannot be explained by need or spending alone and is likely to be influenced by the local organisation and management of health services”.

Amyas Morse, head of the NAO, said: “The expected 23% increase by 2020 in the number of people in England with diabetes will have a major impact on NHS resources unless the efficiency and effectiveness of existing services are substantially improved.”

Among the NAO’s recommendations are:

• GPs should only be paid for diabetes care if they deliver all nine of the recommended care processes, including tests for complications and risk factors.

• The NHS Commissioning Board should “introduce effective systems of governance and accountability” to minimise inequalities in diabetes care.

Pfizer has dropped attempts to market its cholesterol-lowering drug Lipitor (atorvastatin) in the US, nearly five months after its patent expiry.

The company said its post-expiry marketing campaign had been successful, but generic erosion of the Lipitor brand would soon escalate.

The decision is a milestone in the history of the world’s best-selling drug, used to help prevent cardiovascular events in high-risk patient groups.

Pfizer has ceased negotiating new contracts to sell Lipitor to health providers in the US or promoting it through sales representatives or advertising.

Following its US patent expiry on 30 November 2011, Pfizer invested $87m in sustaining the brand through doctor marketing, advertisements and price rebates. The strategy succeeded in retaining 33% of market share, bringing in $383m in the first quarter of 2012.

However, the second wave of generic atorvastatin following Lipitor’s patent expiry in the EU in May has prompted Pfizer to give up on the brand that at one time accounted for a quarter of its revenue.

The company will continue to promote the drug in emerging markets, including China, where it could still earn billions of dollars.

Teva UK has launched a generic atorvastatin tablet on the day after the expiry of UK patent protection on Pfizer’s cholesterol-lowering drug Lipitor.

According to the British Generic Manufacturers Association (BGMA), buying generic alternatives to Lipitor could save the NHS up to £350m per year.

Pfizer could lose 85% of its UK revenue from Lipitor by the end of this year.

Atorvastatin is the most widely prescribed statin, used in millions of patients worldwide to help prevent cardiovascular disease.

Kim Innes, Commercial Director at Teva, commented: “Millions of prescriptions are written each year in the UK for atorvastatin, and the availability of the generic will save the NHS millions of pounds each year.”

“The expiration of Pfizer’s patent exclusivity on Lipitor is hugely significant for the NHS and a demonstration of the valuable role generic drugs play in patient care in the UK,” said Warwick Smith, Director General of the BGMA.

Responding to recent claims that generics harm innovation, he argued: “It is generic competition that sustains innovation. Without competition from generic products, originators could continue to make their money out of established products and the patent system would simply not work effectively.”

Roche has cancelled its dal-OUTCOMES Phase III trial after its cholesterol drug dalcetrapib failed to show any clinically meaningful efficacy.

The independent Data and Safety Monitoring Board recommended stopping the study after dalcetrapib failed to show efficacy when added to standard options of care.

Hal Barron, Chief Medical Officer and Head of Global Product Development, said Roche was “disappointed” the drug didn’t “provide benefit to patients”.

The dal-OUTCOMES trial was part of the dal-HEART global programme involving six studies. More than 35,000 patients were involved in the trials – which have also been scrapped.

Patients in the dal-OUTCOMES trial were evaluated with the use of dalcetrapib when added to existing treatment options in those with stable coronary heart disease following an acute coronary syndrome.

There were no issues regarding the safety of the drug, but the outcome comes as a setback to Roche. The Swiss-based company had hoped dalcetrapib would reach ‘blockbuster’ status and saw its share price drop by 3.5% after the trial’s closure.

“We continue to be fully committed to the development of innovative medicines for people with cardiovascular disease,” said Hal Barron. “Our pipeline remains robust with 23 positive late-stage clinical trials reporting over the past 16 months and a significant increase in New Molecular Entities in late-stage development.”

The Food and Drug Administration (FDA) is considering making medications for some long-term conditions available without prescription.

The US regulatory agency will hold a public meeting to discuss whether to reclassify drugs for high blood pressure, high cholesterol, asthma and migraine in order to ease patient access.

The FDA is also considering ways to accelerate the approval of drugs for Alzheimer’s disease and rare conditions, and to improve the targeting of antibiotics to specific patient groups.

FDA Commissioner Margaret Hamburg commented: “As the science is unfolding in new and exciting ways that will give us new tools, I think we are in a position to do things differently than we have historically.”

The shifting of some long-term condition medications to OTC status would require drug companies to carry out consumer use studies in order to show that customers are able to use the medicines correctly.

Despite this hurdle, the new policy could create a new OTC market opportunity for ‘blockbuster’ branded drugs such as Lipitor, which is facing a major drop in sales due to patent expiry.

This could create a new medical model for long-term condition management where the patient consults with a pharmacist rather than a doctor.

According to Janet Woodcock, Director of the FDA’s Center for Drug Evaluation and Research, the FDA intends to expand its accelerated approval programme – currently limited to AIDS and cancer drugs – to drugs for Alzheimer’s disease and rare conditions.

Woodcock also said that in order to counter the spread of antibiotic resistance, which has “reached crisis proportions”, the FDA plans to allow companies to test new antibiotics on smaller patient groups, and to restrict prescribing to more closely defined patient populations.

These changes, which have implications for many pharmaceutical companies selling into the US market, are intended to address urgent unmet medical needs in the US population.