A US consumer group has called on the FDA to withdraw its approval of Novo Nordisk’s injectable diabetes drug Victoza on safety grounds.

Public Citizen cited evidence that Victoza is associated with increased rates of pancreatitis and kidney failure, as well as causing thyroid cancers in rodents.

Novo Nordisk commented that the evidence cited in the petition is adequately covered by Victoza’s label.

The FDA approved Victoza in 2010 against the recommendation of three staff scientists, the consumer group claimed.

One of them, Dr Karen Mahoney, wrote in an FDA memo: “The need for new therapies for Type 2 diabetes is not so urgent that one must tolerate a significant degree of uncertainty regarding serious risk concerns.”

The FDA had noted that Victoza caused thyroid tumours in rats and mice. The product label states that it is “unknown” whether the drug could have a similar effect in humans, and recommends that patients with a family history of thyroid cancer should avoid the drug.

Similarly, Victoza’s label refers to the increased risk of pancreatitis and to certain incidents of kidney failure.

Public Citizen noted that in the first 17 months of Victoza’s use, the FDA received 200 reports of patients diagnosed with pancreatitis. The group estimated that only 10% of actual cases were reported.

Novo Nordisk said the FDA’s approval was based on extensive studies involving more than 4,000 patients, and that since then the company “has continued to work closely with the FDA and the medical community to monitor the benefits and appropriate use” of the drug.

Novo Nordisk’s Chief Science Officer, Mads Krogsgaard Thomsen, commented that the rodent studies were of no relevance to human patients. “We do not expect any consequences for Victoza from Public Citizen’s petition,” he said.

NHS spending on drugs fell in 2011 due to patent expiry affecting a number of major products – and 2012 will see the trend accelerate.

The NHS in England spent £8.81bn on prescription drugs in primary care last year, compared to £8.83bn in 2010, according to the NHS Information Centre.

This fall, which reflects pressure on GPs to reduce their drug budgets, contrasts with the previous trend of drug spending increasing by 3–4% each year.

Therapy areas where the NHS pharmaceutical market was strongly affected by patent expiry in 2011 include cardiovascular care and CNS disorders – while diabetes care showed a new trend towards the selection of cheaper drug classes.

Cardiovascular drugs showed the steepest drop in sales: from £1.51bn in 2010 to £1.35bn in 2011. A major factor in this was the generic erosion of the anti-platelet drug Plavix from Sanofi and BMS, revenues from which fell from £46m to £12m.

By contrast, NHS spending on Pfizer’s statin Lipitor increased by £5m to a massive £310.8m – but that blockbuster will fall over the patent cliff in May, with wholesale shifting of GPs to generic versions expected.

The NHS spent £1.95bn on drugs for CNS disorders last year, but this therapy area is facing major generic erosion due to the recent patent expiry of AstraZeneca’s antipsychotic Seroquel and Pfizer and Eisai’s Alzheimer’s drug Aricept, which between them cost the NHS £170m in 2011.

In diabetes care, growing demand and the impact of new treatments is balanced by growing cost pressure forcing a retreat to older and cheaper drugs.

On the one hand, spending on Novo Nordisk’s new injectable GLP-1 drug Victoza increased from £9.6m to £21.9m last year, while AstraZeneca’s new oral medicine Januvia saw its revenue rise from £27m to £45m.

On the other hand, NHS spending on Novo Nordisk’s fast-acting insulin NovoRapid fell from £63.4m to £62.7m last year, due to pressure from the National Prescribing Centre to switch to the cheaper isophane insulin.

The UK pharmaceutical market thus faces both generic erosion and a new trend towards the choice of drug classes that reduce costs, but may not represent the standard of care.

GlaxoSmithKline (GSK) has reported successful phase III trials of its new diabetes drug albiglutide, which it intends to file for regulatory approval.

The injectable drug, taken weekly, outperformed a rapid-acting insulin when used in combination with a daily insulin to manage type 2 diabetes.

Analysts predict the drug will earn GSK $250m per year by 2016 – not a potential ‘blockbuster’, but a robust product in the diabetes market.

Albiglutide – awaiting a new brand name after GSK dropped the name Syncria – is the latest product in the class of glucagon-like peptide-1 (GLP-1) diabetes drugs that includes Victoza from Novo Nordisk and Byetta from Amylin and Lilly.

GLP-1 drugs stimulate insulin release when glucose levels are high, a flexible property that makes them a potential alternative to insulin in patients with severe type 2 diabetes.

They have the further advantage of stimulating weight loss, which is of clinical value to most people with type 2 diabetes.

The first phase III trial of albiglutide, reported in November 2011, found it to be less effective than daily Victoza in reducing blood glucose levels – a disappointing result for GSK.

However, armed with top-line results from seven of eight phase III studies, GSK said that the cumulative data support an application for the drug’s approval as a treatment for type 2 diabetes.

One trial tested albiglutide against Lilly’s rapid-acting insulin Humalog when used in combination with Sanofi’s daily insulin Lantus.

The patients taking albiglutide experienced a 0.82 reduction in HbA1c, compared to 0.66 in the Humalog group. In addition, The albiglutide patients also lost an average of 0.73 kg in weight, whereas the Humalog patients gained 0.81 kg.

GSK expects to have all the data it needs to apply for regulatory approval by the end of 2012.

Novo Nordisk has increased operating profits by 12% in the first nine months of the year after sales growth rose due to the performance of Victoza (pictured), NovoRapid and Levemir.

Sales of modern insulins increased by 11% after Victoza sales nearly DKK 3.9 billion which resulted in net profit jumping nearly a fifth (19%) to DDK 12.4 billion.

Lars Rebien Sørensen, President and CEO, says Novo is “pleased” to see its key products “drive strong underlying sales growth”.

The Danish-based company has now updated its outlook for the year and expect sales growth to be between 10%-11% and operating profits growth be in the region of 17%-19%.

In North America sales increased by 17% and in other International Operations by 16%. Gross margin improved by 0.2% which Novo says reflects a favourable product mix development due to an increase in sales of modern insulin versus lower human insulin sales.

Regulatory dossiers for the company’s new generation of insulins, Degludec and DegludecPlus, were also submitted to the European and US authorities in September. “The filing of our new-generation insulins, ultra-long-acting Degludec and DegludecPlus, in the US and Europe is a major milestone in the expansion of our leadership in diabetes care."

Novo has now adjusted its preliminary outlook for next year which indicates a high single-digit sales growth and an operating profit increase near 10%.

The company increased its operating profit by nearly a third in 2010.

The CHMP has given a positive opinion to Novo Nordisk’s basal insulin analogue Levemir as an add-on treatment in patients with type 2 diabetes.

The opinion is based on a clinical trial where, as an add-on therapy to Victoza, in combination with metformin, reduced glycated haemoglobin (HbA1C) and sustained weight loss were demonstrated.

Alan Moses, Global Chief Medical Officer at Novo Nordisk, says the decision provides an “additional treatment option” for patients who need more options to achieve personalised glucose targets.

Meanwhile, the Committee has also adopted a positive opinion on the extended use of the insulin in children aged between two and five years old with type 1 diabetes.

It reviewed data that showed children treated with Levemir plus a fast-acting insulin analogue experienced a lower rate of all-day and nocturnal hypoglycaemia when compared to those taking human basal insulin and insulin aspart.

Dr Nandu Thalange, Norfolk and Norwich University Hospital, says that when treating children their safety must always come first and welcomed the CHMP’s decision. “Reducing risk of hypoglycaemia – particularly at night – is a vital part of modern management of young children with diabetes,” said Dr Thalange. “Children under six years are at the highest risk of severe hypoglycaemia and other acute diabetes complications, and any treatment which improves safety – not least in this group – is to be welcomed.”

Novo Nordisk now anticipates that the European Commission will shortly approve the usage of Levemir as an add-on therapy to Victoza in patients with type 2 diabetes and extend the marketing authorisation to make the insulin detemir the only basal insulin analogue for the use in this young patient group with type 1 diabetes.

Levemir, Victoza and NovoRapid, another insulin therapy by Novo Nordisk, contributed to a profit increase of 27% for the company in 2010.

Novo Nordisk increased its operating profit by nearly a third last year.

Sales of Victoza, NovoRapid and Levemir resulted in an operating profit increase of 27% and a net profit rise of 34%.

Lars Rebien Sørensen, President and CEO, described 2010 as a “very good year” for the Danish company.

Novo Nordisk also reached its four long-term financial targets in 2010 as announced in their annual report for 2008.

Sales of modern insulins increased by 24%, as did sales in international operations. For 2011, Novo Nordisk now calculates sales growth measured in local currencies to be between 8% and 10%, and operating profit growth measured in local currencies is expected to be around 15%.

“We expect continued sales growth from these products and are encouraged by the results from the phase 3 programme with our new generation insulins,” said Mr Sørensen.

NICE has recommended a 1.2mg dose of Victoza (liraglutide) for the treatment of type 2 diabetes mellitus.

But it has failed to recommend a daily 1.8mg dose saying the increase did not show any “significant additional benefit”.

In final guidance, Victoza 1.2 mg in duel therapy regimens is recommended if patients are intolerant to metformin and a sulphonylurea, or treatment is contraindicated, and are also intolerant to certain inhibitors.

Type 2 diabetes affects around 2.25 million people in the UK.

Victoza 1.2mg is also recommended as part of triple therapy regimens with other advised treatments only when control of glucose remains or becomes inadequate. But patients must have a certain body mass index (BMI) and psychological or medical problems associated with high body weight; or the same BMI where insulin would have significant occupational implications, or weight loss would benefit obesity-related comorbidites.

“We are pleased to recommend liraglutide 1.2 mg daily as a clinically and cost effective treatment option for some patients with the disease,” said Dr Carole Longson, Health Technology Evaluation Centre Director at NICE.

NICE has recommended Novo Nordisk’s Victoza (liraglutide) for NHS funding, but restricted its use to a specific patient group.

In draft guidance, NICE recommended Victoza 1.2mg daily dosage in combination with metformin or a sulphonylurea if treatment with metformin or a sulphonylurea, and thiazolidinediones and dipeptidyl peptidase-4 (DPP-4) inhibitors are unsuitable.

In triple therapy regimens with metformin and a sulfonylurea, or metformin and a thiazolidinedione, Victoza is recommended only when control of blood glucose becomes inadequate and the patient has specific psychological or medical problems associated with high body weight.

NICE also ruled that treatment with the drug should only be continued if the person’s diabetes has shown a “beneficial metabolic response” within six months.

“40% of people in the UK with diabetes are at high risk of complications because their blood sugar is not being controlled as well as it needs to be. Diabetes and its complications cost the NHS around £9 billion each year,” said Viggo Birch, Managing Director, Novo Nordisk Limited (pictured).

“As a company our drive is to defeat diabetes, and ensure people receive the highest quality of care. We believe liraglutide in combination with either one or two anti-diabetic tablets can have significant benefits for people living with type 2 diabetes, and are therefore delighted NICE has recognised this.”

Due to just a marginal benefit from the increased 1.8mg dose, the Appraisal Committee decided that treatment with this formulation was not justified.

Professor Anthony Barnett, Clinical Director of Diabetes and Endocrinology, University of Birmingham and Heart of England NHS Foundation Trust, Birmingham, commented: “This is good news for healthcare professionals and their patients with type 2 diabetes. Diabetes is an enduring challenge for the NHS and liraglutide is now a valuable option available through the NHS for treating appropriate patients who we, as healthcare professionals, believe will benefit from the therapy.”

Final guidance is likely to be published in October 2010.