UK Watchdog Turns Down Liraglutide (Saxenda) for Obesity

Liam Davenport

January 30, 2020

Obese patients in England are unlikely to be prescribed the weight loss medication liraglutide (Saxenda, Novo Nordisk) on the UK National Health Service (NHS) any time soon after the national watchdog said, in draft guidance, that it will not be recommending the drug.

The National Institute for Health and Care Excellence (NICE) said that any estimates of cost-effectiveness for liraglutide for obesity were "highly uncertain" and "potentially much higher" that would be an acceptable use of healthcare resources.

This is despite Novo Nordisk recommending that the drug be restricted to individuals referred to specialist centers who have a high body mass index (BMI), are at risk of type 2 diabetes (with prediabetes), and are at high risk for cardiovascular disease.

The draft guidance was published on January 24 and is now open for consultation until February 14. NICE says that, following the consultation period, it will consider any comments received by the closing date before preparing the final appraisal.

Liraglutide, a subcutaneous injectable glucagon-like peptide 1 (GLP-1) agonist, is already marketed for the treatment of type 2 diabetes as Victoza, which NICE has recommended. The drug was approved at a higher dose (3 mg) for use in obesity, as Saxenda, by the European Union in 2015, but individual member states of the European Union make their own decisions about reimbursement.

"Disappointing" Decision

Fundamental to the decision that liraglutide should not be recommended for use in obesity was a lack of evidence provided for the full population covered by the marketing authorization, and a model that estimated the incremental cost-effectiveness ratio (ICER) for each quality-adjusted life-year (QALY) gained of over £100,000 (approximately $130,000) if only the effects of the drug on BMI are considered.

And a report by FiercePharma also suggests that NICE was deterred by the price of liraglutide, listed at £196.20 (approximately $255) for 5 x 6 mg/mL 3-mL (18-mg) prefilled pens, despite the presence of a "confidential discount" from the manufacturers.

In a statement, Adam Burt, Obesity Director at Novo Nordisk UK, said the company is "committed to working with NICE...and we are developing our response."

He underlined that there are "currently very few treatment options available" for obesity and they hope a combination of liraglutide, diet, and exercise "can make an important contribution to helping people living with obesity," particularly those at risk of type 2 diabetes and cardiovascular disease.

Sarah le Brocq, director, Obesity UK, added: "There are few treatment options available and I hope that NICE will look closely at the evidence to make the best choice for people living with obesity."

And Matthew S. Capehorn, MBChB, described the decision as "disappointing." Capehorn is clinical manager at the Rotherham Institute for Obesity, UK, and medical director of LighterLife, a weight loss company,

Difficult to Quantify Risk of a Comorbidity

Capehorn told Medscape Medical News that, having been a principal investigator on the pivotal trials of liraglutide in obesity, "I've got lots of first-hand experience of just how effective it is."

"Good responders can lose up to a stone (14 lb or 6.4 kg) per month, and we've been desperate for really, really good, effective weight loss medications for such a long time," he said.

"It's a bit of surprise that NICE have taken this view, especially given the fact that I'm aware that Novo Nordisk put additional safeguards in and additional criteria for prescribing it to make it not only more cost-effective, but also to prevent it being abused by your average GP just prescribing it through patient pressure," he noted.

Capehorn continued that it can be difficult to perform health economic modeling for conditions such as obesity, as it is difficult to quantify the risk of a patient developing a comorbidity.

Taking type 2 diabetes as an example, he said: "How do you prove that that particular patient was going to be the one that was going to develop diabetes? And how do you prove how long you delayed the onset of diabetes for, by that amount of weight loss?"

"It could be by several years — 5 or 10 years — and there's not just a health gain to the patient, but a financial gain to the NHS with that. But how do you quantify it?" he added.

In its draft guidance, NICE does acknowledge that the current options for obesity "are limited and there is a need for a treatment that deals with biological determinants of obesity."

It also agreed with the company's decisions to focus on individuals with a BMI of at least 35 kg/m2, prediabetes, and a high risk of cardiovascular disease, and to propose that liraglutide be made available only through specialist, multidisciplinary services.

NICE Has Reservations About a Subgroup Analysis of SCALE

However, NICE said it has "reservations" about the use of a posthoc subgroup analysis of trial 1839 (SCALE study) to estimate the effectiveness of liraglutide in the proposed population, saying the evidence "may not be reliable."

It also pointed to the lack of a significant reduction in cardiovascular outcomes with liraglutide versus placebo and highlighted the "uncertainty" around relying on surrogate markers.

Doubts were also raised about the company's suggestion that all patients who have an initial weight loss of over 5% would stop treatment at 2 years.

"The clinical experts explained that people who have lost weight are likely to want to continue taking the treatment," the draft guidance states, adding, "This was confirmed by the patient expert."

And when it came to the economic model submitted by the company, NICE said it was "suitable" but that there were "uncertainties" about the way in which cardiovascular risk was estimated.

It also questioned the assumption that all people who have a cardiovascular event develop type 2 diabetes in the following year, saying there is "no good evidence" to determine who will develop the condition.

The guidance says the company's model suggested the ICER for liraglutide would be £105,000 (approximately $136,000) per QALY gained if only BMI was included.

This would fall to just under £50,000 (approximately $65,000) per QALY if diabetic benefits were added, and just over £21,000 (approximately $27,000) if additional cardiovascular benefits were included.

This prompted NICE to say that "further explanation and justification" would be needed for it to "be persuaded that liraglutide was cost-effective."

NICE did note, however, "The clinical experts also explained that people who experience side effects with minimal weight loss are most likely to stop taking the treatment."

Capehorn has reported being a principal investigator for pivotal trials of liraglutide in obesity.  He is an expert advisor to NICE. He has received honoraria for advisory boards or speaker meetings and/or expenses to attend conferences from Novo Nordisk, Boehringer Ingelheim/Lilly Alliance, Janssen, Novartis, GlaxoSmithKline, and Syneos Health. The Rotherham Institute for Obesity has received research funding from LighterLife, Novo Nordisk, Boehringer Ingelheim/Lilly Alliance, Janssen, Novartis, MSD, Leo, GlaxoSmithKline, and Syneos Health.

NICE. Liraglutide for managing overweight and obesity [ID740]. Project documentation

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