EP Vantage Interview – Novo shooting for broad use of insulin degludec

Novo Nordisk’s new ultra-long-acting insulin analogue, degludec, has the potential to be the strongest competitor in the space now dominated by Sanofi-Aventis’ Lantus. A series of phase II study results released at the American Diabetes Association scientific sessions showed insulin degludec may be able to achieve blood-glucose control with fewer hypoglycaemic episodes.

So as a new product likely to command a premium price, one might expect that Novo will be targeting a small number of patients, perhaps those having difficulty controlling their blood glucose with well-established human insulins on the market for decades. But this is not the case, Mads Krogsgaard Thomsen, Novo’s executive vice president and chief science officer, tells EP Vantage in an interview at ADA.

“Every patient should have this,” Mr Thomsen says. “Patients will have a reduced risk of either hypoglycaemia at the peak (of the insulin curve) or hyperglycaemia at the trough.

“Very often Levemir and Lantus do not give you 24-hour control, and physicians know it,” he adds. “Most of them just have to live with what they have, and (with degludec) they can get something where it’s not an issue because it acts for so much longer.”

Commercial concerns

Proving effectiveness is one thing. Persuading insurers in the US and government regulators in many other countries that degludec will be worth the premium price for the broad population of patients is another.

Mr Thomsen, however, says he believes a health economic case can be built in favour of degludec. For example, type 1 diabetics, of which there are as many as 500,000 in the US, suffer one hypoglycaemic episode a week, so a 30-50% reduction in these episodes will show a benefit through prevention of hospitalisation, he says.

Type 2 diabetes is much more prevalent, but patients have fewer hypoglycaemic episodes. “But even in type 2 diabetes, Lantus has commanded a good reimbursement status as a tier II product in the US, and if we compare Lantus to degludec once daily and can show it has at least 30% benefit on hypoglycaemia, then we can come up with some kind of premium price,” Mr Thomsen says.

Lantus on top for now

Although it is facing safety scrutiny, Lantus remains the dominant force in the long-acting insulin space (ADA – Experts rally round Lantus, June 28, 2010). According to EvaluatePharma, sales last year of $4.29bn will grow to $6.21bn in 2014, before its patent expiry in 2015 although generic competition is still expected to be limited as sales in 2016 are still significant at $4.9bn.

Novo's long-acting insulin competitor, Levemir, still significantly trails Lantus with sales in 2009 of $978m expected to reach $2.49bn by 2016. The unknown factor in the space is the introduction of Novo’s degludec, now expected in 2013 and expected to bring Novo an additional $294m in sales in 2016.

There remains some question as to whether generic competitors will be able to successfully navigate the biosimilar pathway set out for the FDA in the new health care reform law in the US (BIO 2010 - Biosimilar pathway cleared in US but will any company set foot on it?, May 6, 2010). Thomsen said Novo’s strategy assumes one will and thus needs to be on the market before the biosimilar is introduced – hence it is targeting a 2013 launch.

Making a splash

Novo used the ADA meeting to make a splash with five separate presentations on degludec proof-of-concept phase II results, consisting of tests of degludec alone in type I and II diabetes as a once daily treatment, three times a week, or in combination with NovoRapid, against Lantus, known as insulin glargine.

Compared with Lantus, insulin degludec or the degludec/NovoRapid combination achieved similar reduction in blood glucose levels under a trial protocol that required an increase in dosage until HbA1C levels of 7% were achieved.

These results suggest reductions in hypoglycaemic episodes - although as a small trial proving statistical significance was difficult. The combination of degludec with NovoRapid also confirmed reductions in nocturnal hypoglycaemic episodes, better post-dinner plasma glucose control and achieved the same blood glucose control at a lower dose.

Mr Thomsen acknowledges that the trials do not show superior blood glucose reductions, although he says the treat-to-target protocol, mandated by regulatory authorities, is not designed to do so. In a real-life setting, he says, the dosage is limited by episodes of hypoglycaemia, and an insulin that can achieve glucose control with fewer occurrences of hypoglycaemia is likely to be a preferred product.

The findings are awaiting validation in the phase III Begin and Boost trials, which are enrolling more than 10,000 patients.

It is still a long way from phase II to approval, of course, but the signs for insulin degludec appear to be good. Science aside, the remaining task is likely to be persuading insurers and regulators that degludec represents good value.

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