B29N(epsilon)-omega-carboxypentadecanoyl-gamma-L-glutamyl desB30 human insulin

Novo Nordisk has announced that the European Commission has approved its Tresiba and Ryzodeg drugs fro the treatment of diabetes in adults.

Tresiba (degludec), a long-acting basal insulin analogue, is widely tipped to become a blockbluster drug.

It has already been approved in Japan and is awaiting approval from the US Food and Drug Administration.

The European Commission granted marketing authorisation for Tresiba based on studies in which the drug demonstrated a lower risk of overall nocturnal hypoglycaemia – common in people who treat their diabetes with insulin – compared to insulin glargine.

The treatment, with a duration-of-action beyond 42 hours “is the first basal insulin to offer patients the possibility of adjusting the time of injection, when needed,” Novo Nordisk said in a statement.

Ryzodeg, the brand name for insulin degludec / insulin aspart, can be administered once or twice-daily with the main meals.

In a treat-to-target study, this drug also demonstrated a lower risk of overall and nocturnal hypoglycaemia while successfully achieving equivalent reductions in HbA1c (glycated haemoglobin) when compared to Novo’s NovoMix (biphasic insulin aspart).

Novo Nordisk executive vice president and chief science officer Mads Krogsgaard said; “These marketing authorisations constitute significant milestones for Novo Nordisk and the treatment of diabetes.”

The Danish company expects to launch Tresiba in the UK and Denmark during the first half of 2013 and in other European markets throughout the rest of 2013 and 2014.

Ryzodeg is currently expected to be launched a year later.

“We look forward to making Tresiba and Ryzodeg available to many people with diabetes in Europe,” said Krogsgaard.

Insulin degludec is a ultralong-acting basal insulin analogue being developed by Novo Nordisk under the brand name Tresiba.^[1] It is injected subcutaneously three-times a week to help control the blood sugar level of those with diabetes. It has a duration of action that lasts up to 40 hours, unlike the 18 to 26 hours provided by current marketed long-acting insulins such as insulin glargine and insulin detemir.^[2][3]

Insulin degludec is a modified insulin that has one single amino acid deleted in comparison to human insulin, and is conjugated to hexadecanedioic acid via gamma-L-glutamyl spacer at the amino acid lysine at position B29.

Insulin degludec is an ultra-long acting insulin that, unlike insulin glargine, is active at a physiologic pH. The addition of hexadecanedioic acid to lysine at the B29 position allows for the formation of multi-hexamers in subcutaneous tissues.^[4] This allows for the formation of a subcutaneous depot that results in slow insulin release into the systemic circulation.^[5]

1.  CHMP (October 18, 2012), “Summary of opinion 1 (initial authorisation): Tresiba”, Pending EC decisions (EMA), retrieved November 6, 2012
2. “Good News for Novo’s Thrice-Weekly Insulin”.DiabetesInControl.com. Retrieved 2010-11-07.
3. Schwartzkopff, Frances (2010-06-25). “Novo’s Degludec Insulin as Effective as Lantus With Fewer Doses”.Bloomberg Businessweek. Retrieved 2010-11-07.
4. Nasrallah, SN; Reynolds, LR (2012). “Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?”. Clinical medicine insights. Endocrinology and diabetes 5: 31-7. PMID 22879797.
5. Robinson, JD; Neumiller, JJ; Campbell, RK (2012 Nov 2). “Can a New Ultra-Long-Acting Insulin Analogue Improve Patient Care? Investigating the Potential Role of Insulin Degludec.”.Drugs. PMID 23145524.
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DR ANTHONY MELVIN CRASTO Ph.D

amcrasto@gmail.com