Insulin degludec - Tresiba; recombinant; NN1250
Status: EU approved in Jan. 2013; NDA rejected (CRL) in Feb. 2013
Organizations involved:
Novo Nordisk A/S – Manuf.; R&D; Tech.; World mark.
Description: Insulin degledec is an ultralong-acting insulin analog, presumably microbially expressed (by a yeast or E. coli bacteria). Insulin degludec has one single amino acid deleted in comparison to human insulin, and is conjugated to palmitic acid at the amino acid lysine at position B29 Insulin degludec has a calculated molecular formula of C274H411N65O81S6 with molecular weight = 6.104 kDa.
Note, Novo Nordisk is seeking simulataneous approval of Tresiba (insulin degledec) and Ryzodeg, the combination of insulin degludec and iinsulin aspart (marketed as NovoLog)
Nomenclature: Tresiba [TR]; Ryzodeg [TR; combination of insulin degludec plus insulin aspart]; Insulin degludec [USAN INN]; Insulin degludec (genetical recombination) [JAN]; (1A-21A),(1B-29B)-Insulin (human), 29B-[N6-[N-(15-carboxy-1-oxopentadecyl)-L-γ- glutamyl]-L-lysine]- [CAS]; N6,29B-[N-(15-carboxypentadecanoyl)-L-γ-glutamyl]-des-30B-L-threonine-human insulin [CAS]; 844439-96-9 [CAS RN]; D09727 [TR]; NN1250 [SY]
Companies.: Novo Nordisk developed, manufactures and will market insulin degludec worldwide.
FDA class: Drug NDA
Status: The NDA was filed in Nov. 2011 and had a FDA PDUFA (target approval date) of July 29, 2012. This was delayed to Oct. 29, 2012, after FDA asked for and received additional data.
In late July 2012, FDA scheduled an advisory committee meeting to consider approval on Nov. 8, after the PDUFA date, meaning further delay in approval. In Nov. 2012, the FDA Endocrinologic and
Metabolic Drugs Advisory Committee
unanimously recommended that a cardiovascular outcomes trial should be conducted and
voted eight to four in favor of approving the products with a post-approval
cardiovascular outcomes trial commitment.
On Feb. 11, 2013, FDA rejected the NDAs for Tresiba and Ryzodeg, issuing a Complete Response Letter (CRL), with additional cardiovascular data from a dedicated
cardiovascular outcomes trial required before the review of the New Drug Applications can be
completed. This will likely delay FDA approval until 2015 or 2016.
Japan approved Tresiba in Sept. 2012, becoming the first country to do so.
Trials: In April 2012, two Phase III trials with insulin degludec were published in The Lancet generally showing that insulin degludec considerably reduced rates of nocturnal hypoglycemia in patients with type 1 and type 2 diabetes by 25%, compared to insulin glargine. 1,635 individuals with diabetes were enrolled to participate in the trials in order to examine insulin degludec, compared to insulin glargine, in a basal-bolus regime. In both studies, researchers adjusted patient insulin doses systematically in order to allow them to achieve a targeted fasting glucose level. Due to this, participants in both studies successfully achieved similar improvements in sugar control; and this allowed the researchers to closely determine disparity in hypoglycemia rates. Subjects with type 2 diabetes who took insulin degludec had a considerably lower rate of overall hypoglycemic events (11.1 episodes/patient-year), compared to individuals assigned to insulin glargine (13.6). This figure was similar between both groups in individuals with type 1 diabetes. Results also showed that insulin degludec reduced nocturnal hypoglycemia by 25% in both type 1 and type 2 diabetes (4.4 vs 5.9 episodes/patient-year), compared to participants taking insulin glargine (1.4 vs. 1.8).
Market: The primary competition for insulin degludec is Lantus (insulin glargine).
Index Terms:
Companies involvement:
Full monograph
195.1 Insulin degludec, rDNA
Nomenclature:
Tresiba [TR]
Ryzodeg [TR; combination of insulin degludec plus insulin aspart]
insulin degludec [USAN INN]
Insulin degludec (genetical recombination) [JAN]
(1A-21A),(1B-29B)-Insulin (human), 29B-[N6-[N-(15-carboxy-1-oxopentadecyl)-L-γ- glutamyl]-L-lysine]- [CAS]
N6,29B-[N-(15-carboxypentadecanoyl)-L-γ-glutamyl]-des-30B-L-threonine-human insulin [CAS]
844439-96-9 [CAS RN]
D09727 [TR]
NN1250 [SY]
nsulin degludec plus insulin aspart [SY]
molecular weight (kDa) = 6.104
FDA Class: Drug NDA
biopharmaceutical products
hormones
hyperglycemia
insulin, recombinant human
recombinant DNA
EU200 Currently Approved in EU
UM999 Not Available/Not Marketed in US
US01 FDA application withdrawn or rejected
EM001 Marketed Product in EU
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