iDegLira
iDegLira (NN9068) is a combination of Tresiba® (insulin degludec), a once-daily ultra long acting insulin analog; and Victoza® (liraglutide), a once-daily human GLP-1 analogue. It is also known as Xultophy. Victoza is long-acting glucagon-like peptide-1 receptor agonist. The GLP-1 receptor when activated stimulates the adenylyl cyclase pathway. This stimulation kicks off the insulin synthesis process.
Normally a hormone appropriately named GLP-1 binds to the receptor and stimulates the process described. In patients that suffer from type II diabetes, artificial stimulation through a GLP-1 receptor agonist such as Victoza can mimic the natural process, and help the body generate additional insulin. Victoza is a once daily, subcutaneous injection administration therapy.
Tresiba is insulin degludec, which is just an extra long acting insulin treatment that lasts up to 42 hours. The addition of hexadecanoic acid to one of the amino acids enables the insulin to form stable hexamers easily in the blood, keeping it inactive, which is where its ultra-long acting nature comes from. It is currently available as a once daily injection, and is Novo’s fifth most popular diabetes product in terms of revenues generated. iDegLira combines the receptor agonist with the long-lasting effects of degludec.
The market
The potential for this one is big, but overlapping with what is already available from Novo. The combination drug is already approved in Europe, and generated revenues that amounted to just shy of 2% of the company’s total sales during 2015. This is tiny compared to what an approval in the US might mean for Novo, however. Analysts expect peak sales somewhere in the region of $1 billion, but this could improve if the company picks up some favorable labeling come PDUFA. Most of the sales will cannibalize from current Tresiba and Victoza sales, but not entirely. Despite the overlap, it is still important for Novo to get iDegLira approved to keep up with the Jones’s at Sanofi SA (ADR) (NYSE:SNY) and maintain market share.
Current Status
From a development perspective, iDegLira is the closest to an FDA green light of all the drugs covered here. Novo submitted its NDA last year, and an FDA review panel just voted unanimously in favor of an approval for the candidate. One thing to bear in mind, however, is that this is the second time the company has submitted an NDA for this target. The first time, the FDA requested more information on long term cardiovascular risks associated with the once daily administration regimen. Novo has now provided that data, and while questions still remain as to the long term safety of the product, prospects look good.
The efficacy data on which the NDA is based is top notch, and safety at least in the near to medium term doesn’t look to be an issue. With a unanimous panel recommendation in the bag, Novo could be targeting the billion dollar estimated market before the year draws to a close, preserving its base.
Semaglutide
Semaglutide is another GLP-1 receptor agonist, and another by Novo Nordisk A/S (ADR) (NYSE:NVO). It works like other GLP-1 receptor agonists as described above with one difference. Semaglutide is designed for weight loss. GLP-1 receptor agonists have a benefit over traditional insulin administration treatments in that they contribute to a reduction in body fat in patients that suffer from the disease, thought to be due to a delay in gastric emptying. Novo is attempting to prove the weight loss effect in its trials.
Current Status
Two recently completed Phase III trials dubbed SUSTAIN 2 and SUSTAIN 3 were run for this candidate. SUSTAIN 2 looked at semaglitude versus Januvia, covered in Part I, a currently approved antidiabetic DPP-4 inhibitor from Merck and Co., Inc. (NYSE:MRK). DPP-4 breaks down GLP-1, so inhibiting DPP-4 increases GLP-1, which increases insulin production. SUSTAIN 3 compared semaglitude to an AstraZeneca plc (ADR) (NYSE:AZN) GLP-1 agonist called exanatide, or commercially, Byetta.
Both trials just reported positive top-line results showing a statistically significant improvement in insulin-related impact and the SUSTAIN 3 trial showed an improvement in the weight loss side of the drug versus its AstraZeneca counterpart.
The future is likely a little more drawn out than some of the other candidates on the list, however. There are five more Phase 3 trials planned before Novo will consider its development process completed, and so we are probably looking at some point in 2018 before the company gets around to submitting an NDA. Beyond that, approval (assuming safety and efficacy replicates across the remaining five trials) is expected closer to 2020.
