Tresiba Gets FDA Approval

On September 25, 2015, the FDA announced it had approved two new insulin products, Tresiba and Ryzodeg, to treat people with Type 1 diabetes and Type 2 diabetes. Both have been developed by Novo Nordisk. Of the two, Tresiba is the bigger deal, as it is a rare new long-acting basal insulin and its development and approval have been a long time coming.

Ryzodeg 70/30 is an insulin product that is a mixture of 70 percent long-acting insulin (Tresiba) and 30 percent rapid-acting insulin.

Novo Nordisk officials emphasized two main selling points of Tresiba – that it is very long lasting and that it offered greater flexibility in dosing time. According to trial data gathered for the approval process, the insulin had a half life of 25 hours and stayed in the bloodstream for 42 hours, making it the longest-lasting basal insulin available. Also, a dose could be administered anytime after 8 hours of the previous dose. This means that Tresiba has the potential to lower overall injections for people with diabetes and could help those with diabetes who accidentally skip their dosing time. Novo Nordisk doesn’t formally recommend flexible dosing times, but variability in dosing or skipped doses happens, according to Robert Clark, vice president of regulatory affairs for the company.

“35 percent of patients miss one or more of their insulin doses, or fail to take them as prescribed. On average, patients miss 3.4 doses every month,” Clark stated during a 2012 FDA scientific advisory panel meeting on Tresiba, according to the meeting’s minutes. “The development of a basal insulin that would allow patients to manage unexpected missed or delayed doses should improve overall treatment adherence to and effectiveness of insulin therapy.”

In theory, that flexibility in dosing time could mean lower rates of hypoglycemia than with other basal insulins, but so far the FDA has not granted Novo Nordisk the right to tout this potential benefit on the Tresiba label. This worried company investors in a recent conference call discussing FDA approval of Tresiba and Ryzodeg. Novo Nordisk’s CEO Lars Rebien Sørensen and Chief Science Officer Mads Krogsgaard Thomsen assured investors that the FDA sets a very high bar for granting a drug company the right to say its insulin causes fewer bouts of hypoglycemia. They also said that trial data seemed to show that Tresiba and Ryzodeg did indeed cause fewer bouts of hypoglycemia, and further testing is being done to strengthen that assertion. Company officials were confident that the benefits that the FDA allows Novo Nordisk to advertise will be enough to attract a market.

“We have a nice label where you can say it’s an insulin with the longest half-life providing the longest duration of action,” said Krogsgaard Thomsen in the conference call.

Such benefits were apparently enough to convince federal regulators to approve Tresiba and Ryzodeg after initially rejecting the two in 2013 over concerns that the insulins caused a slight increased risk of cardiovascular problems. If true, that would be a big concern, as a sizeable amount of people with diabetes, both Type 1 and Type 2, are already at high risk of cardiovascular problems. That was a concern expressed by Dr. Charles Shaefer, a Georgia primary care doctor, during the 2012 FDA advisory panel meeting.

tresiba_mesa_300px“We’ve seen evidence this morning to at least raise the question of whether there may be minor increases in adverse cardiovascular events in actively treated patients with (Tresiba),” Dr. Shaefer said.

Several advocates for the diabetes community asserted at the same meeting that new insulin development was worth the possible slight increase in risks of cardiovascular issues. Kelly Close, editor of diaTribe, pushed back at the possibility that the FDA could ask Novo Nordisk for additional cardiovascular data before granting approval of Tresiba and Ryzodeg; to her, such a move could have a chilling effect on investment in new insulins.

“If FDA is going to require pre-approval cardiovascular outcome trials, it would be the equivalent of changing the goalpost in the middle of the game,” Close said at the meeting.

After the 2013 FDA rejection, Novo Nordisk worked to collect trial data to assuage federal regulators of the cardiovascular safety of Tresiba and Ryzodeg. However, the drug company didn’t wait until its clinical data was complete, instead choosing to resubmit for approval in March. It was seen as a gamble at the time by industry analysts, but it paid off.

Tresiba and Ryzodeg already are available for sale in Japan and much of Europe. However, the rollout has had a few bumps in the road. Most notably, Novo Nordisk pulled Tresiba from the German marketplace in October 2015 after an argument with German health regulators, according to an article in MedScape Speciality. The fight started in 2014, when the the German Institute for Quality and Efficiency in Health Care declared that Tresiba failed to offer any real benefit over existing insulins on the marketplace; this blocked Novo Nordisk from offering their insulin at the price Novo Nordisk wanted. Many diabetes advocates in Germany were frustrated with the move to pull the insulin from the marketplace, saying it caused chaos for some patients already on Tresiba and blocked the availability of an insulin option for people with diabetes.

Tresiba and Ryzodeg will be entering a basal insulin marketplace currently dominated by Sanofi, which enjoyed some $7 billion in sales in 2014 for its flagship basal insulin, Lantus. Sanofi hopes to replicate that success with its new basal insulin, Toujeo, released this past year. It also has fiercely fought in court any attempts to create generic forms of Lantus. This past month, Sanofi settled a longstanding lawsuit with Eli Lilly and Company over Lilly’s attempts to sell a generic formulation of Lantus, according to a FiercePharma report. Under the agreement, Lilly will pay licensing fees to Sanofi for some Sanofi patents and pledge not to roll out a Lantus generic before December 15, 2016. That gives Sanofi a window to establish Toujeo before a generic form of Lantus hits the marketplace.

In the investor conference call, Novo CEO Rebien Sørensen detailed that the company is prepping for a commercial rollout for Tresiba and Ryzodeg in early 2016, while making the insulins available to some medical specialists and pharmacists in the last quarter of 2015. FiercePharma reports that the company has made a significant investment in its sales force in preparation of the Tresiba rollout.

However, Rebien Sørensen said the company will not try and use its entire portfolio of insulin products to try and create exclusive package deals to entice doctors to use Tresiba instead of Lantus or other basal insulins. Novo Nordisk also won’t offer extensive discounts on Tresiba to compete with Lantus or Toujeo. Rebien Sørensen said the drug will be offered at a “premium price” because of its potential to outperform other basal insulins. The company is betting that this will create market demand. Rebien Sørensen told investors they should expect Tresiba to gain a small foothold in the marketplace in the early stages and then increase that marketshare over time.

“We’d rather have a more steady penetration into the marketplace given that we believe we have the premium product,” Rebien Sørensen said in the conference call.

If the company’s basal insulin products get a foothold in the U.S. marketplace, they will provide greater basal insulin choice for people with diabetes. Also, if Novo Nordisk’s new products prove a real threat to Sanofi’s continued dominance of the basal insulin marketplace, that could also create downward pressure on basal insulin prices. With FDA approval, now we get to see if such projections will pan out.

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Craig Idlebrook is a past editor for Insulin Nation, Type 2 Nation, and Información Sobre Diabetes. He is now the community engagement and content manager for T1D Exchange.

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