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Evidence-Based Diabetes Management December 2017

Medical World News: Regulatory Updates

AJMC Staff

Novo Nordisk's Fiasp for Mealtime Use Gains FDA Approval

Christina Mattina 

THE FDA HAS APPROVED Novo Nordisk’s Fiasp, an insulin aspart injection that can rapidly improve glycemic control at mealtimes for patients with type 1 and type 2 diabetes (T1D and T2D).

According to a statement from the company, the new injection is similar to the fast-acting insulin aspart NovoLog but also contains niacinamide, known as vitamin B3, which helps the body absorb insulin faster. “According to an analysis in our FDA submission, Fiasp appeared in the bloodstream in 2.5 minutes. In that same analysis, NovoLog appeared in the bloodstream in 5.2 minutes. Due to its fast onset and appearance in the bloodstream, Fiasp can be dosed at the beginning of a mealtime or within 20 minutes after the start of a meal,” said Todd Hobbs, MD, chief medical officer of Novo Nordisk in North America, in an email.

Similar to NovoLog, Fiasp will be sold in both 10-mL vials and pre filled delivery pens marketed as FlexTouch by Novo. It will also have an identical list price to NovoLog, and the statement indicates that it will be eligible for the manufacturer’s savings card and Patient Assistance Program.

While the original insulin aspart is meant to be fast acting, Fiasp and its niacinamide will help the drug act even more quickly. Speed is especially important during meals, which can lead to blood sugar fluctuations that make it difficult for people with either type of diabetes to achieve optimal blood glucose levels. Fiasp may be used at the start of a meal or within 20 minutes of when the patient begins eating.

The FDA approved Fiasp based on positive results from the Onset clinical trial program, which enrolled more than 2000 adults with T1D or T2D. In phase 2a, patients of both types had a reduction in glycated hemoglobin (A1C) levels after taking Fiasp, whether it was administered at mealtime or after they had started eating. Participants reported some adverse effects, including nasopharyngitis, upper respiratory tract infection, nausea, diarrhea, and back pain. Fiasp is not approved for children.

“With Fiasp, we’ve built on the insulin aspart molecule to create a new treatment option to help patients meet their postmeal blood sugar target,” Bruce Bode, MD, FACE, president of Atlanta Diabetes Associates and an associate professor at Emory University School of Medicine, said in the statement. “The intention of rapid-acting insulin therapy is to mimic, as much as possible, the natural physiological insulin response that occurs after meals, a process that is important for optimal A1C management.”


Novo Nordisk receives FDA approval for Fiasp, a new fast-acting mealtime insulin [press release]. Plainsboro, NJ: Novo Nordisk; September 29, 2017. Fiasp-R-a-New-Fast-Acting-Mealtime-Insulin. Accessed October 28, 2017.


CV Indication Sought for Canagliflozin, Combinations

Mary Caffrey 

JANSSEN RESEARCH & DEVELOPMENT has led a supplemental new drug application with the FDA to add a cardiovascular (CV) indication to canagliflozin, its popular therapy for type 2 diabetes (T2D) sold as Invokana. Company officials announced the application on October 2, 2017.1

In the application, Janssen also seeks CV indications for canagliflozin fixed dose combinations Invokamet and Invokamet XR, the statement said.

The filing was anticipated after a presentation in June at the 77th Scientific Sessions of the American Diabetes Association in San Diego, California, where results of the CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (CANVAS-Renal) studies showed a 14% reduction in the combined primary end point of nonfatal heart attacks, nonfatal strokes, and CV death.2 Results simultaneously published in the New England Journal of Medicine also found that patients taking canagliflozin had a lower risk of hospitalization for heart failure, less loss of kidney function, and a lower risk of progression to albuminuria.3

“People with type 2 diabetes have a substantially increased risk of developing cardiovascular disease, and it’s encouraging that we now have data to show Invokana may help address this challenge,” James F. List, MD, PhD, global therapeutic area head, Cardiovascular and Metabolism, Janssen, said in the company’s statement. “Invokana has shown a clear benefit in reducing cardiovascular risk in adults with type 2 diabetes, and we look forward to working with [the] FDA as it reviews our filing.”1

In March 2013, canagliflozin became the rst sodium glucose cotransporter-2 (SGLT2) inhibitor approved to treat T2D.4 The FDA previously approved a CV indication for empagliflozin, an SGLT2 inhibitor sold as Jardiance by Eli Lilly and Boehringer-Ingelheim.5 SGLT2 inhibitors have a mechanism of action that involves blocking a protein that normally allows the body to reabsorb glucose; instead, the body discharges excess glucose through the urine, offering people with T2D glycemic control, reduced blood pressure, and modest weight loss.

Another agent approved to treat T2D, the glucagonlike peptide-1 receptor agonist liraglutide, sold by Novo Nordisk as Victoza, received a CV Indication in August 2017 based on results that found it reduced the risk of major CV events by 13%.6


1. Janssen submits supplemental new drug application to US FDA seeking new indication for INVOKANA (cana- gliflozin) to reduce the risk of major adverse cardiovascular events (MACE) based on landmark CANVAS program [press release]. Raritan, NJ: Johnson & Johnson; October 2, 2017. submits-supplemental-new-drug-application-snda-to-us-fda-seeking-new-indication-for-invokana-canagliflozin- to-reduce-the-risk-of-major-adverse-cardiovascular-events-mace-based-on-landmark-canvas-program. Accessed October 2, 2017.

2. INVOKANA (canagliflozin) significantly reduces the combined risk of cardiovascular death, myocardial infarction, and stroke in the CANVAS program [press release]. Raritan, NJ, and San Diego, CA: Johnson & Johnson; June 12, 2017. diovascular-death-myocardial-infarction-and-stroke-in-the-canvas-program. Accessed October 2, 2017.

3. Neal B, Perkovic V, Mahaffey KW, et al; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644-657. doi: 10.1056/NEJMoa1611925.

4. US FDA approves INVOKANA (canagliflozin) for the treatment of adults with type 2 diabetes [press release]. Raritan, NJ: Johnson & Johnson; March 29, 2013. gliflozin-for-the-treatment-of-adults-with-type-2-diabetes. Accessed August 21, 2017.

5. US FDA approves Jardiance (empagliflozin) tablets to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease [press release]. Ingelheim, Germany, and Indianapolis, IN: Boehring- er-Ingelheim; December 6, 2016. Accessed October 17, 2017.

6. Victoza (liraglutide) is approved in the US as the only type 2 diabetes treatment to reduce the risk of three major adverse cardiovascular events [press release]. Plainsboro, NJ: Novo Nordisk; August 25, 2017. press.novonordisk-us. com/2017-08-25-Victoza-R-liraglutide-is-approved-in-the-US-as-the-only-type-2-diabetes-treatment-indicated-to- reduce-the-risk-of-three-major-adverse-cardiovascular-events. Accessed October 17, 2017.

FDA Updates Afrezza Label; MannKind to Launch New Talks With Payers


ON SEPTEMBER 29, 2017, the FDA granted MannKind Corp a label update for the inhaled mealtime insulin, Afrezza, which CEO Michael Castagna, PharmD, said will let the company set itself apart from rivals for the first time. Castagna said the change will allow a fresh round of conversations with payers about the drug’s advantages, including lower rates of hypoglycemia.1

The new label, unveiled in an investor call October 2, 2017, states that Afrezza shows up in the bloodstream in approximately 1 minute and reaches its first measurable effects at 12 minutes. More importantly, Castagna pointed to a new table that shows how different doses of Afrezza enter and leave the body quickly, which he said will be crucial in explaining Afrezza’s value to doctors and patients.

“This will allow stronger wording with the sales force,” Castagna said in an interview with Evidence-Based Diabetes ManagementTM (EBDMTM), as he dis- cussed plans for MannKind to revamp discussions with doctors about dosing, especially the problem of underdosing. Castagna has said patients sometimes need more units of Afrezza than the number of insulin units they used in an injected form. The FDA, he said, “wants us to be very specific,” which he described as “a positive surprise.”

The new label also features updated instructions and a new table for titrating the drug, which includes the familiar color-coded insulin cartridges—blue for 4 units of insulin, green for 8 units, and yellow for 12 units—that will help patients new to Afrezza learn what works for them.

Patients who use Afrezza and market watchers who follow MannKind had been waiting to see the language that the FDA would include in the new label to see if it will make a meaningful difference in the way MannKind can position the inhaled insulin with payers and physicians. Afrezza enjoys a loyal core of users who tout its benefits online, and some were urging the FDA to approve an “ultra-fast-acting” designation, which Castagna himself said was a long shot. While the FDA did not add this to the label, Castagna said several key issues were resolved.

Meanwhile, Afrezza will have to compete with Novo Nordisk’s faster-acting mealtime insulin, Fiasp, which received FDA approval for patients with type 1 and type 2 diabetes on the same day as the Afrezza label change.2 Novo Nordisk’s chief medical o cer for diabetes in North America, Todd Hobbs, MD, said in an e-mail that the FDA’s analysis found that Fiasp appeared in the bloodstream in 2.5 minutes.

Castagna said Afrezza acts even more quickly, but the more clinically relevant issue is how quickly it leaves the body—90 minutes for 4 units, and 3 hours for 12 units.

Afrezza’s old label said the drug’s onset was comparable with insulin lispro, which made payers skeptical of its value and created barriers to reimbursement. “We have removed the language that restricted our promotional activity,” Castagna said during a conference call with analysts.

The Afrezza label update is based on data that MannKind presented at the American Diabetes Association Scientific Sessions in June 2016.3 “These data articulate the rapid-acting nature of Afrezza to address post-prandial hyperglycemia, setting it apart from other mealtime options available to help patients maintain greater control over their blood glucose levels,” said Satish Garg, MD, MBBS, DM, of the Barbara Davis Center for Diabetes at the University of Colorado, in a statement.1

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