AWIQLI
LAI 287; insulin icodec
Launched in Australia, Canada, the European Union, Mainland China and Japan, AWIQLI® is the first once-weekly, subcutaneously (SC)-administered insulin. This dosing regimen represents a notable advantage over the currently available daily administered basal insulin, which could reduce the dosing burden associated with insulin treatment for type 1 and type 2 diabetes mellitus (T1DM and T2DM).
About AWIQLI
- Novo Nordisk
- Long-acting basal insulin analog
- Once-weekly SC administration to treat T1DM and T2DM
- ~1.8m diagnosed prevalent cases of T1DM in the G7 markets in 2023
- ~10.6m diagnosed cases of T2DM on insulin therapy in 2023
Why is it a drug to watch?
AWIQLI is a once-weekly SC-administered basal insulin analog with a ~8-day half-life for both T1DM and T2DM. In addition, Novo Nordisk developed a mobile app, DoseGuide, to be used with AWIQLI to help find individually optimized insulin doses based on an individual’s earlier doses and blood glucose levels. However, the launch in the United States has been delayed by a CRL from the FDA based on a recommendation from the Endocrinologic and Metabolic Drugs Advisory Committee. The CRL issues requests related to the manufacturing process and the data for T1DM. The company is working closely with the FDA to address the concerns but does not expect to complete the requests during 2024.
Approvals in other countries and regions were supported by data from the phase 3 ONWARDS program, which reported positive efficacy and safety data and hypoglycemia rates that were not statistically significant for AWIQLI compared with other insulin analogs. The trials involving individuals with T2DM encompassed all major groups that are likely to be prescribed AWIQLI:
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ONWARDS 1: insulin-naive adults with T2DM
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AWIQLI (weekly SC) versus insulin glargine (daily SC), both plus background antidiabetic therapy
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Reduction in HbA1c at week 52 from baseline: -1.55% with AWIQLI vs -1.35% with insulin glargine (statistically significant)
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Higher percentage of AWIQLI-treated participants achieved <7% HbA1c target without reporting level 2 or 3 hypoglycemia compared with insulin glargine
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0.30 clinically significant or severe hypoglycemia events per patient-year with AWIQLI vs 0.16 events with insulin glargine (not statistically significant)
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ONWARDS 2: adults with T2DM previously treated with insulin
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AWIQLI (weekly SC) versus insulin degludec (daily SC), both plus background antidiabetic therapy
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Reduction in HbA1c at week 26 from baseline: -0.93% with AWIQLI vs -0.71% with insulin degludec (statistically significant)
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0.73 clinically significant or severe hypoglycemia events per patient-year with AWIQLI vs 0.27 events with insulin degludec (not statistically significant)
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ONWARDS 3: insulin-naive adults with T2DM
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AWIQLI (weekly SC) versus insulin degludec (daily SC), both plus background antidiabetic therapy
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Reduction in HbA1c at week 26 from baseline: -1.57% with AWIQLI vs -1.36% with insulin degludec (statistically significant)
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0.31 clinically significant or severe hypoglycemia events per patient-year with AWIQLI vs 0.15 events with insulin degludec (not statistically significant)
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ONWARDS 4: adults with T2DM on basal-bolus regimen
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AWIQLI (weekly SC) plus insulin aspart (SC 2-4 times daily) versus insulin glargine (daily SC) plus insulin aspart (SC 2-4 times daily)
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Reduction in HbA1c at week 26 from baseline: -1.16% with AWIQLI vs -1.18% with insulin glargine (statistically significant)
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5.64 clinically significant or severe hypoglycemia events per patient-year with AWIQLI vs 5.62 events with insulin glargine (not statistically significant)
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ONWARDS 5: insulin-naive adults with T2DM
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AWIQLI (weekly SC; used with the DoseGuide app) versus insulin glargine (daily SC)
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Reduction in HbA1c at week 52 from baseline: -1.68% with AWIQLI vs -1.31 with insulin glargine (statistically significant)
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0.19 clinically significant or severe hypoglycemia events per patient-year with AWIQLI vs 0.14 events with insulin glargine (not statistically significant)
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ONWARDS 6: adults with T1DM
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AWIQLI (weekly SC) plus insulin aspart (SC 3 times daily at mealtimes) versus insulin degludec (daily SC) plus insulin aspart (SC 3 times daily at mealtimes)
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Reduction in HbA1c at week 26 from baseline: -0.47% with AWIQLI versus -0.51% with insulin degludec
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19.93 clinically significant or severe hypoglycemia events per patient-year with AWIQLI vs 10.37 events with insulin degludec (statistically significant))
In phase 2 trials, AWIQLI had a higher rate of hypoglycemic events compared with insulin glargine; however, the results from these phase 3 trials indicate that, for individuals with T2DM, the number of events were similar to those experienced by the comparator groups.
Review and approval status
April 2023
- BLA submitted: U.S. FDA
- MAA submitted: E.U. EMA
August 2023
- NDA submitted: Japan PMDA
May 2024
- Approved: E.U. EMA
June 2024
- Approved: Japan PMDA, Mainland China NMPA
July 2024
- CRL: U.S. FDA
Actual and expected launch:
- 2024: European Union, Japan, Mainland China (type 2 diabetes only), United Kingdom
- 2025: United States
Patents estimated to expire beginning in 2023
Drug Timeline & Success Rates
Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of October 31, 2024
How will AWIQLI impact the market for T1DM and T2DM?
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The T2DM market is expected to grow due to population demographics such as increasing obesity and cardiovascular risks and an aging population.
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The therapeutic pipeline for T2DM is extremely crowded, with more than 150 drugs in active clinical development, and GLP-1 RAs, including more convenient oral options (e.g., Eli Lilly and Co’s orforglipron), GLP-1 combination therapies (e.g., Novo Nordisk’s IcoSema [insulin icodec + semaglutide] and Novo Nordisk’s CagriSema [cagrilintide + semaglutide]) and other insulin analogs (Eli Lilly and Co’s insulin efsitora alfa ) are dominating the phase 3 pipeline.
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Insulin replacement remains the first-line therapy for T1DM, and AWIQLI is expected to be welcomed for its weekly administration.
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Although the insulin market for both T1DM and T2DM is well established, improved insulin formulations are being investigated.
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AWIQLI is forecast to have first-to-market advantage over Eli Lilly and Co’s once-weekly insulin efsitora alfa.
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Coupled with a growing drug-treated population, AWIQLI is forecast to partially offset the declining sales of long-acting insulins in the major markets, raising it from $17.0bn in 2022 to $23.0bn in 2032. Overall, AWIQLI’s launch will lead to a limited expansion in the insulin market, as most patients who need insulin therapy will already be prescribed daily long-acting insulin.
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However, the availability of nonbranded, biosimilar or interchangeable versions of insulin analogues, such as insulin glargine and insulin degludec; increasing use of insulin pumps; and significant use of GLP-1 RA products further delaying the initiation of insulin therapy in T2DM patients will pose a challenge for AWIQLI.
What gaps in treatment does AWIQLI fill?
The launch of AWIQLI is expected to enhance the quality of life for many patients by reducing the dosing burden associated with insulin injections, though more significantly for patients with T1DM than for patients with T2DM. This could result in better treatment adherence.
What hurdles might it need to overcome to reach blockbuster status?
Barriers to commercial success include the uncertainty about the safety of weekly insulins. This is particularly true for the risk of hypoglycemia, especially for patients with T2DM. In addition, there are concerns about off-schedule administration and a lack of understanding about dose adjustments or dose titration with less frequent weekly dosing. A need also exists for long-term real-world data to increase confidence in the efficacy and safety of weekly insulins. Competition from other therapies could also constrain the market for AWIQLI.
