The Future of Insulin: A List of New Insulin Formulations Under Development

Here you can find a summary of most known insulin formulations under development. We also mention insulins which have recently appeared on the market.

Novo Nordisk

• FIAsp (NN-1218): an ultra-rapid-acting formulation of NovoLog / NovoRapid (insulin aspart). Phase III clinical trials. Can be ready in 2016.
• Tresiba (insulin degludec): ultra-long acting basal insulin, lasts 42+ hours, with flexible time of dosing. Day-to-day variability is 20%. Europe: launched in 2013. USA: approved in Sep 2015. Expected launch: Q1 2016.
• Ryzodeg 70/30 (insulin degludec / insulin aspart): pre-mixed basal-bolus formulation. Launch schedule is the same as for Tresiba.

At EASD 2015, Novo presented materials from clinical trials for these insulin formulations. Novo Nordisk also explores using Victoza for type 1 diabetes (LATIN T1D trial).

From the current R&D pipeline of Novo Nordisk: two more insulin formulations are at a very early phase (Phase I) of clinical trials:

• LAI338 (NN1438) — long-acting basal for daily administration
• LAI287 (NN1436) — long-acting basal intended for once-weekly dosing

Novo Nordisk are interested in bringing more value to their products with new hardware/software technology:

Device Research & Innovation (DRI-US) vision to explore and develop new technology, product ideas, and game-changers that may hold the potential to add value to patients and Novo Nordisk in the future within therapeutic areas covered by Novo Nordisk corporate strategy.

Lilly

• Abasaglar / Basaglar (insulin glargine biosimilar): cheaper analogue of Sanofi’s Lantus. Europe: Approved in Sep 2014. Launched in Aug 2015 (UK). USA: Launch postponed to December 15, 2016 after a patent dispute with Sanofi.
• Ultra-rapid insulin. Phase I clinical trials.

Recently, Lilly has cancelled plans to release their new basal insulin Peglispro because of liver safety issues in clinical trials.

Currently the company runs Phase III clinical trials for a non-insulin drug Empagliflozin (BI10773) for type 1 diabetes. Previously, Lilly collaborated on medications that extend life of beta cells.

Sanofi

• Toujeo (insulin glargine U300, longer-acting version of insulin glargine) — with a goal of converting Lantus users to Toujeo, since the patents for Lantus have expired. Europe: Launched in Aug 2015 (UK). USA: Launched in Apr 2015.
• SAR342434: new insulin lispro biosimilar to Lilly’s HumalogPhase III clinical trials.

Sanofi is also developing LixiLan, a mix of basal insulin with GLP-1, targeted at type 2.

Sanofi and Evotec collaborate on developing beta cell replacement therapies, with a potential deal of €300M.

MannKind

Afrezza: an ultra-rapid-acting inhaled insulin. Previously marketed by Sanofi. Europe: Phase III clinical trials. USA: launched in Jan 2015.

Adocia

• Ultra-rapid acting insulin BioChaperone Lispro — an accelerated version of lispro (Humalog) — in collaboration with Lilly — standard version U100 and concentrated version U200. Clinical trials.
• Rapid acting insulin Hinsbet U100 and U500 — cost-effective rapid insulin and its concentrated version. Clinical trials.
• Mixed insulin BioChaperone Combo — mixed basal/bolus, a combination of Lantus and Humalog, mainly for type 2. Clinical trials.

Source: Adocia website

Biodel

• BIOD-123 — ultra-rapid acting insulin. Phase II clinical trials.
• BIOD-238 and BIOD-250 — ultra-rapid acting insulin. Phase I clinical trials.
• BIOD-531 — concentrated bolus/basal — ultra-rapid acting insulin with basal duration of action — primarily for type 2. Phase I clinical trials.

Source: Slides for investors | Pipeline overview

Biocon

Based in India. Develops cheaper versions of insulins which patents expired.

• Proprietary: new oral insulin IN-105. Phase III clinical trials
• Generic glargine, cheaper version of Lantus (with Mylan). Phase III clinical trials.
• Recombinant human insulin (rh-insulin). Phase III clinical trials.
• Generic lispro, cheaper version of Humalog. Early development, not yet in trials.
• Generic aspart, cheaper version of Novolog. Early development, not yet in trials.

Source: Biocon research pipeline

Merck

• MK-2640 (“Smart Insulin”): Glucose-responsive insulin which starts and stops working depending on glucose levels. Expected launch: 2021 or later.Previously known as “L-490”. Phase I clinical trials.
• insulin glargine biosimilar (generic Lantus). Phase III clinical trials.

Other companies

• Generex: insulin oral, insulin buccal (Oral-lyn, Oralgen) launched in United Arab Emirates and India, awaiting approval or Phase III trials in several other markets.
• Halozyme: ultra-rapid acting: Insulin-PH20 & Analog-PH20. Phase II clinical trials.
• Oramed: insulin oral. Phase II clinical trials for T1D in Israel. An orally ingestible insulin capsule.

Open source insulin

As a part of do-it-yourself movement, there is an initiative to create an open-source protocol for insulin.

the Open Insulin project team is made up of roughly 50 self-described “hackers and tinkerers” who proudly point out they are all “bio-curious” — with a mix of genetic engineering, software, biochemistry and biotech experience. [..]
“People across the world are going without insulin because it’s so expensive, and we need to do something about that,” Anthony says. “Maybe someday, what we’re doing here could lead to a do-it-yourself insulin factory.”
— Biohackers Creating Open-Source Insulin

Summary

Market trends:

• new ultra-rapid acting insulins to replace Humalog and Novolog (patents expired), important for pump users and real-time artificial pancreas;
• new attempts to create oral insulin, as ingestible capsules;
• cheaper versions of Lantus and other insulins with expired patents;
• new basal insulins with longer action, more important for type 2 diabetes;
• mixed formulations for type 2 market: mixed basal/bolus and other mixed medications;
• exploration of non-insulin drugs for glucose control in type 1 diabetes.

DISCUSSION

Reddit: The future of insulin: A list of new insulin formulations under development.

Reddit: Anyone heard of this new insulin in development? Its from MERCK, the MK-2640 “Smart Insulin”

Q&A

Is Humalog involved in these or other trials?

Sometimes they compare new insulins to Humalog.

Example 1: “BioChaperone Lispro is 35% faster than Humalog.”

Comparison: BioChaperone Lispro vs. Humalog

Example 2: “Afrezza absorbs faster than Humalog, but 8 units of Afrezza have less potency than 8 units of Humalog.”

Comparison: Afrezza vs. Humalog

COMMENTS

Aizad Sayid, 2016/06/28 at 11:20 pm:

The only truly breakthrough Diabetes drug would be the one that varies its intensity with BG levels. I am also amazed that U-500 form of synthetic insulin is not readily available and no major drug company has marketed this product. I am a type 2 diabetic, and one of the millions dealing with insulin resistance, and injecting such a large volume of insulin every day is quite painful at times.

Olga, 2016/10/14 at 10:52 am:

There are research projects about glucose-responsive insulin (“smart insulin”), but there’s nothing market-ready.

As of U-500 insulin, I am sure it’s only a matter of time. Humulin R U-500 is already marketed. Other U-500 formulations are in development. There was a reported problem with higher hypoglycemia risk for U-500R, so more studies were needed.

Chris, 2016/10/17 at 5:12 pm:

I am a Type I diabetic (40 years). It would be wonderful if insulin prices could come down. I have a high deductible insurance plan, and don’t make a million dollars year…so cost is very important for me to survive. I use Novolin N vials (through Walmart) which are only about $25.00 dollars a vial. But, Humalog is now costing me $293.00/vial each month. is there an equivalent rapid acting insulin that is cheap?

Olga, 2016/10/17 at 5:45 pm:

Equivalent rapid-acting insulins are Novolog and Apidra. They are all modern rapid-acting insulins, with similar time of action, but I know that people may prefer one insulin over another. Unfortunately Walmart doesn’t have a rapid-acting insulin in their portfolio. But I heard that Apidra could cost around $160 at Walgreens. Probably it would make sense to compare prices at different pharmacies. Have you already checked out “Lilly Savings Card” and “Lilly Cares Patient Assistance Programs”? There is also inhaled insulin Afrezza which is marketed as “ultra-rapid acting”, but I’m not sure about their pricing.