Study 171 Shows Hypoglycemia is Reduced with Use of Afrezza®

[kite]

WESTLAKE VILLAGE, Calif., Dec. 20, 2019 (GLOBE NEWSWIRE) -- MannKind Corporation (NASDAQ: MNKD) announced today that Hypoglycemia is reduced with use of inhaled Technosphere® Insulin relative to insulin aspart in type 1 diabetes mellitus has been published online in DIABETICMedicine.

This post-hoc analysis was designed to further evaluate the risk of hypoglycemia observed in adults with type 1 diabetes who were treated with inhaled Technosphere Insulin (Afrezza®) or subcutaneous insulin aspart. Specifically, the research controlled for the level of any HbA1c achieved on the incidence rates of hypoglycemia (low levels of sugar in the blood) in 375 adults with type 1 diabetes. The data demonstrated the following:

Participants treated with Afrezza experienced statistically significantly lower rates of level 1 (blood glucose ≤ 3.9 mmol/L or 70 mg/dL) and level 2 (blood glucose ≤ 3.0 mmol/L or 54 mg/dL) hypoglycemic events. There was also a trend towards lower rates of level 3 hypoglycemia (requiring external assistance for recovery) than participants treated with insulin aspart.

The lower rate of hypoglycemia with Afrezza was observed across the range of end-of-treatment A1c levels.

Due to its unique pharmacokinetic/pharmacodynamic profile, Afrezza was associated with higher rates of hypoglycemia 30–60 minutes after meals but significantly lower rates 2–6 hours after meals.

These data indicate that participants using Afrezza experienced clinically non-inferior glycemic control and lower hypoglycemia rates across a range of A1c levels compared with participants receiving insulin aspart.

Hypoglycemia and fear of hypoglycemia are barriers to effective insulin therapy and may prevent people with diabetes from achieving glycemic targets. Potential risks associated with hypoglycemia include, but are not limited to, treatment costs, limiting the individual patient’s capacity to intensify diabetes control, individual patient rates of productivity, as well as many other debilitating effects.

The published research can be found online at onlinelibrary.wiley.com/doi/abs/10.1111/dme.14202


www.globenewswire.com/news-release/2019/12/20/1963517/0/en/Study-171-Shows-Hypoglycemia-is-Reduced-with-Use-of-Afrezza-Relative-to-Insulin-Aspart-in-Type-1-Diabetes.html

[tw12]

From the Diabetic Medicine posting this morning:

What's new?

Hypoglycaemia and fear of hypoglycaemia are barriers to effective insulin therapy and may prevent people with diabetes from achieving glycaemic targets.

Administration of inhaled Technosphere® Insulin at mealtime provides comparable glycaemic control and lower rates of hypoglycaemia across a range of HbA1c levels compared with subcutaneous insulin aspart in people with type 1 diabetes mellitus.

The ultra‐rapid time‐action profile of Technosphere Insulin offers the flexibility to dose at the beginning of or 20 min after starting a meal, and allows for the convenience of between‐meal dosing with a lower risk of hypoglycaemic events compared with subcutaneous rapid‐acting insulin analogues.

[bababooey]

So this the same study from 2015 right? Looks like they made a PR because it was published on an online journal? I am really confused guys. This doesn't deserve a PR imo. I sure hope to god this isn't throwing a soft ball before announcing bad news such as another dilution

[lennymnkd]

Mike said the focus will be more on type 1 maybe this is part of it .

[porkini]

Dec 20, 2019 9:31:40 GMT -5 bababooey said:

So this the same study from 2015 right? Looks like they made a PR because it was published on an online journal? I am really confused guys. This doesn't deserve a PR imo. I sure hope to god this isn't throwing a soft ball before announcing bad news such as another dilution

Multiple references appear to be more current than 2015. Realizing that some of those references are for package inserts, my thinking is that this publication emphasizes how the more things change, the more they stay the same (interpret that as you may).

[sayhey24]

This study aka Affinity-1 was the basis for the 13-1 Adcom vote to approve. Here is the original PR from 2013.
investors.mannkindcorp.com/news-releases/news-release-details/mannkind-announces-positive-clinical-data-afrezza-both-affinity

The primary focus was A1c reduction. All insulin reduces A1c. The more insulin the greater the reduction. The problem is not getting a hypo. afrezza in 171 was non-inferior in A1c but superior in hypos. However, the lower hypos were not discussed much back in in the day.

Dr. Kendall is now laying the foundation for the "ultra acting" class showing afrezza is a game changer because of the biggest issue insulin has - hypoglycemia.

[sayhey24]

What was also hard to show back in the day was the value afrezza has in stopping the post meal spike and keeping prandial BG flat. CGMs now make it obvious and demonstrate the value of second dosing through pictures. There is no more hiding behind an average point in time A1c.

[lennymnkd]

That's what make this whole thing frustrating. A real live truth detector ... CGM / and we can't win.

[sayhey24]

Lenny - when I first met Mike at the 2016 annual meeting I told him afrezza was doomed without CGMs. He really had little idea what I was talking about as I was talking CGMs, the cloud and connected care. He really thought I was a bit crazy. That was only 3 1/2 years ago.

Now Mike is talking CGMs, the cloud and connected care and I believe Dr. Kenndal is making forward progress. Granted, this whole thing has taken a lot longer than any of us would have liked but IMO we are starting to pick up momentum.

[mnholdem]

Dec 20, 2019 10:32:12 GMT -5 sayhey24 said:

This study aka Affinity-1 was the basis for the 13-1 Adcom vote to approve. Here is the original PR from 2013.
investors.mannkindcorp.com/news-releases/news-release-details/mannkind-announces-positive-clinical-data-afrezza-both-affinity

The primary focus was A1c reduction. All insulin reduces A1c. The more insulin the greater the reduction. The problem is not getting a hypo. afrezza in 171 was non-inferior in A1c but superior in hypos. However, the lower hypos were not discussed much back in in the day.

Dr. Kendall is now laying the foundation for the "ultra acting" class showing afrezza is a game changer because of the biggest issue insulin has - hypoglycemia.

CMO David Kendall made a point last year when he stated that data from more than ten years of trials and studies remained unpublished. MannKind never had a Chief Medical Officer with the credentials and experience to make sense of all that data until they hired Dr. Kendall, one of the medical industry’s leading expert in diabetes research.

I was annoyed by the unexplained delay, but I am delighted that this information is finally being disseminated.

[sayhey24]

Until very recently its been all about A1c. I am listening to a Trulicity commercial right now and it starts off with A1c. Until CGMs the community was not ready to go past that.

When we are talking about stopping the post meal spike and keeping the PWD flat after eating we are talking insulin. SGLT2s, GLP1 and the rest are not going to do it. Before CGMs few knew what was going on. Now its pretty hard to ignore the pictures.

Now the goal is to change the perception that all insulin is dangerous. That is the mission Dr. Kendall is on. Part of the challenge is what Shawn Flynn sees with his basal. Its easier with T2s not on other meds but with the T1s taking other subqs things are not always perfect. Its better, alot better but as Al called it "a bit more tricky".

[brianrocco]

A stupid question from a non-diabetic: Although this study showed almost a 50% reduction in hypoglycemic events using Afrezza as opposed to asparte insulin , there remained a worrying incidence of hypoglycemic events -- more than 1 per participant -week on average. Does a more recent study using strategies of multi-dosing during meals in conjunction with a CGM show significant further reduction in incidence of hypoglycemic events?

Many thanks.

[agedhippie]

Dec 20, 2019 9:31:40 GMT -5 bababooey said:

So this the same study from 2015 right? Looks like they made a PR because it was published on an online journal? I am really confused guys. This doesn't deserve a PR imo. I sure hope to god this isn't throwing a soft ball before announcing bad news such as another dilution

Diabetes Medicine is the house journal of Diabetes UK, the UK equivalent of the ADA. It's online in the same sense that, like NEJM, BMJ, Diabetes Care, and practically every other medical journal is these days - that they publish an online copy of the print version.

[mnholdem]

Dec 21, 2019 9:23:43 GMT -5 brianrocco said:

A stupid question from a non-diabetic: Although this study showed almost a 50% reduction in hypoglycemic events using Afrezza as opposed to asparte insulin , there remained a worrying incidence of hypoglycemic events -- more than 1 per participant -week on average. Does a more recent study using strategies of multi-dosing during meals in conjunction with a CGM show significant further reduction in incidence of hypoglycemic events?

Many thanks.

As I recall, Alfred Mann once pointed out that many of the earlier trial doctors were dosing too early before meals, which caused more hypo events than was expected.

[agedhippie]

Dec 21, 2019 9:23:43 GMT -5 brianrocco said:

A stupid question from a non-diabetic: Although this study showed almost a 50% reduction in hypoglycemic events using Afrezza as opposed to asparte insulin , there remained a worrying incidence of hypoglycemic events -- more than 1 per participant -week on average. Does a more recent study using strategies of multi-dosing during meals in conjunction with a CGM show significant further reduction in incidence of hypoglycemic events?

Many thanks.

The STAT study is probably what you are after - www.liebertpub.com/doi/10.1089/dia.2018.0200

At the end of the day Afrezza is still insulin, and getting the dose or timing wrong can still get you a hypo even if the margin for error is greater on the dosing.