Sunday, March 8, 2015

Smart Insulin (MK-2640) Starts Clinical Trials

This is a blog posting that I've been waiting four years to write: the start of clinical trials for "Smart Insulin".

First, some general background on "Smart Insulin". The idea here is simple: create a chemical that holds insulin and only releases that insulin when the sugar level in the surrounding region is high. You would not have to measure blood sugar levels or match insulin to food. Instead you would just take this "self-dosing" insulin compound and it would release insulin as needed based on what you ate or did not eat.

"Smart Insulin" was the name of the first strong contender in the field, which was developed by Dr. Zion first at MIT and then at Smart Cells, which was later bought by Merck.  The term is also used generically, to refer to any "self dosing" or "Glucose Responsive Insulin"  (although I'm sure Merck's trademark lawyers would not approve).  No other self dosing insulin is in human trials, but SIA-II, Ins-PBA-F, and Sensulin, are being developed, and those are just the ones that I know about.  Smart Insulin had been tested in mice when it was sold to Merck (in 2010) and so a lot people, myself included, thought it would be in clinical trials quickly.  Obviously, the "quick" part did not happen, but the clinical trial part has started.

Smart Insulin (MK-2640) Starts A Clinical Trial

But the big news is that Smart Insulin has started clinical (human) trials.  In fact, the trial started months ago, in November 2014.   I missed it, mostly because Merck changed the drug's name from "Smart Insulin" to "L-490" to "MK-2640".   The clinical trial was under the name MK-2640, and I missed it.  Luckily Mike Hoskin at DiabetesMine publicized the name change.  You should read his blog for some general background, but notice that MK-2640 (the smart insulin I discuss here) is the second part of the posting:

The trial itself has a fairly complex design.  It's two trials combined into one.  Part 1 is a group of 7 different "panels" (dosing regimens) given to healthy people.  Part 2 is a comparison of regular insulin to MK-2640 in people who have had type-1 diabetes for at least a year.  All of this involves 58 people and is expected to be done by July 2015.  Unfortunately, I cannot tell how many people are doing what, so I don't know if each of the 58 people are doing each dosing regimen, or if the 58 people are divided up between the different doses.  Most of the data they are collecting is "pharmacokinetic" meaning they are measuring how much of the drug is available in the body at any given time.  How quickly it "washes out" of the body and so on.  They will also be looking for adverse events and also patient drop outs caused by adverse events.  For a drug like "smart insulin" where variable dosing is critical to its success, focusing on pharmacokinetics makes a lot of sense to me.

The study is recruiting in Chula Vista, California, USA. Call their toll free number: 1-888-577-8839.

Clinical Trial Record:
ClinicAnnouncement of Merck buying Smart Cells:


My summary is simple: in a few short months, we are going to know a lot more about how "Smart Insulin" works in people, than we know now.

One very good thing about "Smart Insulin", especially when developed by a big pharma company like Merck, is that it can move through the approval process much faster than the other drugs I cover. One of the repeating themes of this blog is that it will take a cure at least 10 years to go through the FDA's approval process, and more years are likely.  That's not rocket science, it is simple math.  The FDA requires three phases, the first phase usually takes a year to recruit the patients and a year to gather the data.  The second and third phases also take a year to recruit the patients, and two years to gather the data, and then there is a year or two for marketing approval, and we are at (2+3+3+2) 10 years.  That assumes that every phase starts the moment the previous phase ends.  In real life there are often months or years of delay between each phase, so in real life these drugs take longer to get approved.

But that is for drugs aimed at curing type-1 diabetes.  For a new insulin, most studies only collect data for three months.  Also, recruiting people is much easier, both because they are adults and because they already are taking insulin, so you're just asking them to take a different insulin.  It's not as scary as something that changes your immune system.   Bottom line is that the phase-I trial is expected to be done in 8 months (recruiting and data collection).  I would expect phase-II and phase-III trials to also be sped up, as compared to cure trials.  The downside is that insulins usually have more than 4 clinical trials before approval, and usually a couple of them are longer than 3 months. But still, I would expect a quicker testing cycle for a new insulin than for a potential cure.

This is a treatment where some people are going to think of it as a cure, and others are going to think of it as a treatment.  That's not an argument I want to spend time on.  I will cover Smart Insulin (at least this first trial) because some people do consider it a cure.  If it is highly effective, then more people might consider it a cure.  Of course, if it doesn't work well or has limitations in how it can be used, then fewer people will consider it a cure.  But I'm happy to cover it for a clinical trial or two.

Joshua Levy 
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.


U can succeed ! said...

Josh, I heard Novo Nordisk is going to start working on their SmartInsulin again. I was at JDRF event in Bethesda MD this past weekend and heard this piece of news. By the way I to was trying to find the clinical trials as well, but could not find the trials until I read the article you read. Thanks for all your work.

Simone wilson said...

I have been T1 for 15 years now with very brittle diabetes. In the UK we are some what behind with medical advances in relation to this disease. I have recently been started on Tresiba and as it is onlynew over here, my gp has never even heard of it. I would like to ask if you know anything about the compatability of novorapid and tresiba? I would also be very interested on helping or taking part in research and medical trials to help other. Thank you, Simone from Northern Ireland

TheScream said...

Josh, thank you so much for all that you do for the T1D community. I share your excitement regarding the promise this "smart insulin" holds. Your blog has helped me immensely in understanding what is important to know regarding the search for a cure. Roseanne