Sunday, January 31, 2010

Why Fund J and J / Animas / DexCom Close Loop Trials?

Note: notes like this [d1] are footnotes to more discussion at the bottom of the posting.

Why Fund J and J / Animas / DexCom Closed Loop Trials?

About two weeks ago, JDRF made a big announcement that they were helping to fund research into a closed loop system.  Basically, they are working with Animas (insulin pump manufacturer and division of Johnson and Johnson) who work with DexCom (CGM manufacturer).  JDRF was putting in about 8 million dollars over about 3 years [d0], and was hoping for clinical trials within a year, and FDA approval of a device (although not a full Artificial Pancreas, or AP) within 4 years. 

So the first thing that popped into my head was "why bother?".  By which I meant, why should JDRF bother?  I don't have any problem with JDRF funding commercial companies [d1].  But Johnson and Johnson (especially) is a huge company which could easily fund it's own clinical trials. And it is clear to me (and many others) that closed loop systems were the next big thing in pump technology.

It so happens that last weekend I found myself talking to two guys who know more about corporate research into type-1 than I do, so I asked them this very question: Why should JDRF fund research that Animas was going to do anyway, when Johnson and Johnson had the money to do it?  Their reply was simple:
Animas would never have started the research into a closed loop trial, without the money and public support of JDRF behind it.
My initial reaction was disbelief.  I pointed out that Animas was in the pump business, and the obvious next step in pump development was a closed loop of some kind.  The first company to market a closed loop pump would have a huge advantage over all the other ones.  Of course they would do a closed loop clinical trial.  It had never occurred to me that any of the pump makers would not do a closed loop clinical trial.

But I was wrong.  As I quickly learned by searching through the FDA's clinical trial site.  In fact, Animas was not doing a closed loop trial; None of the big pump companies is currently doing a closed loop trial without JDRF's involvement. [d2]. There were two reasons why not.  The first reason was pretty simple: no pump company knows how to get a closed loop pump through the FDA approval process.  For one thing, no one's ever done it.  For another thing, a closed loop system would involve both a drug and a device.  In the world of the FDA, drugs have one set of rules (and are governed by one part of the agency) while devices have a completely different set of rules (and are governed by a completely different part of the agency) and of course the rules are not coordinated, and the two parts of the agency don't talk to each other much.  So there is a lot of uncertainty about exactly what sort of testing will be required [d3].  How long it will take, and so on.  And uncertainty can be fatal to big company research.  If J and J puts 10 million of their money into it, they will not know if it will take 3 years or 10 years to get through the regulatory process.  And that's a big difference when your stockholders want quarterly profits.

The second reason was simple: if no one does it, then no one has to do it.  This is the downside of capitalism when there are only a small number of companies.  There are only a few companies that market pumps in the US.  And they are all big and highly regulated, and they know pretty much what each other are doing.  So as long as they know that none of their (limited) competition is developing a closed loop system, they don't have to develop one [d4].

So here are some reasons why funding a closed loop clinical trial is a good thing for JDRF to do:

1. It (hopefully) gets one closed loop approved, so people can use it.
I'll put together another post on why closed loop is a good thing, even if it is not a cure.  It's too big a subject to put here, but as a quick summary: an AP is likely to lower many (if not all) of the long term complications of type-1 diabetes.  An AP is likely to be easier to use than a pump, and require much less work on the part of the diabetic.  An AP is likely to prevent the worst single complication of type-1 diabetes: "dead in bed". And an AP may well be required by the eventual cure, because excellent BG control from an AP may be required to regrow beta cells as part of an eventual cure.

2. It might motivate other big pump companies into starting their own clinical trials.
Capitalism is based on competition between companies.  So having JDRF work with one company is likely to motivate other companies to start, hurry, or continue their own research.  So putting money into Animas helps them directly, but also motivates Medtronic and Omnipod to put more of their money into similar research, or to work with JDRF themselves [d5].

3. Once one closed loop system is approved, it will be easier for the others.
One of the problems with the FDA approval process (especially for a combined drug/device), is that the first one through the gate pays a big price both in terms of extra work, but more so in terms of extra uncertainty.  So everyone wants to be second through the process.  Let someone else figure out the rules, and once they are known, then just go through.  Let someone else clear the path.  So if JDRF's money helps clear the path (ie. push Animas through the approval process first) it will end up benefiting Medtronics and Omnipod as well.  And in the end, all type-1 diabetics.

Put another way, consider this: If you have a problem, then you have a problem.  But if you can solve that problem with money, then you merely have an expense.  Companies don't like problems, but understand expenses very well.   Right now, getting FDA approval for an AP is a problem; no one knows the details of how it will be done.  However, if JDRF can spend some money and work with Animas to figure out how to solve that problem, then it will merely be an expense.  And companies know how to deal with expenses.  And an AP will be forthcoming sooner.

More Discussions

[d0] Although a lot of people focus on the money (as I do here), JDRF is bringing more to the table than just money.  They are bringing their previous research (especially previously tested algorithms), and well as a patient recruitment network, etc.

[d1] I think that the goal of JDRF should be to speed development of a cure for type-1 diabetes, and if they think the best way to do that is by funding a researcher at a University, great.  And if they think the best way is to fund a researcher at a company, great.  I don't care where the money goes; I care that it speeds development of a cure.

[d2] This surprised me, but it's true.  Using the FDA's clinical trials database:
There are three studies using Animas, but not a closed loop or feedback study.
There are four studies using Omnipod, but not a single closed loop or feedback study listed.
There are thirty one studies using Metronics, but only one testing a closed loop system and that one is a joint venture of Medtronic and JDRF:
There are thirteen studies covering closed loop devices in diabetes.  One of them is the joint Medtronic/JDRF trial described above.  Of the remaining twelve, all are funded and sponsored by government agencies, hospitals, or universities.  Not one is funded by a company. 

So it is clear to me that the pump companies are not going to fund clinical trials aimed at getting a closed-loop system through the FDA approval process, unless JDRF catalyzes the process.  

[d3] There have been some drug/device combinations improved in the past. For example, drug covered stents.  However it does involve much more uncertainty than either a drug or a device alone.

[d4] This is not a matter of an evil conspiracy, more a case of no one spending money on something they don't have to.   They all think, since none of my competitors is working on a closed loop, then I'll spend my millions on something else.  If one of them does start, then I will start the year after, and still be pretty close to them.  Medical pumps are not a business where being a month (or even half a year) ahead of your competition matters that much, anyway.

[d5] And it is important to remember that JDRF is not playing favorites with companies.  They already have a similar agreement with Metronic, so this one with Animas will be their second, and it shows clearly that JDRF will partner with any company that is moving the research ahead.

This blog posting was unusual in that I asked several people to review it for me and provide suggestions and feedback.  I'd like to thank all of these reviewers.  

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.

Saturday, January 30, 2010

Andromedia's DiaPep 277 Preps for Second Phase-III Trial

I had previously posted an update to Andromedia's DiaPep 227, but that post was based on a misunderstanding of the FDA (and EU) approval process.  This post is a correction to my Monday, November 23, 2009 posting about DiaPep 227.  I'm very sorry for my previous mistake.

Note: Andromedia press releases refer to both DiaPep 227 and DiaPep 277 interchangeably (I think).  This is not a typo.  Their own press release page (link below) contains more than one press release where the headline refers to one number while the text refers to the other.  I'm not sure what  is going on, but I'm assuming that there is only one drug.  I'm using the tag DiaPep 277 from now on in my blog, but in the past I've used both.  It's very confusing! 

Andromedia's DiaPep 277 Preps for Second Phase-III Trial

Andromedia recently announced their plan to move DiaPep 227 into market availability which was approved by EMEA.  EMEA is the European Union's version of the USA's FDA. This will include doing a second phase-III trial after they finish their current phase-III trial (which expected in 2011). This second phase-III study will be large (450 people) and multi-site (100 locations in Europe).

DiaPep 277 is described by Andromedia this way: "a synthetic peptide of 24 amino acids derived from the sequence of the human heat shock protein 60 (Hsp60). The peptide modulates the immune system that leads to autoimmune diabetes by diminishing or blocking the destruction of beta cells by the immune system."  So this treatment is similar to the other ones currently in phase-III trials in that it is designed to preserve beta cells that have not yet been destroyed by the autoimmune attack in honeymoon stage diabetes.

DiaPep 277 has been in a phase-III trial for many years.  It was the first company that I know of to start one for a cure for type-1 diabetes (honeymoon only, unfortunately).  The EMEA (much like the FDA) requires two studies to show safety and effectiveness of new treatments.  Sometimes the two studies are a phase-II study and a phase-III study, but usually, two different phase-III studies are required.  Obviously, pharma companies would prefer to do the two phase-III trials at the same time so they get to market quicker, but sometimes they are done one after the other.  That is the case for DiaPep 277 the first phase-III study will be almost done (or done) by the time the second one starts.

Previously, DiaPep 227 was in the lead in terms of finishing their first phase-III trial.  However, the more important milestone is when they complete their second phase-III trial, and it now looks like they will be behind Diamyd, ToleRx, and MacroGenics.  I think Andromedia is 3-5 years away from market approval and that is assuming that their first phase-III trial has good results, and their second phase-III trial works as they hope.  These are both big assumptions.

Their new clinical trial does not have a clinicaltrials record yet, but it will be for honeymoon diabetes only.

Press release:
All corporate press releases:

Previous blogging on DiaPep277:

Clinical trial sites for the three studies on  DiaPep 277 that I can find:

I would like to thank bellow bravebuddy member Dave for his insight into the FDA approval process, and also for providing me the link to the FDA "guidance document", which you can read here:

Joshua Levy

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.

Tuesday, January 19, 2010

Possible Cures for Type-1 in the News (Jan)

MicroCHIPS Will Start phase-I Trial of new CGM (and gets 16+ million)

For people interested in the artificial pancreas project, MicroCHIPS just got about 16 million dollar investment, and one of the things they will do with that money is start a phase-I study later in 2010 on their CGM technology. Here is their description of why their technology is better than current technology:
MicroCHIPS hopes their product will last months, or even years, and their main innovation is to create the implant with a differently-built sensor. Current devices, Pax says, have a single sensor that can only detect glucose levels until it runs out of the sensing chemical. But the MicroCHIPS device employs a redundant array of sensors, with each one becoming active as needed.
And the part that interests me the most is this:
MicroCHIPS intends to conduct initial clinical testing in 2010 to advance its diabetes program.
Some Discussion

I think it is clear that CGM technology is the weakest component in current artificial pancreas research. However, a CGM technology that lasted 3 months or more in the body would be a huge improvement in this area. So I'm excited by this technology, and am looking forward to seeing how well it works. One of the new funders is Medtronic. Since Medtronic already has cutting edge commercial CGM technology, they are not expecting more of the same: they are expecting better than they have. So I think it is fair to expect that whatever MicroCHIPS is creating, it is a lot better than we have now.

Press Release:
News Article:

Novo starts phase-II Clinical Trial of oral GLP-1

Novo Nordisk (one of the largest pharma companies targeting type-1) is working with Hvidovre University Hospital in Denmark to test an pill version of Victoza (generic: Liraglutide) which is a GLP-1 receptor agonist. They are specifically targeting type-1 diabetics in this study. Technically a phase-II trial (because the drug is already approved), it will enroll about 30 people, and be completed by second half of 2010.

A Little History

Several treatments leveraging GLP-1 have been tried over the years as GLP-1 related drugs help the pancreas generate more insulin. They are usually targeted at type-2 diabetics, who have a lot more useful pancreas to work with. Byetta is the most famous GLP-1 analog used by type-2 diabetics. Of course, the question here is: will it help people with type-1 diabetes?

Some Discussion

This is right on the edge of what I consider a possible "cure". It seems unlikely to me that any treatment that works by causing the pancreas to generate more insulin will -- by itself -- result in a cure for type-1 diabetes. However, I'm reporting on this because it might turn out to be part of a cure. For example, by combining it with Diamyd's, ToleRx's or MacroGenic's treatments (all in phase-III clinical trials, and all of which prevent/weaken the autoimmune attack) .

The injected form of this drug (Victoza) was approved for use in the EU in 2009, and is marketed in at least three countries (UK, Denmark, and Germany). However it has not been approved in the US, because of worries about thyroid tumors. The US FDA review was in April 2009.

If this drug turns out to help type-1 diabetics, then (in addition to Byetta) there are two other similar drugs, each being developed by a different drug company, which may also help type-1 diabetics: albiglutide and taspoglutide.

Press Release:
Clinical Trial Record:

News (but no Announcement) from Faustman

Although Faustman's team has not made an official announcement (at least not one that I've seen), they did reopen enrollment in their phase-I BCG clinical trial, after having closed it last February. Without information on why they did this, there is no way to know if this is good news or bad, or if it will cause a delay in reporting their phase-I results. Although you'd think if it was good news they would have had an announcement.

This is the timeline: In Feburary 2009 they updated their clinical trial record to show that they had finished enrollment in their phase-I trial. In mid 2009 they announced that their results would be published in early 2010, and specifically would be turned over to their internal statistics group in November of 2009. However, in October 2009 they updated their clinical trial record again to show that they were once again enrolling patients in the study. Right now, their web site says specifically they are NOT enrolling new patients, but their Clinical Trials web page says that they ARE enrolling new patients.

What might this mean? The best possible news would be that they are trying to do more with their phase-I trial than originally expected. LCT did this for their trial in Russia. Once it was underway, they updated it to include more people and bigger doses. If the BCG team is trying the same thing, that would be good news.

The worst news would be that they did some early data analysis of their results, and found they did not have statistically significant results. So they added more people to the study in the hopes of getting a statistically significant result. The DiaPep227 guys did this with their phase-III study.

Middle of the road news would be that some of their samples or data got lost, mislabeled, or a patient pulled out at the last minute or something. So they need some more patients to enroll, and might have a delay, but nothing really bad. Something like this happened to Diamyd's phase-II LADA trial.

Clinical Trial Record:

JDRF, J and J's Animas Corp, and DexCom Start Joint AP Project with Clinical Trial this Year

For people interested in the artificial pancreas project, there was a big announce from JDRF of a joint project with Animas (pump makers, and a division of Johnson & Johnson), and DexCom (CGM makers). It's been widely publicized, so I won't go into details. To me, the most interesting part was this:
The first patient testing could begin in less than a year, Kowalski said.
and that is good news, especially since most phase-I AP testing can be done quickly. We should start seeing clinical trial results on this AP combination maybe by end of this year, but more likely sometime next year.

News Article:

Joshua Levy