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

Tolerx Completes Enrollment in Phase-III Otelixizumab Trial

On Jan 7, 2010 Tolerx announced that they had completed enrollment of their DEFEND-1 clinical trial. This is a phase-III study which is randomized, placebo-controlled and includes 240 patients at over 100 sites all over Europe and North America. Because each patient is followed for a year, we can expect results from this study after January 2011.

The study is designed to evaluate whether a single course of otelixizumab, administered to type-1 diabetics during their honeymoon phase, will preserve insulin production.

Otelixizumab targets CD3 receptor on a T cell.  The hope is that it will work in patients with type 1 diabetes who have residual beta cells by blocking autoimmune attack, while helping the "good" regulatory T cells that protect against the "bad" T cells, thus preserving the beta cells' ability to make insulin.

Press Release: http://www.prnewswire.com/news-releases/tolerx-completes-enrollment-in-defend-1-a-phase-3-type-1-diabetes-study-with-otelixizumab-80892467.html
Corporate Description: http://www.tolerx.com/index.php?page=trx4
Trial's Public Web site: www.DefendAgainstDiabetes.com

Diamyd Will Apply for Approval of Type-1 Treatment in 2011

Diamyd has announced that they expect to file the paperwork for market approval of their GAD65 targeted, type-1 treatment in 2011, after they complete the phase-III trials they have ongoing right now.  Obviously, the headline is great, but remember these things:

• No results from their phase-III trials have been released, yet.  They've got two different large phase-III trials going on right now.
  
• Applying for approval is great, but it usually takes a year or two to get it, after you apply.
  
• The current phase-III trials are all for honeymoon only, and so this approval will be for honeymoon only.
  

Even with all that, it would be great news to have something new approved for honeymoon type-1 diabetes. (Even if the short term result is likely to be just "uses less insulin" or "has longer honeymoon".)  Right now, we have nothing like that.  When they publish their phase-III results, we're likely to see how much of a cure this is likely to be, and for how many people.

Also, you might have seen a HULIQ headline "Approval of Diamyd's Diabetes Vaccine Set for 2011".  That's an outright mistake.  They expect to start the approval process in 2011, not finish it then.  The process takes a year or two to complete.

Press release: http://www.tradingmarkets.com/news/stock-alert/dmydf_swedish-diamyd-medical-to-apply-for-diabetes-vaccine-approval-2011-737987.html

Novo Nordisk Receives US Approval for Victoza (liraglutide) for the Treatment of Type 2 Diabetes 

This really isn't type-1 news by itself, but Liraglutide just got FDA approval, and this is the same drug that just started phase-II trials for type-1 diabetics, and that I reported on in January.  So there are now at least two drugs (the other is Byetta) which are approved for type-2s and causes them to generate more insulin.  If a treatment is found that ends the autoimmune attack, then these treatments might be paired with it to create a faster, more complete cure. 

I'm optimistic about this approach, because there are now four drugs in phase-III trials which are targeted at ending the autoimmune attack, and at least two already approved drugs,  another in phase-III trials, and several more in phase-II trials, which increase the insulin supply.  So those two treatments together might represent a relatively quick path to a cure, if they both pan out and work well together.

News Article: http://money.cnn.com/news/newsfeeds/articles/marketwire/0580389.htm

Transition Therapeutics Announces Results of a Phase 2 Study of TT-223 in Type 2 Diabetes Patients
  
At one time it was hoped that TT-223 would help type-1 diabetics regrow their beta cells and generate more of their own insulin.  However current testing is limited to type-2s (as in this trial).  The good news is that it worked for type-2s: the treated group A1C dropped by about 1.13, while the untreated group dropped by only 0.22.  

To me, this suggests that if we are successful at stopping the autoimmune attack, then TT-223 might be helpful in helping to regrow beta cells.  But so far, there is no evidence that TT-223 would be helpful as a single treatment for type-1 diabetics. 


Press release: http://money.cnn.com/news/newsfeeds/articles/globenewswire/182542.htm

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

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: http://www.mchips.com/10_Jan_07_pr.html
News Article: http://www.dotmed.com/news/story/11267/

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: http://www.reuters.com/article/idUSLDE60C0CB20100113?type=swissMktRpt
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00993720
Wikipedia: http://en.wikipedia.org/wiki/Liraglutide

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: http://www.clinicaltrials.gov/ct2/show/NCT00607230

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: http://abcnews.go.com/Business/wireStory?id=9550823

Joshua Levy