LCT has (finally) gotten government approval to start a phase-I human trial of their DiabeCell product. This is an encapsulated pig pancreas treatment for type-1 diabetes. The New Zealand government has promised this approval months ago, after years of dragging their feet, and now has finally made good on it's commitment. However one important limitation has been put on the trial: only so-called "brittle" type-1 diabetics can be enrolled.
Although LCT is downplaying the importance of this limitation, it has the potential to delay the end of the trial still further. Previously, almost any type-1 diabetic could take part in the trial, so it was easy to find patients to participate. But now, only "brittle" type-1s can participate and that will doubtless cause delays in recruiting participants. "Brittle" diabetics are those diabetics who's BG can drop very quickly. These are the guys who can pass out while driving, or regularly end up in the hospital after collapsing.
Limiting the study to brittle diabetics should make for better results, because these guys have the worst control, and therefore should see the biggest improvements. So from that point of view, it is a good thing. However, it will also slow the trial and delay completion, which is not good.
I view limiting the study to brittle diabetics as 100% political ass-covering (please excuse the language). I think the New Zealand minister of health had delayed so long, that he simply could not just say "yes", because he could have (and should have) done that months ago. So by forcing a change -- any change -- he can claim that the delay was for a good reason. But it's a pointless restriction, and totally unjustified. Pancreatic transplants, which have huge side effects are limited to brittle diabetics, but these encapsulated transplants have basically no side effects, when compared with whole organ transplants. Putting the same restrictions on the patients for one as for the other is really a farce.
LCT has previously started a phase-I human trial in Russia, and so far, 7 people have been treated as part of that study. Some have been treated more than once, and data has been publicized. Some patients in that study were insulin free for a period of a few weeks. I felt the overall results suggested that the treatment did work, but that the implants stopped working just a few months after they were implanted. Others were a lot more excited about these results than I was.
I can not find a USA Clinical Trial record for this work (probably because it is being done in New Zealand), and the information I've read in the press about the experiment make it sound like a repeat of the Russian human trial. Eight patients, for example. Hopefully they will at least use larger doses, so they can learn something new that way.
While getting permission to run this trial is a step forward, I'm not exactly sure how it leads to general availability of the treatment. It is the second phase-I study started, but no phase-II study is planned (that I know of). In the past LCT had talked about a phase-II study in Denver, but when the economy got into trouble a few months ago, they stopped talking about that, and laid off at least one of the key people involved in it. So overall, I'm happy to see them do another study, but I'm also waiting for some information on how they plan to get from phase-I trials (which they have done and are doing) to general availability of the treatment.
Joshua Levy
Thursday, June 25, 2009
Tuesday, June 23, 2009
Update on Andromedia's DiaPep227: Money to Market
You might have seen this recently headline from Reuters:
Andromeda says Teva to market diabetes treatment
This headline is quite misleading. What has actually happened is this: "Teva had decided to exercise its option to complete a $13.5 million investment to market Andromeda's treatment for Type I diabetes." This is an announcement about money, not about the availability of a treatment for type-1 diabetes.
Andromeda's treatment, called DiaPep 277 is a a "heat shock protein". This is a protein that is generated naturally by the body when stressed, and is known to help modulate immune response. The following article:
http://www.diabetesincontrol.com/results.php?storyarticle=793
contains a good overview of heat shock proteins, and how DiaPep 277 is supposed to work. But remember that the clinical trial discussed there are 7 years old at this point.
It is in the middle of a 5 year phase-III human trial, starting in June 2005 and ending in June 2011. I believe it was the earliest possible type-1 cure to go into phase-III human trials (the last phase before marketing approval). The early results were not very promising, but they added more people to the trial, and changed the way they analyzed the data, and are hoping for good results. So far, I have not seen any good news type results from this study, but Andromeda seems very positive, and Teva has put in over US$ 15 million over the last year, so they think that something is there. I just do not see it myself.
Press coverage:
http://www.reuters.com/article/rbssHealthcareNews/idUSLM39121220090622
Clinical Trial record for this study:
http://www.clinicaltrials.gov/ct2/show/NCT00615264
More information here:
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#Diapep277orhsp60byAndromeda
http://cureresearch4type1diabetes.blogspot.com/search/label/Andromeda
Joshua Levy
Andromeda says Teva to market diabetes treatment
This headline is quite misleading. What has actually happened is this: "Teva had decided to exercise its option to complete a $13.5 million investment to market Andromeda's treatment for Type I diabetes." This is an announcement about money, not about the availability of a treatment for type-1 diabetes.
Andromeda's treatment, called DiaPep 277 is a a "heat shock protein". This is a protein that is generated naturally by the body when stressed, and is known to help modulate immune response. The following article:
http://www.diabetesincontrol.com/results.php?storyarticle=793
contains a good overview of heat shock proteins, and how DiaPep 277 is supposed to work. But remember that the clinical trial discussed there are 7 years old at this point.
It is in the middle of a 5 year phase-III human trial, starting in June 2005 and ending in June 2011. I believe it was the earliest possible type-1 cure to go into phase-III human trials (the last phase before marketing approval). The early results were not very promising, but they added more people to the trial, and changed the way they analyzed the data, and are hoping for good results. So far, I have not seen any good news type results from this study, but Andromeda seems very positive, and Teva has put in over US$ 15 million over the last year, so they think that something is there. I just do not see it myself.
Press coverage:
http://www.reuters.com/article/rbssHealthcareNews/idUSLM39121220090622
Clinical Trial record for this study:
http://www.clinicaltrials.gov/ct2/show/NCT00615264
More information here:
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#Diapep277orhsp60byAndromeda
http://cureresearch4type1diabetes.blogspot.com/search/label/Andromeda
Joshua Levy
Saturday, June 20, 2009
News from MacroGenics on Teplizumab
Two pieces of news from MacroGenics:
First, their phase-II human trial of teplizumab (called PROTEGE) is fully enrolled.
Second, they are starting a follow on phase-III study called PROTEGE ENCORE.
Teplizumab is a "humanized monoclonal antibody" which targets the CD3 part of the immune system in order to lower (or stop) the body's autoimmune response. This drug tries to prevent type-1, or lessen it's severity, by "turning down" the immune system's attack on the body's own pancreas cells. This basic approach has resulted in treatments (but not cures) for other autoimmune diseases. It does carry the risk that the body's immune system will not properly attack a real threat.
Fully enrolling a study (especially one this large: 530 people) is important because the major reason that studies are delayed, is trouble enrolling people in them. Especially a study like this where only "honeymoon" diabetics can participate, getting 530 often takes longer than planned. But once it is fully enrolled, that source of delay is removed.
The new study is a sign that MacroGenics is looking to productize this drug. The new study is focused on "clinical responses". That's research-speak to mean "does it help patients" or "do real people benefit in a useful way from this treatment". This is the kind of trial you do just prior to putting it on the market. The new study is 400 people and is scheduled from June 2009 to June 2012.
There is also a third PROTEGE trial which is ongoing, called PROTEGE Extension, which follows patients from the PROTEGE trial for an extended length of time.
If you view the path to a cure as a race, then with this announcement MacroGenics has pulled even with ToleRx which also has a CD3 targeted humanized monoclonal antibody in phase-III human trials. (That's the DEFEND trial of Otelixizumab.) It is interesting, to me at least, to see the dance of small companies and big companies. The PROTEGE trial is sponsored by MacroGenics. The PROTEGE Extended trial by MacroGenics / Eli Lilly, and the PROTEGE Encore trial by Eli Lilly, so you can see how Eli Lilly taking over the Teplizumab treatment from MacroGenics. Similarly, ToleRx has a partnership with GlaxoSmithKline for their Otelixizumab treatment.
(Note: MacroGenics/Eli Lilly calls PROTEGE a "phase-II/III trial", and the Encore trial a phase-III. But I considered PROTEGE a phase-II and Encore a phase-III.)
You can read more about it here:
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#MacroGenics
(although I really need to update this)
Read the press release here:
http://sev.prnewswire.com/health-care-hospitals/20090616/PH3265516062009-1.html
The web page home of this trial is here:
http://www.protegediabetes.org/
Here are the US Clinical Trial entries for all three studies:
http://www.clinicaltrials.gov/ct2/show/NCT00385697 (Protege)
http://www.clinicaltrials.gov/ct2/show/NCT00870818 (Extension)
http://www.clinicaltrials.gov/ct2/show/NCT00920582 (Encore)
Joshua Levy
First, their phase-II human trial of teplizumab (called PROTEGE) is fully enrolled.
Second, they are starting a follow on phase-III study called PROTEGE ENCORE.
Teplizumab is a "humanized monoclonal antibody" which targets the CD3 part of the immune system in order to lower (or stop) the body's autoimmune response. This drug tries to prevent type-1, or lessen it's severity, by "turning down" the immune system's attack on the body's own pancreas cells. This basic approach has resulted in treatments (but not cures) for other autoimmune diseases. It does carry the risk that the body's immune system will not properly attack a real threat.
Fully enrolling a study (especially one this large: 530 people) is important because the major reason that studies are delayed, is trouble enrolling people in them. Especially a study like this where only "honeymoon" diabetics can participate, getting 530 often takes longer than planned. But once it is fully enrolled, that source of delay is removed.
The new study is a sign that MacroGenics is looking to productize this drug. The new study is focused on "clinical responses". That's research-speak to mean "does it help patients" or "do real people benefit in a useful way from this treatment". This is the kind of trial you do just prior to putting it on the market. The new study is 400 people and is scheduled from June 2009 to June 2012.
There is also a third PROTEGE trial which is ongoing, called PROTEGE Extension, which follows patients from the PROTEGE trial for an extended length of time.
If you view the path to a cure as a race, then with this announcement MacroGenics has pulled even with ToleRx which also has a CD3 targeted humanized monoclonal antibody in phase-III human trials. (That's the DEFEND trial of Otelixizumab.) It is interesting, to me at least, to see the dance of small companies and big companies. The PROTEGE trial is sponsored by MacroGenics. The PROTEGE Extended trial by MacroGenics / Eli Lilly, and the PROTEGE Encore trial by Eli Lilly, so you can see how Eli Lilly taking over the Teplizumab treatment from MacroGenics. Similarly, ToleRx has a partnership with GlaxoSmithKline for their Otelixizumab treatment.
(Note: MacroGenics/Eli Lilly calls PROTEGE a "phase-II/III trial", and the Encore trial a phase-III. But I considered PROTEGE a phase-II and Encore a phase-III.)
You can read more about it here:
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#MacroGenics
(although I really need to update this)
Read the press release here:
http://sev.prnewswire.com/health-care-hospitals/20090616/PH3265516062009-1.html
The web page home of this trial is here:
http://www.protegediabetes.org/
Here are the US Clinical Trial entries for all three studies:
http://www.clinicaltrials.gov/ct2/show/NCT00385697 (Protege)
http://www.clinicaltrials.gov/ct2/show/NCT00870818 (Extension)
http://www.clinicaltrials.gov/ct2/show/NCT00920582 (Encore)
Joshua Levy
Friday, May 29, 2009
Exsulin: New Phase-I Research Almost Ready to Start (for Non-Honeymoon Type-1 Diabetes)
The Exsulin company is hoping to start Phase-I human trials in June 2009 (so right soon now). They are testing a new formulation of INGAP called Exsulin, a drug designed to regrow beta cells in the pancreas.
Their Phase-I clinical trial is small, short, and open to people who have had type-1 diabetes for more than 2 years, so we should have some results soon. It is a three group design. One group gets nothing, one gets a full dose, the other gets a half dose. They are checking for all the right stuff: C-peptide, fasting glucagon, fasting glucose, total daily insulin dose, and HbA1c. They are using two sites Montreal and Rochester.
This is described on their web site:
http://www.exsulin.com/underway.html
INGAP (now renamed Exsulin) has a 12 year history of research. NOD mice trials worked well, but human trials didn't show much success (sound familiar?) The phase-I study is described here: http://www.clinicaltrials.gov/ct2/show/NCT00034255. The phase-II study is described here: http://www.clinicaltrials.gov/ct2/show/NCT00071409. It was funded by Proctor and Gamble but the results were not good enough to move forward.
The original developers of INGAP got back rights to it after P&G didn't like the phase-II results. Their analysis of the results convinced them that INGAP was helping grow new beta cells, but that those new cells were being killed off too quickly to help the patient. (Maybe because of the body's immune system, or maybe because of inflammation, or maybe for some other reason.) So it is natural for them to pair Exsulin with another drug to treat the other problem, and see if both together can cure type-1 diabetes. But the research they are starting now is just Exsulin, not paired with anything.
Joshua Levy
Their Phase-I clinical trial is small, short, and open to people who have had type-1 diabetes for more than 2 years, so we should have some results soon. It is a three group design. One group gets nothing, one gets a full dose, the other gets a half dose. They are checking for all the right stuff: C-peptide, fasting glucagon, fasting glucose, total daily insulin dose, and HbA1c. They are using two sites Montreal and Rochester.
This is described on their web site:
http://www.exsulin.com/underway.html
INGAP (now renamed Exsulin) has a 12 year history of research. NOD mice trials worked well, but human trials didn't show much success (sound familiar?) The phase-I study is described here: http://www.clinicaltrials.gov/ct2/show/NCT00034255. The phase-II study is described here: http://www.clinicaltrials.gov/ct2/show/NCT00071409. It was funded by Proctor and Gamble but the results were not good enough to move forward.
The original developers of INGAP got back rights to it after P&G didn't like the phase-II results. Their analysis of the results convinced them that INGAP was helping grow new beta cells, but that those new cells were being killed off too quickly to help the patient. (Maybe because of the body's immune system, or maybe because of inflammation, or maybe for some other reason.) So it is natural for them to pair Exsulin with another drug to treat the other problem, and see if both together can cure type-1 diabetes. But the research they are starting now is just Exsulin, not paired with anything.
Joshua Levy
Wednesday, May 27, 2009
DiaKine starts Phase-I clinical trials on Lisofylline (LSF)
DiaKine is about to start it's first clinical trial in a research program aimed at curing type-1 diabetes. Their treatment is Lisofylline (LSF), an anti-inflammatory drug that (in NOD mice) has prevented type-1 diabetes and (when given with exendin-4) cured existing type-1 diabetes.
Previously (in May 2008) DiaKine has formed a joint project with Kinexum Metabolics, to run a human trial (phase-II) using both of their drugs together (LSF and INGAP). The combination had already given good results in NOD mice. That trial was supposed to start in "late 2008". Kinexum Metabolics has since changed it's name to Exsulin (not INsulin, but EXsulin. Get it?) I can't find any record of the LSF+INGAP trial starting, but each company is testing it's own stuff seperately, so maybe after that, they'll test them together. I know a lot of people are interested in an anti-inflammatory and a beta-cell growing combination therapy, and obviously these two companies are interested in that, also. In any case, this trial is LSF only, not the combo they talked about earlier.
The current trial involves 8 people, and is supposed to start in May 2009 and be done by December 2009.
This research is being done in New Jersey.
You can read a news article here:
http://www.earthtimes.org/articles/show/diakine-therapeutics-diabetes-immune-modulator-drug-set-for-human-clinical-trial,821004.shtml
The US FDA's clinical trial record is here:
http://clinicaltrials.gov/ct2/show/NCT00896077
And the official press release is here (and is better than most):
http://www.diakine.com/assets/news20090512.pdf
The press release talking about LSF+INGAP together is here:
http://www.diakine.com/assets/news20080506.pdf
I want to thank the Wainscoat family for bringing this to my attention.
Joshua Levy
Previously (in May 2008) DiaKine has formed a joint project with Kinexum Metabolics, to run a human trial (phase-II) using both of their drugs together (LSF and INGAP). The combination had already given good results in NOD mice. That trial was supposed to start in "late 2008". Kinexum Metabolics has since changed it's name to Exsulin (not INsulin, but EXsulin. Get it?) I can't find any record of the LSF+INGAP trial starting, but each company is testing it's own stuff seperately, so maybe after that, they'll test them together. I know a lot of people are interested in an anti-inflammatory and a beta-cell growing combination therapy, and obviously these two companies are interested in that, also. In any case, this trial is LSF only, not the combo they talked about earlier.
The current trial involves 8 people, and is supposed to start in May 2009 and be done by December 2009.
This research is being done in New Jersey.
You can read a news article here:
http://www.earthtimes.org/articles/show/diakine-therapeutics-diabetes-immune-modulator-drug-set-for-human-clinical-trial,821004.shtml
The US FDA's clinical trial record is here:
http://clinicaltrials.gov/ct2/show/NCT00896077
And the official press release is here (and is better than most):
http://www.diakine.com/assets/news20090512.pdf
The press release talking about LSF+INGAP together is here:
http://www.diakine.com/assets/news20080506.pdf
I want to thank the Wainscoat family for bringing this to my attention.
Joshua Levy
Monday, May 25, 2009
NovImmune to enter Phase-II with NI-0401 (Another CD3 targeted drug)
It looks like NovImmune (a Swiss company) will start phase-II trials of NI-0401, a CD3 targeted drug "this quarter" and hope to have results in 2011 "at the earliest". The trial is expected to be multi-site and have between 100 and 200 patients enrolled, making it pretty big for a phase-II. The drug has already completed a phase-I clinical trial for Crohn's disease, another diseases where the immune system attacks it's own body. I can't find any record of a phase-I trial for this drug in type-1 diabetes, so I assume they are using their safety data from the Crohn's testing to justify a phase-II trial for type-1 without a separate phase-I.
News article is here:
http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=50851
If treatments targeting CD3 sound familiar, that is not surprising. There are two other CD3 targeted treatments already in human trials. ToleRx's Otelixizumab (in phase-III trials now), and MacroGenics's Teplizumab (in phase-II trials now).
More information on ToleRx (Otelixizumab previously TRX4) :
http://cureresearch4type1diabetes.blogspot.com/search/label/Otelixizumab
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#TRX4alsoknownasChAglyCD3byToleRx
More information on MacroGenics (Teplizumab):
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#MacroGenics
Joshua Levy
News article is here:
http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=50851
If treatments targeting CD3 sound familiar, that is not surprising. There are two other CD3 targeted treatments already in human trials. ToleRx's Otelixizumab (in phase-III trials now), and MacroGenics's Teplizumab (in phase-II trials now).
More information on ToleRx (Otelixizumab previously TRX4) :
http://cureresearch4type1diabetes.blogspot.com/search/label/Otelixizumab
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#TRX4alsoknownasChAglyCD3byToleRx
More information on MacroGenics (Teplizumab):
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#MacroGenics
Joshua Levy
Thursday, May 21, 2009
Haller Cord Blood trial, results from Phase-I and Starting Phase-II
Haller at University of Florida is running a research program to transfuse into honeymoon diabetics their own (previously frozen) umbilical cord blood. Umbilical cord contains stem cells and also a lot of a specific type of T-cell (part of the immune system) called T-regulators. These cells help to regulate the immune system, and since type-1 diabetes is caused by a lack of immune regulation, this seems like a reasonable thing to try. Especially since more and more people are "banking" their children's umbilical cords at birth. The Phase-I study was focused on two possible paths to a cure: adult stem cells would migrate to the pancreas and help grow new beta cells, and/or T-regulators would help suppress the bad immune response. It appears that the adult stem cells path did not pan out, and the phase-II trial only discusses the T-reg mechanism, and not the adult stem cell mechanism.
So the basic status is that Haller has completed a phase-I trial, and gotten good results, and has started a phase-II trial.
The Phase-I Trial
It is supposed to involve 23 patients and run from April 2005 to July 2010, however the data I've seen covered 8 patients and was published in June 2007, so it is an interim result.
That said, the results were good: a few months after the transfusion, the treated kids had an average A1C 1 point lower than untreated (7 compared to 8), they used about 2/3 as much insulin per kg of body weight as the untreated patients, and they generated more C-peptide in response to food (meaning they generated more of their own insulin).
For the phase-I trial:
http://cordblood.cryosite.com/UserFiles/File/Cord%20Blood%20and%20Diabetes.pdf Nice summary
http://www.ncbi.nlm.nih.gov/pubmed/18358588 Phase-I Results Abstract
http://cordblood.net/cbrblog/haller-abstract.pdf Phase-I Results Whole Paper
http://clinicaltrials.gov/ct2/show/NCT00305344 Phase-I US Clinical Trial Record
The Phase-II Trial
It involves 15 patients (10 get treatment, 5 are the control group), and is scheduled to start March 2009 and finish collecting data by March 2012.
More details are described here:
http://clinicaltrials.gov/ct2/show/NCT00873925 Phase-II US Clinical Trial Record
My thoughts on this line of research are here; these are all personal opinions:
First, I think it is pretty limited in direct application, since it requires banked cord cells and is a honeymoon treatment. But I'm always hopeful that they might learn something that could be applied more broadly.
Second, I'm very interested in how long the effect lasts. Is it permanent, or does it go away over time?
Third, I think their "phase-II" experiment is tiny. Only 15 patients makes it smaller than some phase-I experiments that I've followed, and that's not a good sign.
Forth, this research "feels" to me like basic research where they're trying to better understand how adult stem cells and T-regulator cells might help type-1 diabetics, by experimenting on people. Rather than research on a short, straight line path to a cure.
Thanks to Ellen over at www.childrenwithdiabetes.com for pointing the phase-II trial out to me.
Joshua Levy
So the basic status is that Haller has completed a phase-I trial, and gotten good results, and has started a phase-II trial.
The Phase-I Trial
It is supposed to involve 23 patients and run from April 2005 to July 2010, however the data I've seen covered 8 patients and was published in June 2007, so it is an interim result.
That said, the results were good: a few months after the transfusion, the treated kids had an average A1C 1 point lower than untreated (7 compared to 8), they used about 2/3 as much insulin per kg of body weight as the untreated patients, and they generated more C-peptide in response to food (meaning they generated more of their own insulin).
For the phase-I trial:
http://cordblood.cryosite.com/UserFiles/File/Cord%20Blood%20and%20Diabetes.pdf Nice summary
http://www.ncbi.nlm.nih.gov/pubmed/18358588 Phase-I Results Abstract
http://cordblood.net/cbrblog/haller-abstract.pdf Phase-I Results Whole Paper
http://clinicaltrials.gov/ct2/show/NCT00305344 Phase-I US Clinical Trial Record
The Phase-II Trial
It involves 15 patients (10 get treatment, 5 are the control group), and is scheduled to start March 2009 and finish collecting data by March 2012.
More details are described here:
http://clinicaltrials.gov/ct2/show/NCT00873925 Phase-II US Clinical Trial Record
My thoughts on this line of research are here; these are all personal opinions:
First, I think it is pretty limited in direct application, since it requires banked cord cells and is a honeymoon treatment. But I'm always hopeful that they might learn something that could be applied more broadly.
Second, I'm very interested in how long the effect lasts. Is it permanent, or does it go away over time?
Third, I think their "phase-II" experiment is tiny. Only 15 patients makes it smaller than some phase-I experiments that I've followed, and that's not a good sign.
Forth, this research "feels" to me like basic research where they're trying to better understand how adult stem cells and T-regulator cells might help type-1 diabetics, by experimenting on people. Rather than research on a short, straight line path to a cure.
Thanks to Ellen over at www.childrenwithdiabetes.com for pointing the phase-II trial out to me.
Joshua Levy
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