Dr. Gitelman at UCSF has started a Phase-II human trial aimed at using ATG to cure (or lessen) type-1 diabetes. The goal of this study is to preserve remaining beta cells for people within 100 days from diagnosis. This study started in August 2007, and is expected to run until June 2011. So far it has enrolled 11 out of an expected 66 patients. It's a four day treatment (in hospital), and 12 follow up visits over a 2 year period. They are recruiting at a total of 9 sites (growing to 13), which are listed in the clinical trial page linked below.
Here is a quick summary of how they hope ATG (Thymoglobulin) will work:
Type 1 diabetes is caused by destruction of insulin-producing beta cells by T cells, part of the immune system. Thymoglobulin is a mixture of different antibodies that target T cells. This mixture includes the anti-CD3 antibody (and anti-CD3 treatments are in Phase-III trials already, having completed successful Phase-I and II trials). The researchers hope that this multi-faceted approach will be even more successful and have a longer lasting effect than with anti-CD3 alone, and may treat diabetes by several mechanisms. First, it lowers the number of T cells, so there are fewer to attack the beta cells. It also seems to alter the T cells remaining behind, rendering them less likely to be destructive. Following this depletion, the T cells that grow back in the following weeks may be reset and have a healthier balance (meaning that a special type of T cells, called regulatory T cells, will help keep the destructive T cells in check).
Using ATG to cure type-1 diabetes is an idea that flows from two sources. The first source is a line of clinical trials aimed directly at curing type-1 with ATG. Eisenbarth's work of long ago, a Phase-I trial done in Europe, etc. But it also has another source, which is Burt's Brazilian research as described below.
Discussion: How to Follow Up Burt?
One of the questions that I'm occasionally asked is this: when will there be a follow up to Burt's Brazilian research? When will there be a Burt, phase-II? This is a natural question, because Burt has -- by far -- the best results of any one. Many patients on that trial went years without using external insulin. No other study comes close. So an obvious question is: how do you move forward with that research.
Burt's research is the opposite of most. Most researchers use the smallest possible doses during phase-I. Phase-I is targeted at safety, so they use small doses to assure safety even at the expense of effectiveness. So for most studies, for phase-II studies, they move forward by raising the dose to try to make a safe treatment a more effective one. But Burt's research is the opposite. The effectiveness is the strongest yet, but there are real questions about safety. So you would NOT follow it up by raising the doses!
One way to follow up Burt's relative success, is by turning down the dose. Trade off a little effectiveness for added safety. Oversimplified a little: Burt's research involves using three drugs (ATG, GCSF, and cyclophosphamide), and reinjecting the patient's own precursor bone marrow cells (previously removed). Dosing with just ATG can be viewed as a "kinder, gentler" Burt. Especially since the cyclophosphamide is the most risky drug of the bunch. (I'll be posting on two GCSF clinical trials in the coming weeks.)
Since I'm a software engineer, I'll use a software analogy: Burt is doing a "hard reboot", Gitelman is trying for a "soft reboot".
Notes
One of the complexities of following the research, is that ATG is referred to by many different names by different groups. For example: Thymoglobulin, rATG, hATG, ATGAM, antithymocyte globulin, etc.
The cells that Burt is removing and then reinjecting are sometimes called "precursor bone marrow cells" and other times "adult stem cells".
The lead investigator for this clinical trial is Dr. Gitelman at UCSF. For those of you at Bearskin Meadows: yes, this is the same "Dr. Steve" who is often up there. I'm indebted to Dr. Gitelman for his insights into Burt's research and how it relates to other research, including his own. All mistakes, opinions, and oversimplifications are my own.
Patient oriented information on this trial:
http://www.type1diabetestrial.org
Previous Blog postings on this
http://cureresearch4type1diabetes.blogspot.com/search/label/ATG (blog on ATG)
http://cureresearch4type1diabetes.blogspot.com/search/label/Burt (blog on Burt)
http://cureresearch4type1diabetes.blogspot.com/search/label/Gitelman (blog on Gitelman)
Web pages (but these need updating):
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#ThymoglobulinalsoknownasATGbyGitelman (Gitelman)
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#ATGandothersbyBurtatUniversityofSaoPaulo (Burt)
Clinical Trial records for this study:
http://www.clinicaltrials.gov/ct2/show/NCT00515099 (Phase-II ATG)
http://www.clinicaltrials.gov/ct2/show/NCT00190502 (Phase-I ATG)
http://www.clinicaltrials.gov/ct/show/NCT00315133 (Burt)
Joshua Levy
Saturday, August 29, 2009
Sunday, August 23, 2009
Update on Pescovitz's Rituximab Phase-II trial
Pescovitz (and team from TrialNet) have finished a phase-II human trial of Rituximab, and the results have been accepted for publication at a big-name scientific journal. Unfortunately, that journal has embargoed the result data until publication, so I don't actually know the details of how well it worked. The good news, is that the study's authors did an oral presentation at ADA 2009, and (I'm told) that the results were good, but not as good as with the anti-CD3 monoclonal antibody drugs from Macrogenics or ToleRx. Those drugs preserved beta cell functionality for at least a year after treatment. Basically, untreated people lost half their ability to produce insulin in the year after onset of type-1 diabetes, but treated people retained about 95% of their ability. Rituximab was not as successful as that, but did preserve some insulin production.
Rituximab is a monoclonal antibody, a product of Genetech (now a division of Roche), and already approved by the US FDA for rheumatoid arthritis and several cancers. You can read more about it here:
http://en.wikipedia.org/wiki/Rituximab
It works by attacking B cells that have the CD20 marker. These B cells are part of the immune system and completely different that the beta cells (sometimes called B cells) in the pancreas. The immune system has many different types of both B cells and T cells. Most drugs currently being tested to cure type-1 diabetes target T cells. (For example: MacroGenics, ToleRx, Diamyd, Faustman, ATG, Abatacept, etc.) Rituximab is targeting a completely different type of cell (B rather than T). It is thought to work because B cells may interact with T cells influencing their targeting to attack beta cells. So this study is interesting, both because the results are good, but also because it potentially opens up a whole new area to understand as part of the cause of type-1 diabetes, and that means a whole new area where a cure or treatment might be found.
A follow on trial of Rituximab is currently being designed. It will probably involve repeated dosing of the drug. Obviously, I'll post when that clinical trial starts.
Discussion (Why many different treatments might be more effective.)
Right now, we have at least 5 drugs in phase-II or III human trials that, when given during the honeymoon phase, result in the patient loosing only half as much insulin production capacity, as if they were not given the drug. These include Rituximab, Diamyd's GAD65, several different anti-CD3s, and (maybe) Alpha Interferon. There are three ways of looking at these results:
The pessimist: "I don't want five half-way cures. I want one actual cure. Come back when you have something that works."
The engineer: "If it works half way now, then maybe we can improve it a little so it is three quarters working in a year or two, and 90% working a year or two after that and...."
The optimist: "Maybe we don't need a single cure. Maybe the proper combination of the many half cures we have will work right now, or will work for some people."
So if you're an optimist, then having several different treatments for type-1 diabetes which each target a different part of the autoimmune attack, is a good thing. We're used to thinking of a cure as being one pill or one operation or one something. In fact, for many of the more complex diseases (such as cancers, etc.), it is a cocktail of drugs which work together to have the best effect. And type-1 diabetes is surely a complex disease!
Of course "drug cocktails" are harder to test and harder to get approval for, and generally slower to market. In the past there has been discussion of pairing something that stops the autoimmune attack with something that regrows beta cells. That is one type of "drug cocktail", but it also may be that the thing that stops the autoimmune attack with the fewest side effects is itself a mixture of several drugs which target different parts of the autoimmune response.
Thanks to Dr. Gitelman for insightful discussions of this research. All mistakes here are my own.
Clinical Trial Record for the Rituximab trial is here:
http://www.clinicaltrials.gov/ct2/show/NCT00279305
Joshua Levy
Rituximab is a monoclonal antibody, a product of Genetech (now a division of Roche), and already approved by the US FDA for rheumatoid arthritis and several cancers. You can read more about it here:
http://en.wikipedia.org/wiki/Rituximab
It works by attacking B cells that have the CD20 marker. These B cells are part of the immune system and completely different that the beta cells (sometimes called B cells) in the pancreas. The immune system has many different types of both B cells and T cells. Most drugs currently being tested to cure type-1 diabetes target T cells. (For example: MacroGenics, ToleRx, Diamyd, Faustman, ATG, Abatacept, etc.) Rituximab is targeting a completely different type of cell (B rather than T). It is thought to work because B cells may interact with T cells influencing their targeting to attack beta cells. So this study is interesting, both because the results are good, but also because it potentially opens up a whole new area to understand as part of the cause of type-1 diabetes, and that means a whole new area where a cure or treatment might be found.
A follow on trial of Rituximab is currently being designed. It will probably involve repeated dosing of the drug. Obviously, I'll post when that clinical trial starts.
Discussion (Why many different treatments might be more effective.)
Right now, we have at least 5 drugs in phase-II or III human trials that, when given during the honeymoon phase, result in the patient loosing only half as much insulin production capacity, as if they were not given the drug. These include Rituximab, Diamyd's GAD65, several different anti-CD3s, and (maybe) Alpha Interferon. There are three ways of looking at these results:
The pessimist: "I don't want five half-way cures. I want one actual cure. Come back when you have something that works."
The engineer: "If it works half way now, then maybe we can improve it a little so it is three quarters working in a year or two, and 90% working a year or two after that and...."
The optimist: "Maybe we don't need a single cure. Maybe the proper combination of the many half cures we have will work right now, or will work for some people."
So if you're an optimist, then having several different treatments for type-1 diabetes which each target a different part of the autoimmune attack, is a good thing. We're used to thinking of a cure as being one pill or one operation or one something. In fact, for many of the more complex diseases (such as cancers, etc.), it is a cocktail of drugs which work together to have the best effect. And type-1 diabetes is surely a complex disease!
Of course "drug cocktails" are harder to test and harder to get approval for, and generally slower to market. In the past there has been discussion of pairing something that stops the autoimmune attack with something that regrows beta cells. That is one type of "drug cocktail", but it also may be that the thing that stops the autoimmune attack with the fewest side effects is itself a mixture of several drugs which target different parts of the autoimmune response.
Thanks to Dr. Gitelman for insightful discussions of this research. All mistakes here are my own.
Clinical Trial Record for the Rituximab trial is here:
http://www.clinicaltrials.gov/ct2/show/NCT00279305
Joshua Levy
Sunday, August 16, 2009
Brod Completes Phase-II trial of Alpha Interferon
Brod has finished a Phase-II clinical trial of oral interferon alpha, as a possible honeymoon cure of type-1 diabetes, and has published the results. The study involved 128 people, some of whom got 5k units of interferon, others got 30k, and others got none at all; daily doses for one year. After a year, natural insulin production in response to a meal was measured. The experiment was random assignment and double blind.
The results were this: The untreated group lost 56% of their insulin production one year after diagnosis. The group treated with 30k lost 46% but the group treated with 5k lost only 29%. So the best-to-worst summary is that the treated group lost about half as much insulin production as the untreated group. This result is very similar to Diamyd's and ToleRx's Phase-II results.
The press release describes Brod's theory this way:
This clinical trial was funded by Diabetes Action Research and Education Foundation, the US Gov and the Children's Hospital of Minnesota Foundation.
Press release is here:
http://www.sciencedaily.com/releases/2009/07/090701083049.htm
Abstract of the results is here:
http://www.ncbi.nlm.nih.gov/pubmed/19564474?dopt=Abstract
Clinical Trial Record is here:
http://www.clinicaltrials.gov/ct2/show/NCT00024518
(By the way: this is one of the worst clinical trial records I've seen. Especially since the US Gov is a major contributor to this work. There is no end date, Brod is not listed as primary investigator, no description of how many patients got which treatment, etc.)
There is also another clinical trial record here, but I'm not sure if this is the same clinical trial, a related one, or a totally different one:
http://www.clinicaltrials.gov/ct2/show/NCT00005665
Joshua Levy
The results were this: The untreated group lost 56% of their insulin production one year after diagnosis. The group treated with 30k lost 46% but the group treated with 5k lost only 29%. So the best-to-worst summary is that the treated group lost about half as much insulin production as the untreated group. This result is very similar to Diamyd's and ToleRx's Phase-II results.
The press release describes Brod's theory this way:
Brod's theory is that autoimmune diseases, which occur when the body is attacked by its own immune system, are actually an alpha interferon immunodeficiency syndrome. Interferons are a group of proteins produced by cells in response to an attack by a virus.My translation of this, is that he thinks that type-1 (and other autoimmune diseases) are caused by a lack of alpha interferon. Therefore, dosing with alpha interferon is an obvious path to a cure.
This clinical trial was funded by Diabetes Action Research and Education Foundation, the US Gov and the Children's Hospital of Minnesota Foundation.
Press release is here:
http://www.sciencedaily.com/releases/2009/07/090701083049.htm
Abstract of the results is here:
http://www.ncbi.nlm.nih.gov/pubmed/19564474?dopt=Abstract
Clinical Trial Record is here:
http://www.clinicaltrials.gov/ct2/show/NCT00024518
(By the way: this is one of the worst clinical trial records I've seen. Especially since the US Gov is a major contributor to this work. There is no end date, Brod is not listed as primary investigator, no description of how many patients got which treatment, etc.)
There is also another clinical trial record here, but I'm not sure if this is the same clinical trial, a related one, or a totally different one:
http://www.clinicaltrials.gov/ct2/show/NCT00005665
Joshua Levy
Wednesday, July 15, 2009
News from Bayhill on their BHT-3021 Treatment
Bayhill is in the middle of a phase-I clinical trial of BHT-3021 which is designed to train the body's immune system not to attack itself. Recently they announced both scientific results, and a huge corporate deal.
First the science: the phase-I study is still ongoing, but based on 12 months of data for one dose level, and 6 months for other dose levels, BHT-3021 appears to preserve beta cell function in type-1 diabetics (as measured by C-peptide production and A1C levels, for example). The differences were small. For example the patients who got the highest level of drug reported on had A1C levels about .44 lower than those who were not treated. This study was open to anyone who had type-1 for less than 5 years, so not just "honeymooners only".
You can see the abstract here:
http://ww2.aievolution.com/ada0901/index.cfm?do=abs.viewAbs&abs=5458
Second, the corporate deal. Basically, Genetech (now owned by Roche) is going to buy BHT-3021. Genetech will pay Bayhill for this drug, they will reimburse Bayhill for the ongoing costs of the phase-I trial, and Genetech will run future phase-II and III trials. Genetech will market any resulting drug, and Bayhill will get royalties.
For a small company, like Bayhill, this is really the pot of gold at the end of the rainbow. Their lead product candidate is being bought by a major player based on it's success to date. From a money point of view, for a treatment still in the middle of phase-I trials, this is about as good as you can do.
More details are in the press release here:
http://www.bayhilltherapeutics.com/art/BHT_GNE_PartnershipReleaseFNL6-9-09.pdf
Joshua Levy
Thursday, June 25, 2009
LCT To Start Phase-I Human Trial in New Zealand
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
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
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
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