Otelixizumab (Tolerx / GlaxoSmithKline) Fails Phase-III Trial
The official quote is "did not meet the primary efficacy endpoint". Basically, the the people who got the drug did not do better than those who did not, in the the most important measurement of success. The primary endpoint for this experiment was C-peptide generation, which is a marker for natural insulin production. Basically, they were hoping that giving this drug would help honeymoon type-1 diabetics generate more of their own insulin, but it did not.
In terms of actions: they have stopped enrollment in their second phase-III trial (DEFEND-2), which shows that they think that there is little to no hope of moving forward with this drug at this time.
So that is about as dead as a phase-III trial can get.
Press release: http://classic.cnbc.com/id/42028160
Tolerx blog: http://tolerx.com/index.php?page=greenchair&entry=committed-to-the-promise-of-our-normalization-immunotherapy-platform
DEFEND-1: http://www.clinicaltrials.gov/ct2/show/NCT00678886
DEFEND-2: http://www.clinicaltrials.gov/ct2/show/NCT01123083
A Little Discussion
This is not completely unexpected, because there was another similar drug (Teplizumab), which was also an anti-CD3 monoclonal antibody which was also in phase-III clinical trials and just a few months ago, it failed as well. And for the same reason: did not cure/improve people. Neither trial had any safety problems.
There is still one anti-CD3 monoclonal antibody out there. It is NI-0401 by NovImmune, and is in phase-II clinical trials. Unfortunately, I've never been able to find results for their phase-I study, so I don't hold out much hope. If you know anything about NovImmune's NI-0401 results, or where they were published, then please tell me.
Previous blogging on Teplizumab:
http://cureresearch4type1diabetes.blogspot.com/search/label/Teplizumab
Previous blogging on NI-0401:
http://cureresearch4type1diabetes.blogspot.com/search/label/NI-0401
So where are we now?
Years ago, there was only one treatment in phase-III trials: DiaPep277. Last year, there were four. Since then, two have failed and none have entered, so we are down to two: GAD65 and DiaPep277. GAD65 is expected to announce their first phase-III results in the next 3 months, but DiaPep277 results are much farther away.
The official musical accompaniment for this blog entry is "River of No Return" from The Jeff Healey Band's album "See the Light".
It's a cold hard lesson, that you're gonna learn, on the river of no return....
Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.
Blog: http://cureresearch4type1diabetes.blogspot.com To Get as Email Join here: http://groups.google.com/group/type-1-diabetes-clinical-trials-news
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials
Showing posts with label Otelixizumab. Show all posts
Showing posts with label Otelixizumab. Show all posts
Monday, March 14, 2011
Tuesday, September 28, 2010
Possible Cures for Type-1 in the News (Sept)
An Encapsulated Human Islet Transplant Cure in Phase-I
For the last many years, I have thought that LCT was the only company actively doing clinical trials on an encapsulated islet cell cure for type-1 diabetes. However, I recently found this clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT00790257
These guys are testing human encapsulated islet cells (so not pig cells, as LCT is using). They started in November 2008 and ending in December 2013, and includes 15 people. They're doing this one trial in two phases, the first phase is only open to people who have already had an organ transplant (which I'm sure is delaying the study, since it takes a long time to recruit people like that). They call their device a "Monolayer Cellular Device", and the work is being done in Belgium
The other piece of news is a little more technical. Here is the key quote:
What this means is that they believe that their experiments show that Otelixizumab works in two different ways. First, it blocks the bad killer T-cells. The cells that are directly attacking the pancreas. Second it increases the actions of the regulatory T-cells, which are cells designed to control killer T-cells. That is potentially a powerful combination (although it will be interesting to see how long it lasts). Another interesting piece of data is how selective is it? Attacking the bad killer T cells is one thing, but it would be even better to NOT attack the good killer T cells. The press release implies that it is selective, (which would be great) but this is a case where we need to see the numbers, to see exactly how selective it is.
Both Tolerx (Otelixizumab) and MacroGenics (Teplizumab) Start Separate Subcutaneous Trials
Both Tolerx and MacroGenics are starting clinical trials designed to test their respective drugs when given subcutaniously. The current clinical trials for both drugs require an IV (drip into a blood vein). Those can not be done at home. However, these studies are checking to see if the respective drugs can be injected just under the skin (called Subcutaneously, or SubQ). That is how insulin is injected. So if these clinical trials are successful, that means people would be able to inject themselves at home, rather than go to a clinic and have a nurse do it.
These are both phase-I studies and both are still recruiting new patients.
The Teplizumab study has 71 people, and should complete in July 2012, and is honeymoon only. You must be within 1 year of diagnosis.
The Otelixizumab study has 28 people, and should complete was supposed to finish in July 2010. This study is not limited to honeymoon diabetics, but you must have A1C numbers above 9%, you must generate a little C-peptide. If the study shows that the drug has the same (or similar) effect when injected like just under the skin as they see with IV drips, then I would love to see how it effects long established diabetics.
Clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT01189422 Teplizumab
Clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT00946257 Otelixizumab
Testing C-Peptides: Fasting as good as Stimulated?
A little background: When your body makes insulin, it also makes a small molecule called C-Peptide. This is very important to diabetes research, because if a researcher sees insulin in a person's blood, there is no way to know if that insulin came from an injection or from internal production. However, C-peptide only comes from internal insulin production. So when someone measures if a drug helps insulin production, what they really do is measure C-peptide. Years ago the US FDA adopted this standard, so that in order to get a new drug approved to help a diabetic produce more insulin, the drug company must show evidence that the new drug increases C-peptide levels. (Paradoxically, measuring insulin is considered a second rate way to testing insulin production, because the type-1 diabetic might have injected more insulin for any number of reasons.) C-peptide is the gold standard of measuring insulin production.
But there are two ways to measure C-peptide: fasting and after a meal (which is sometimes called a "challenge" or "stimulated"). The fasting one is quicker and easier to do (at least for the researchers, the patient may prefer a meal :-) ) But the meal one is considered a better measure of effectiveness. Basically, a fasting C-peptide measure tells you how well your body creates "basil" (ie. no food) insulin. While the meal test tells you how well your body creates "bolus" insulin (in response to food). The meal one is considered better, but the fasting one is easier.
The summary of this poster session is that the results of the two different tests are linked. So that doing a fasting test predicts what will happen for a meal test, and doing a meal test predicts what will happen for a fasting test. If confirmed by other trials, this will make it cheaper and easier to do clinical trials in the future (especially for large numbers of people) since you will only need to do a fasting test.
Press release: http://www.sys-con.com/node/1544442
Novocell Terminates Encapsulated Islet Transplant Clinical Trial
Years ago, Novocell was developing an encapsulated islet cell transplant cure, similar to LCT, although my memory was that they were using human islet cells, not pig cells. In any case, the research did not move forward. They started a phase-I clinical trial in 2005, but in 2006 they stopped recruiting for it. I think that it has been moribund ever since, but they just (April 2010) officially terminated it.
The company recently changed it's name to ViaCyte, and is working on an encapsulated islet cure called "Pro-Islet". They are doing animal ("pre-clinical") studies, so I'm not following it as yet.
http://www.clinicaltrials.gov/ct2/show/NCT00260234
Final End of TT-223
A few days ago, Transition Therapeutics announced the end of clinical research for TT-223:
My translation: Even when we mixed it with another drug, it still did not work well enough to move forward.
So that's about as dead as you can get. (Although INGAP went through this same process and was later "reborn" by the original developers who thought it had a future even though their big pharma backers did not. Those guys are still doing clinical trials of INGAP (renamed Exsulin) and who knows what will happen?)
A little history:
TT-223 was one of the possible cures in existence when I started tracking them on my original web status page. They were initially funded by JDRF, but then Eli Lily took over development from Transition Therapeutics, the small company that JDRF had funded. JDRF got it's money back at this point because their funding was no longer needed, and they then reinvested it in something else. But Eli only continued the type-2 testing, not the type-1 testing. So almost exactly a year ago I blogged about this, and said that TT-223 was dead as far as a cure for type-1 (at least until someone started testing it again in type-1 diabetics). You can read that post here:
http://cureresearch4type1diabetes.blogspot.com/2009/09/two-possible-cures-go-to-boneyard.html
At that point I stopped following TT-223. However, an alert reader continued to follow them, and so when they issued the press release above, that reader forwarded it to me. Thanks! You know who you are.
Rituximab in the Real World
I have previously blogged on Rituximab (sold as Rituxan):
http://cureresearch4type1diabetes.blogspot.com/search/label/Rituximab
This drug is already approved for use in the US for certain diseases, and there was a recently published article on it's safety as applied to rheumatoid arthritis, which is an autoimmune disease of the same general family as type-1 diabetes. You can read that here:
News coverage: http://www.medpagetoday.com/Rheumatology/Arthritis/22038
Abstract: http://onlinelibrary.wiley.com/doi/10.1002/art.27555/abstract
This study was based on a registry of over a thousand French citizens who were treated with Rituximab and who were followed up for at least a year. So this is a much bigger study than the Phase-I study for type-1 diabetics, which was less than 90 people for 1 year.
There were two interesting results, from my point of view:
First, the overall rate of serious infection was about the same in this trial as it had been in the trials that were used to get approval for the drug in the first place. That's good news, because those approval trials generally exclude patients who have "co-morbidities" (that is: something else wrong with them). On the other hand, real world use include patients who have several different diseases. (Especially rheumatoid arthritis.) And having more than one disease raises the chance of serious infection, and that is exactly what this study was looking at. So it is good news that the side effects were no worse for real world use as for experimental use.
Second, the serious infection rate was much higher (about 5 times as high) for people who had "low IgG levels". So the authors of the study suggest that people getting Rituximab get tested for that before each dosing. Other co-morbidities that were associated with a higher chance of serious infection included chronic lung disease and/or cardiac insufficiency and extraarticular involvement. (Which are not common in type-1 diabetics, and especially not young ones.)
I think this is good safety news for this drug. Both because it shows it is safe when used "as-is", but also because it provides a clear path to even higher levels of safety via a simple screening process.
Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials
For the last many years, I have thought that LCT was the only company actively doing clinical trials on an encapsulated islet cell cure for type-1 diabetes. However, I recently found this clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT00790257
These guys are testing human encapsulated islet cells (so not pig cells, as LCT is using). They started in November 2008 and ending in December 2013, and includes 15 people. They're doing this one trial in two phases, the first phase is only open to people who have already had an organ transplant (which I'm sure is delaying the study, since it takes a long time to recruit people like that). They call their device a "Monolayer Cellular Device", and the work is being done in Belgium
News on Otelixizumab by Tolerx
I have two tidbits on Tolerx's Otelixizumab. The first is from news article which was discussing the start of their DEFEND-2 clinical trial, which is a confirmatory phase-III trial. So that is the last stage before FDA approval. So, as the quote shows below, Tolerx is starting to look to eventual approval:If the trial [DEFEND-2] is successful, the company plans to send the drug candidate to the U.S. Food and Drug Administration in 2012.Obviously that is good news. For comparison, Diamyd was talking about starting the approval process in 2011, and LCT at one time was 2011, but more recently was 2013. To the best of my knowledge we have never started the marketing approval process for a non-insulin drug to target type-1 diabetes. So having three possible starts in the next 3 years is great. Although that is tempered by the fact that only one of these treatments has been tested on established diabetics, and none of them represents a cure so far.
The other piece of news is a little more technical. Here is the key quote:
The new research findings support existing data suggesting that otelixizumab may work in patients with new-onset type 1 diabetes by blocking the function of T killer/effector cells that mistakenly attack and destroy insulin-producing beta cells, while simultaneously stimulating T regulatory cells that are thought to protect against future T killer/effector destruction. Clinical data from the recently completed DEFEND-1 Phase 3 study and the ongoing DEFEND-2 confirmatory Phase 3 study will be evaluated in light of these new findings to determine whether this dual effect of otelixizumab is consistent with results from patients who have received otelixizumab.Press release: http://www.prnewswire.com/news-releases/tolerx-presents-research-at-european-diabetes-meeting-and-enrolls-first-patient-in-europe-in-the-defend-2-phase-3-clinical-study-in-type-1-diabetes-103610664.html
What this means is that they believe that their experiments show that Otelixizumab works in two different ways. First, it blocks the bad killer T-cells. The cells that are directly attacking the pancreas. Second it increases the actions of the regulatory T-cells, which are cells designed to control killer T-cells. That is potentially a powerful combination (although it will be interesting to see how long it lasts). Another interesting piece of data is how selective is it? Attacking the bad killer T cells is one thing, but it would be even better to NOT attack the good killer T cells. The press release implies that it is selective, (which would be great) but this is a case where we need to see the numbers, to see exactly how selective it is.
Both Tolerx (Otelixizumab) and MacroGenics (Teplizumab) Start Separate Subcutaneous Trials
Both Tolerx and MacroGenics are starting clinical trials designed to test their respective drugs when given subcutaniously. The current clinical trials for both drugs require an IV (drip into a blood vein). Those can not be done at home. However, these studies are checking to see if the respective drugs can be injected just under the skin (called Subcutaneously, or SubQ). That is how insulin is injected. So if these clinical trials are successful, that means people would be able to inject themselves at home, rather than go to a clinic and have a nurse do it.
These are both phase-I studies and both are still recruiting new patients.
The Teplizumab study has 71 people, and should complete in July 2012, and is honeymoon only. You must be within 1 year of diagnosis.
The Otelixizumab study has 28 people, and should complete was supposed to finish in July 2010. This study is not limited to honeymoon diabetics, but you must have A1C numbers above 9%, you must generate a little C-peptide. If the study shows that the drug has the same (or similar) effect when injected like just under the skin as they see with IV drips, then I would love to see how it effects long established diabetics.
Clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT01189422 Teplizumab
Clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT00946257 Otelixizumab
Testing C-Peptides: Fasting as good as Stimulated?
A little background: When your body makes insulin, it also makes a small molecule called C-Peptide. This is very important to diabetes research, because if a researcher sees insulin in a person's blood, there is no way to know if that insulin came from an injection or from internal production. However, C-peptide only comes from internal insulin production. So when someone measures if a drug helps insulin production, what they really do is measure C-peptide. Years ago the US FDA adopted this standard, so that in order to get a new drug approved to help a diabetic produce more insulin, the drug company must show evidence that the new drug increases C-peptide levels. (Paradoxically, measuring insulin is considered a second rate way to testing insulin production, because the type-1 diabetic might have injected more insulin for any number of reasons.) C-peptide is the gold standard of measuring insulin production.
But there are two ways to measure C-peptide: fasting and after a meal (which is sometimes called a "challenge" or "stimulated"). The fasting one is quicker and easier to do (at least for the researchers, the patient may prefer a meal :-) ) But the meal one is considered a better measure of effectiveness. Basically, a fasting C-peptide measure tells you how well your body creates "basil" (ie. no food) insulin. While the meal test tells you how well your body creates "bolus" insulin (in response to food). The meal one is considered better, but the fasting one is easier.
The summary of this poster session is that the results of the two different tests are linked. So that doing a fasting test predicts what will happen for a meal test, and doing a meal test predicts what will happen for a fasting test. If confirmed by other trials, this will make it cheaper and easier to do clinical trials in the future (especially for large numbers of people) since you will only need to do a fasting test.
Press release: http://www.sys-con.com/node/1544442
Novocell Terminates Encapsulated Islet Transplant Clinical Trial
Years ago, Novocell was developing an encapsulated islet cell transplant cure, similar to LCT, although my memory was that they were using human islet cells, not pig cells. In any case, the research did not move forward. They started a phase-I clinical trial in 2005, but in 2006 they stopped recruiting for it. I think that it has been moribund ever since, but they just (April 2010) officially terminated it.
The company recently changed it's name to ViaCyte, and is working on an encapsulated islet cure called "Pro-Islet". They are doing animal ("pre-clinical") studies, so I'm not following it as yet.
http://www.clinicaltrials.gov/ct2/show/NCT00260234
Final End of TT-223
A few days ago, Transition Therapeutics announced the end of clinical research for TT-223:
Transition Therapeutics announced today [17 Sept 2010] that a clinical study of gastrin analogue TT-223 in combination with a Lilly proprietary GLP-1 analogue in patients with type 2 diabetes did not meet its efficacy endpoints. Given these findings, there will be no further development of TT-223.Press release: http://www.transitiontherapeutics.com/media/news.php
My translation: Even when we mixed it with another drug, it still did not work well enough to move forward.
So that's about as dead as you can get. (Although INGAP went through this same process and was later "reborn" by the original developers who thought it had a future even though their big pharma backers did not. Those guys are still doing clinical trials of INGAP (renamed Exsulin) and who knows what will happen?)
A little history:
TT-223 was one of the possible cures in existence when I started tracking them on my original web status page. They were initially funded by JDRF, but then Eli Lily took over development from Transition Therapeutics, the small company that JDRF had funded. JDRF got it's money back at this point because their funding was no longer needed, and they then reinvested it in something else. But Eli only continued the type-2 testing, not the type-1 testing. So almost exactly a year ago I blogged about this, and said that TT-223 was dead as far as a cure for type-1 (at least until someone started testing it again in type-1 diabetics). You can read that post here:
http://cureresearch4type1diabetes.blogspot.com/2009/09/two-possible-cures-go-to-boneyard.html
At that point I stopped following TT-223. However, an alert reader continued to follow them, and so when they issued the press release above, that reader forwarded it to me. Thanks! You know who you are.
Rituximab in the Real World
I have previously blogged on Rituximab (sold as Rituxan):
http://cureresearch4type1diabetes.blogspot.com/search/label/Rituximab
This drug is already approved for use in the US for certain diseases, and there was a recently published article on it's safety as applied to rheumatoid arthritis, which is an autoimmune disease of the same general family as type-1 diabetes. You can read that here:
News coverage: http://www.medpagetoday.com/Rheumatology/Arthritis/22038
Abstract: http://onlinelibrary.wiley.com/doi/10.1002/art.27555/abstract
This study was based on a registry of over a thousand French citizens who were treated with Rituximab and who were followed up for at least a year. So this is a much bigger study than the Phase-I study for type-1 diabetics, which was less than 90 people for 1 year.
There were two interesting results, from my point of view:
First, the overall rate of serious infection was about the same in this trial as it had been in the trials that were used to get approval for the drug in the first place. That's good news, because those approval trials generally exclude patients who have "co-morbidities" (that is: something else wrong with them). On the other hand, real world use include patients who have several different diseases. (Especially rheumatoid arthritis.) And having more than one disease raises the chance of serious infection, and that is exactly what this study was looking at. So it is good news that the side effects were no worse for real world use as for experimental use.
Second, the serious infection rate was much higher (about 5 times as high) for people who had "low IgG levels". So the authors of the study suggest that people getting Rituximab get tested for that before each dosing. Other co-morbidities that were associated with a higher chance of serious infection included chronic lung disease and/or cardiac insufficiency and extraarticular involvement. (Which are not common in type-1 diabetics, and especially not young ones.)
I think this is good safety news for this drug. Both because it shows it is safe when used "as-is", but also because it provides a clear path to even higher levels of safety via a simple screening process.
Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials
Tuesday, June 1, 2010
Possible Cures for Type-1 in the News (May)
I didn't quite get this out by the end of May, but it is the May update.....
Andromedia Starts DIA-AID2: Second phase-III Trial of DiaPep 277
Andromedia just (in April 2010) started their second phase-III trial, which will enroll 450 people and is planned to last until March 2014. Both the EU and the US require two large scale trials for approval of new drugs, so if this study and their earlier DIA-AID trial both work well, then the approval process can start mid-2014. It usually takes a year or two for marketing approval, so 2015 or 2016. This treatment has only been tested on honeymoon diabetics.
Neither this treatment nor ToleRx's (described below) will cure people by themselves. They are both attempts to preserve some beta cells and so either extend the honeymoon or make the continuing diabetes "less brittle" in terms of fewer quick BG drops. In both cases, I need to put together a blog posting on exactly how effective they were in their phase-II and early phase-III results.
Andromedia's DIA-AID2 page: http://www.andromedabio.com/clinical_trials.php
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01103284
ToleRx Starts DEFEND-2: Second phase-III trial of Otelixizumab
This must be the month for starting second (sometimes called "confirmatory") phase-III trials, since ToleRx is also starting one of these. The news is just as good as Andromedia. Actually better, since ToleRx hopes to finish their second phase-III by May 2013. The study will have 396 people. The same market approval math works here, so 2014 or 2015, but only if they finish their second phase-III as expected, and with the results they expect. Both of their phase-III trials are limited to honeymooners only (so any approval would only be for newly diagnosed). Their phase-II clinical trial (called "TTEDD") did enroll non-honeymooners. However, it looks like good results were only seen for honeymooners (but I don't have the details handy). That would explain why their phase-III trials are all honeymooners only.
TolerRx's DEFEND-2 page: http://www.clinicaltrials.gov/ct2/show/NCT01123083
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01123083
Data from XOMA Phase-I on Behcet's Disease
Previous blogging on XOMA 052: http://cureresearch4type1diabetes.blogspot.com/search/label/Xoma
Current Status on XOMA 052: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#Xoma052byXoma
Behcet's Disease is an auto-inflammatory condition, which is rare in the US, but more common in Turkey. Since XOMA 052 is an anti inflammatory, it is a natural drug to test on the disease. It's of interest to people with type-1 diabetes because XOMA 052 is also being tested for both type-1 and type-2 diabetes (in separate phase-II trials). Link to why inflammation might be a cause of diabetes:
http://joshualevy.pbworks.com/ConceptsAndBackground#Inflammation
(but remember that this is a minority opinion).
So, with all that a background, their results are very good (but on a very small group of people). This trial only included 4 people. However each person involved showed real improvement to their Behect's symptoms.
My take on this research is as follows: It shows that XOMA 052 has a major impact on inflammation in a situation similar to (but not identical with) type-1 diabetes. So, if inflammation is a causative factor, or if reducing inflammation allows the pancreas to regrow, then XOMA 052 has a good chance of being successful.
Also, there is news about Xoma's phase-II trial in type-1 diabetics. They have changed it considerably from the last time I looked. It is a 24 person study, which started in Feb 2009 and is expected to finish in July 2011. Since it lasts a year, if they finish enrollment in July 2010, then they will be on track to finish the study a year later. This trial is open to non-honeymoon diabetics only, but there is only one site: Zurich, Switzerland.
So there are now at least two phase-II trials aimed a curing diabetes via anti-inflammatories, and they will both have results in 2011, so that might be a pivotal year for the whole idea of cures based on anti-inflammatories.
News: http://www.marketwatch.com/story/abstract-published-on-initial-results-from-xoma-052-clinical-trial-in-behcets-disease-2010-05-12?reflink=MW_news_stmp
Abstract: https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=19942&ItemsPerPage=20&AppliedFilter=[SubmitterFullName]%20Like%20%27Ahmet%20%%27&ShowOnlyInFinalAcceptance=true
Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.
Andromedia Starts DIA-AID2: Second phase-III Trial of DiaPep 277
Andromedia just (in April 2010) started their second phase-III trial, which will enroll 450 people and is planned to last until March 2014. Both the EU and the US require two large scale trials for approval of new drugs, so if this study and their earlier DIA-AID trial both work well, then the approval process can start mid-2014. It usually takes a year or two for marketing approval, so 2015 or 2016. This treatment has only been tested on honeymoon diabetics.
Neither this treatment nor ToleRx's (described below) will cure people by themselves. They are both attempts to preserve some beta cells and so either extend the honeymoon or make the continuing diabetes "less brittle" in terms of fewer quick BG drops. In both cases, I need to put together a blog posting on exactly how effective they were in their phase-II and early phase-III results.
Andromedia's DIA-AID2 page: http://www.andromedabio.com/clinical_trials.php
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01103284
ToleRx Starts DEFEND-2: Second phase-III trial of Otelixizumab
This must be the month for starting second (sometimes called "confirmatory") phase-III trials, since ToleRx is also starting one of these. The news is just as good as Andromedia. Actually better, since ToleRx hopes to finish their second phase-III by May 2013. The study will have 396 people. The same market approval math works here, so 2014 or 2015, but only if they finish their second phase-III as expected, and with the results they expect. Both of their phase-III trials are limited to honeymooners only (so any approval would only be for newly diagnosed). Their phase-II clinical trial (called "TTEDD") did enroll non-honeymooners. However, it looks like good results were only seen for honeymooners (but I don't have the details handy). That would explain why their phase-III trials are all honeymooners only.
TolerRx's DEFEND-2 page: http://www.clinicaltrials.gov/ct2/show/NCT01123083
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01123083
Data from XOMA Phase-I on Behcet's Disease
Previous blogging on XOMA 052: http://cureresearch4type1diabetes.blogspot.com/search/label/Xoma
Current Status on XOMA 052: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#Xoma052byXoma
Behcet's Disease is an auto-inflammatory condition, which is rare in the US, but more common in Turkey. Since XOMA 052 is an anti inflammatory, it is a natural drug to test on the disease. It's of interest to people with type-1 diabetes because XOMA 052 is also being tested for both type-1 and type-2 diabetes (in separate phase-II trials). Link to why inflammation might be a cause of diabetes:
http://joshualevy.pbworks.com/ConceptsAndBackground#Inflammation
(but remember that this is a minority opinion).
So, with all that a background, their results are very good (but on a very small group of people). This trial only included 4 people. However each person involved showed real improvement to their Behect's symptoms.
My take on this research is as follows: It shows that XOMA 052 has a major impact on inflammation in a situation similar to (but not identical with) type-1 diabetes. So, if inflammation is a causative factor, or if reducing inflammation allows the pancreas to regrow, then XOMA 052 has a good chance of being successful.
Also, there is news about Xoma's phase-II trial in type-1 diabetics. They have changed it considerably from the last time I looked. It is a 24 person study, which started in Feb 2009 and is expected to finish in July 2011. Since it lasts a year, if they finish enrollment in July 2010, then they will be on track to finish the study a year later. This trial is open to non-honeymoon diabetics only, but there is only one site: Zurich, Switzerland.
So there are now at least two phase-II trials aimed a curing diabetes via anti-inflammatories, and they will both have results in 2011, so that might be a pivotal year for the whole idea of cures based on anti-inflammatories.
News: http://www.marketwatch.com/story/abstract-published-on-initial-results-from-xoma-052-clinical-trial-in-behcets-disease-2010-05-12?reflink=MW_news_stmp
Abstract: https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=19942&ItemsPerPage=20&AppliedFilter=[SubmitterFullName]%20Like%20%27Ahmet%20%%27&ShowOnlyInFinalAcceptance=true
Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.
Wednesday, April 21, 2010
ToleRx Publishes Phase-II Data, 4 Year Follow Up
ToleRx In The News
Overview of what TolerRx is doing: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#OtelixizumabbyToleRx
Previous blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/ToleRx
In January, ToleRx announced that their phase-III clinical trial of Otelixizumab was completely enrolled (which I previously reported on). Now ToleRx has two more important pieces of information:
- They are going to start a second phase-III clinical trial, called DEFEND-2.
- Publishing 4 year follow up data on an earlier phase-II clinical trial (called TTEDD).
The second phase-III clinical trial is important because you need two successful trials for US FDA or EU EMEA approval. So the sooner they start that second trial the sooner they can get approved.
The 4 year follow up data is important, because it can tell us how well it works. Remember that the goal of TTEDD was to determine the best dosing system for the phase-III trials, so we should expect better results from the phase-III trials, and lower side effects, then reported on here:
For an example of what this means, if you assume a kid who weighs about 50kg, at the end of 4 years, they might have increased their insulin usage by about 16 units. However, those that received the treatment only increased their usage by about 5 units. Both went up, but the untreated patients went up a lot more.Treatment with ChAglyCD3 delayed the rise in insulin requirements of patients with recent-onset diabetes and reduced its amplitude over 48 months (+0.09 vs +0.32 U/ kg/ day in the placebo group). Using multivariate analysis this effect was correlated with higher baseline residual beta cell function and a younger age.
Another issue for new drugs is safety, and here the news is good:
In this reported study, otelixizumab administration was associated with transient symptoms during dosing including flu-like syndrome and transient perturbation of Epstein Barr Virus (EBV). During the 48 months of follow-up there were no EBV related symptoms, no higher incidence of infections, and no lymphoproliferative or other types of cancer observed. Following the 18 month efficacy results of the present study, Tolerx has optimized the otelixizumab dosing regimen to minimize adverse events, with encouraging data on clinical effect.Which I translate as: some people got flu like symptoms during treatment, but there were no long term side effects at all. Note that about 40 people were treated, and this was a 4 year follow up, so this will not close the book on safety issues, but it is clearly good news.
One interesting tid-bit is that the TTEDD study is not limited to honeymoon diabetics, although the follow on (DEFEND-1 and DEFEND-2) studies are. Because the earlier study is open to non-honeymooners, but the later studies are not, I think it is reasonable to assume that this treatment did not work well for non-honeymooners. However, it would interesting to see compare the TTEDD data for honeymooners vs. non-honeymooners. The TTEDD study is still recruiting new patients.
Abstract: http://www.springerlink.com/content/p3572576j25l2640/
Press Release: http://www.prnewswire.com/news-releases/single-short-course-of-tolerxs-otelixizumab-provides-prolonged-preservation-of-beta-cell-function-87773937.html
Company Blog: http://www.tolerx.com/index.php?page=greenchair
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00451321
Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.
Thursday, February 11, 2010
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
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.
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.
Wednesday, March 11, 2009
Recent News Items on Curing Type-1
Recent News Items on Curing Type-1
Here are some quick notes on recent progress in human trials to cure type-1 diabetes:
I'm going to post something on Peakman's recent results in the next few days.
Tolerx Adds Europe to Phase 3 'DEFEND' Trial of Otelixizumab
This phase-III human trial has been going on for some time in the US, but they recently expanded it to Europe as well. The goal here is to drug the immune system so that more beta cells survive the immune-self attack. This is a 200+ person trial.
Press release here: http://sev.prnewswire.com/medical-pharmaceuticals/20090310/NE8064810032009-1.html
More info:
http://joshualevy.pbwiki.com/DiabetesCureReadyForHumanTrials#TRX4alsoknownasChAglyCD3byToleRx
http://cureresearch4type1diabetes.blogspot.com/search/label/Osiris
Andromedia (Home of DiaPep227) gets $10 million from Teva
This is the longest running phase-III clinical trial that I know of to cure type-1 diabetes. It has been going on for years, and initially the results were not promising. However, the company stuck with it (even as ownership changed hands from company to company). The most recent news still doesn't look too good to me. They had extended and expanded the trial in the hopes of getting some positive results even when the early results were not statistically significant.
However, another company, Teva, is putting in $10 million so hopefully they know more than has been released to the public, and there is good news in there, somewhere.
News article: http://uk.reuters.com/article/rbssHealthcareNews/idUKLI48804120090218
Diamyd Now has four (or five) clinical trials going at once
By my count Diamyd now has five different clinical trials going all at once:
1. They have a classic phase-III clinical trial for honeymoon diabetics which helps preserve insulin production so that patients use less insulin, and maybe no insulin at all. This being done in the US, and being 300+ patients.
2. They have a "twin" phase-III clinical trial being done in Europe with another 300+ patients.
3. They have extended their previous phase-II trial (to continue to run it for several extra years) to look for longer term effects (both good and bad).
4. They have phase-II clinical trial aimed at both preserving existing insulin production and regrowing new beta cells (a possible non-honymoon cure).
5. They have a phase-II clinical trial aimed at preventing type-1 diabetes by giving the treatment to people at high risk of type-1, but who have not shown symptoms as yet.
Newspaper articles / press releases:
http://drugdiscovery.pharmaceutical-business-review.com/news/diamyd_medical_wins_swedish_approval_for_diabetes_vaccine_study_100309
http://www.msnbc.msn.com/id/29220725/
More info:
http://joshualevy.pbwiki.com/DiabetesCureReadyForHumanTrials#DiamydTbyDiamyd
http://cureresearch4type1diabetes.blogspot.com/search/label/Diamyd
Osiris Therapeutics's PROCHYMAL in the news
This is the same research that Kimberly Wainscoat asked about. Osiris has been running a phase-II trial since mid last year. Their PROCHYMAL treatment has been show safe in several phase-I, II, and even III trials for several immune diseases, so they are trying it with type-1 diabetes. This is an adult (actually self) stem cell treatment. Since safety is established, they went straight to phase-II clinical trials. It appears that they are either ramping up recruitment of patients, or ramping up PR of the trial. Recently there have been very similar "public interest / human face" type newspaper articles on this trial, links below:
http://www8.utsouthwestern.edu/utsw/cda/dept353744/files/519415.html
http://news.cincinnati.com/apps/pbcs.dll/article?AID=2009903100368
More info:
http://joshualevy.pbwiki.com/DiabetesCureReadyForHumanTrials#PROCHYMALbyOsirisTherapeutics
http://cureresearch4type1diabetes.blogspot.com/search/label/Osiris
Joshua Levy
Here are some quick notes on recent progress in human trials to cure type-1 diabetes:
I'm going to post something on Peakman's recent results in the next few days.
Tolerx Adds Europe to Phase 3 'DEFEND' Trial of Otelixizumab
This phase-III human trial has been going on for some time in the US, but they recently expanded it to Europe as well. The goal here is to drug the immune system so that more beta cells survive the immune-self attack. This is a 200+ person trial.Press release here: http://sev.prnewswire.com/medical-pharmaceuticals/20090310/NE8064810032009-1.html
More info:
http://joshualevy.pbwiki.com/DiabetesCureReadyForHumanTrials#TRX4alsoknownasChAglyCD3byToleRx
http://cureresearch4type1diabetes.blogspot.com/search/label/Osiris
Andromedia (Home of DiaPep227) gets $10 million from Teva
This is the longest running phase-III clinical trial that I know of to cure type-1 diabetes. It has been going on for years, and initially the results were not promising. However, the company stuck with it (even as ownership changed hands from company to company). The most recent news still doesn't look too good to me. They had extended and expanded the trial in the hopes of getting some positive results even when the early results were not statistically significant.
However, another company, Teva, is putting in $10 million so hopefully they know more than has been released to the public, and there is good news in there, somewhere.
News article: http://uk.reuters.com/article/rbssHealthcareNews/idUKLI48804120090218
Diamyd Now has four (or five) clinical trials going at once
By my count Diamyd now has five different clinical trials going all at once:
1. They have a classic phase-III clinical trial for honeymoon diabetics which helps preserve insulin production so that patients use less insulin, and maybe no insulin at all. This being done in the US, and being 300+ patients.
2. They have a "twin" phase-III clinical trial being done in Europe with another 300+ patients.
3. They have extended their previous phase-II trial (to continue to run it for several extra years) to look for longer term effects (both good and bad).
4. They have phase-II clinical trial aimed at both preserving existing insulin production and regrowing new beta cells (a possible non-honymoon cure).
5. They have a phase-II clinical trial aimed at preventing type-1 diabetes by giving the treatment to people at high risk of type-1, but who have not shown symptoms as yet.
Newspaper articles / press releases:
http://drugdiscovery.pharmaceutical-business-review.com/news/diamyd_medical_wins_swedish_approval_for_diabetes_vaccine_study_100309
http://www.msnbc.msn.com/id/29220725/
More info:
http://joshualevy.pbwiki.com/DiabetesCureReadyForHumanTrials#DiamydTbyDiamyd
http://cureresearch4type1diabetes.blogspot.com/search/label/Diamyd
Osiris Therapeutics's PROCHYMAL in the news
This is the same research that Kimberly Wainscoat asked about. Osiris has been running a phase-II trial since mid last year. Their PROCHYMAL treatment has been show safe in several phase-I, II, and even III trials for several immune diseases, so they are trying it with type-1 diabetes. This is an adult (actually self) stem cell treatment. Since safety is established, they went straight to phase-II clinical trials. It appears that they are either ramping up recruitment of patients, or ramping up PR of the trial. Recently there have been very similar "public interest / human face" type newspaper articles on this trial, links below:http://www8.utsouthwestern.edu/utsw/cda/dept353744/files/519415.html
http://news.cincinnati.com/apps/pbcs.dll/article?AID=2009903100368
More info:
http://joshualevy.pbwiki.com/DiabetesCureReadyForHumanTrials#PROCHYMALbyOsirisTherapeutics
http://cureresearch4type1diabetes.blogspot.com/search/label/Osiris
Joshua Levy
Friday, June 6, 2008
New Phase III Trial Starts: Otelixizumab from Tolerx
Good news! A new Phase III trial has started to test a honeymoon cure for type-1 diabetes!
You can read about it (from a technical point of view) here:
DEFEND Trial
Basically, this is a CD3 targeting drug, very similar toTeplizumab by MacroGenics. It is only being tested on honeymoon phase diabetics, but remember my hopeful comments on honeymoon cures becoming cures for everyone. This drug has been in phase II trials for a while, as has Teplizumab.
Press Release Reporting this (see the last paragraph)
You can read about it (from a technical point of view) here:
DEFEND Trial
Basically, this is a CD3 targeting drug, very similar toTeplizumab by MacroGenics. It is only being tested on honeymoon phase diabetics, but remember my hopeful comments on honeymoon cures becoming cures for everyone. This drug has been in phase II trials for a while, as has Teplizumab.
Press Release Reporting this (see the last paragraph)
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