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

This posting contains some bits and pieces of interesting news.

A Phase-II Abatacept Trial to Prevent T1D in At-Risk People Finishes Recruiting 

You can read my previous postings on Abatacept here:
https://cureresearch4type1diabetes.blogspot.com/search?q=Abatacept
Abatacept is a treatment that prevents T-cells from becoming activated.  Presumably, for type-1 diabetes, it works by blocking the "bad" killer T-cells from activating.  This drug is already approved for use in rheumatoid arthritis when other treatments have failed, and is marketed as Orencia.

This is a large (212 person) trial started in 2013, and recruited it's final person in February 2020.  Since they plan to collect data from each person for at least a year, this trial is likely to finish in February 2021.  The goal of this trial is to see if Abatacept can be given to people before they are diagnosed with T1D, and prevent or delay the onset of the disease.  The people enrolled in this study have tested positive for two or more autoantibodies, so they are almost certain to be diagnosed with type-1 diabetes sometime in the next 10 years.

History and Discussion

Abatacept has already been tested on people with T1D in their honeymoon period, and the results were that people treated with Abatacept continued to generate about 50% more of their own insulin, than those not treated.   The amount of insulin generated years after diagnosis is pretty small, so the actual difference is half of a tiny number.  One way to view these results was that Abatacept delayed the "end of honeymoon" by 9.5 months.  Someone who got the drug generated the same amount of insulin 36 months after diagnosis as someone who did not get the drug generated 27 months after diagnosis.

So this result is similar to the recently published Teplizumab results, although the Teplizumab results were a little stronger.

Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT01773707

Phase-I Clinical Trial of Substance P Is Over Two Years Overdue

Substance P is a peptide (a part of a protein) which is used by several different organs and for several different purposes.   Research done in the early 2000s found that a specific type of neuron (called "TRPV1(+) pancreatic sensory neurons") control islet inflammation and insulin resistance. Removing these neurons from NOD mice prevented diabetes from developing.  Injecting NOD mice with Substance P, which affects these neurons, has increased beta cells in mice, and also lowered inflammation.   This clinical trial tested this same treatment in people, rather than mice.

The trial started in 2016 and was expected to finish in 2017.  The clinical trial record has not been updated since 2016, and I cannot find any published data from this study or the company that sponsored it (Vanilloid Genetics Inc).  Twice I've sent email to the researchers running this study, and I have gotten an "on vacation" email back from one of them, so I know they are still at the University where this research was done, but I have not gotten any other reply.  I have not found any corporate email info for Vanilloid Genetics. 

So therefore, I'm going to remove this study from my list of active studies.  If I ever see positive results, then I'll put it back on.

Clinical Trial Registry:  https://www.clinicaltrials.gov/ct2/show/NCT02820558

PROCHYMAL® (Adult Stem Cells) for the Treatment of Recently Diagnosed T1D

Way back in 2012, I reported on an unsuccessful Phase-II- study of PROCHYMAL (adult stem cells) by a company called Osiris.  However, in March 2020, the clinical trial record for that trial (now completed for 8 years) was updated.  The changes made were all small, and I would describe them as "cosmetic".  I don't know what this means.  If it means anything at all.  But it is unusual for the clinical trial record for a trial completed so long ago to be changed.

Clinical Trial Record: https://www.clinicaltrials.gov/ct2/show/NCT00690066


Changing Terminology: At-Risk Instead of Presymptomatic

In the past, I have used the term "presymptomatic" to describe people who have two autoantibodies, but none of the classic signs of type-1 diabetes.  TrialNet has published data over the last few years that shows that just about all of these people will have symptoms of T1D within 10 years.  Therefore many researchers consider that people with two autoantibodies, but no other symptoms, really do have T1D, it is just that they don't have symptoms, yet.  So I used the term presymptomatic to describe the studies being done on these people.

But "presymptomatic" is a mouth full, and it is not a natural sounding word.  Also, people who don't inject insulin and don't count carbs don't think of themselves as having T1D at all.  So therefore, I'm going to start using the term "at-risk" to refer to these people, and the clinical trials that enroll them.  I think it is a more natural English phrase to describe people who are not showing symptoms yet.  

Joshua Levy 

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Possible Cures for Type-1 in the News (late Sept-2012)

Prochymal Failed Phase-II Trials

I missed this, when it was published back in May, but luckily Kelly Close (of Close Concerns, who publishes DiaTribe) reported on it:

At 1 year, intravenous infusions of Prochymal were reportedly well tolerated, with no differences in adverse event rates between the Prochymal and placebo groups. 

With regard to efficacy, no significant differences in stimulated C-peptide levels were observed between the two arms (the primary efficacy endpoint), although a trend towards fewer hypoglycemic events in the Prochymal arm was observed. 

A full analysis will be performed following an additional year of follow-up (for a total of 24 months)

My translation is this:

• The trial failed its primary endpoint.
• The researchers are trying to be optimistic about a small, vague result in one of the secondary endpoints.
• The study will get more data after another year, and they are hoping for better news.

Obviously, I'm hoping for better news next year, too.  But I'm not expecting it.

Scientific Press Coverage: http://onlinelibrary.wiley.com/doi/10.1111/j.1753-0407.2012.00197.x/full

DiaTribe is a free on line newsletter (http://www.diatribe.us/), which is is a great source of info on diabetes research, technology, etc.

NI-0401 by NovImmune Failed a Long Time Ago

Years ago a company called NovImmune started a phase-II trial for their drug NI-0401 aimed at type-1 diabetes.    After that, no news.  This drug was targeted at CD3, and all the other CD3 drugs failed, so I always assumed this one had, as well.  But there never was any news, and I never saw an official announcement.  However, NovImmune updated their entire web site, and NI-0401 is still there, but diabetes is not listed as a target at all.  Also, I found a European clinical trial registry, which showed that the long ago study had been canceled just months after it started.

So NI-0401 is dead, as far as I'm concerned, until I hear otherwise.

European clinical trials registry:
http://apps.who.int/trialsearch/trial.aspx?trialid=EUCTR2009-012988-34-AT
https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-012988-34/AT

Corporate web site:
http://www.novimmune.com/products/ni-0401.html

DiaPep277 by Andromida is Fully Enrolled

This is the only treatment that I'm following that is currently in phase-III trials.  The results from previous work suggest it might be a "longer, strong honeymoon" type treatment, rather than a cure. they have already finished one phase-III trial, and this is their second.  The FDA requires two, so when this one completes, if it is successful, they will be ready to move into "marketing approval" phase, which takes a year or two.

Why is this important? For two reasons.  First, because it is now possible to predict when they will finish collecting data.  (Since this study gathers data for 2 years, it will finish about Sept 2014.) Second, because much of the uncertainty that surrounds clinical trials, is involved with recruiting participants.  It is often unclear how hard it will be to recruit people, and long it will take.   But that this point, all that cunertainty is behind the researchers.  From now on, it is just gather data, then analyze data, and then publish data.  Researchers have a lot more control over those later stages, then over recruiting people in the first place.

News: http://www.marketwatch.com/story/andromeda-biotech-successfully-completes-patient-recruitment-in-phase-iii-confirmatory-trial-for-its-lead-drug-diapep277-for-type-1-diabetes-2012-09-12

How Doctors Weigh Clinical Trial Funding

This was a very interesting study of doctors.  Basically, the researchers gave doctors summaries of research results.  These summaries breifly described a study's results, methodology, and source of funding.    The doctor was then asked questions to determine how much they trusted the results, and how willing they were to proscribe the medicine being tested, based on the trial.  (The research described was fictional, so the doctors did not have any prior knowledge of the drugs in question.)

Here is a summary of the results:

The study found that physicians weighted their assessment of the rigor of a trial based on pharma funding, and that they were half as willing to prescribe those disclosing industry sponsorship as they were those disclosing NIH funding, regardless of methodological rigor.

Discussion

I think these results are good in two separate (but related) ways.  First, they suggest to me that doctors properly "discount" clinical trials funded by industry.  Second, it suggests to me that when a doctor recommends a treatment, they are already taking into account who funded the studies suggesting its use.  The recent problems with pharma PR guys "ghost writing" research articles, and withholding placebos from some researchers has made some people nervous about the accuracy of studies they do fund.  I think it is proper that doctors are also nervous, and I feel good that the average doctor in the study took into account the funding source of clinical trials they read about.

Interestingly, the researchers who ran this particular trial are a little unhappy about their own results.  They seem to think that when comparing two studies, if the methodologies are equally rigorous, that the results should be weighted the same, no matter who did the funding.  They are specifically worried about doctors undervaluing what the researchers consider large scale, well designed, industry funded studies.   I disagree.  I think the prescribing doctors are doing the right thing by undervaluing (or "discounting") equally rigorous studies that are funded by industry.  I view the attitude of these researchers as being very "old school" (and in this case, out of date).  Sure, in the 1950s the idea was that rigorous trial methodology and peer review together were all that was needed to ensure accurate results.  The idea was that the scientific method was so good that who funded the trial was not critical to the quality of the results.  But 60 years later, I don't think that's the consensus opinion.   Now we know that quality starts with good methodology and peer review, but those alone are not enough.

News coverage: http://www.mmm-online.com/docs-downgrade-results-of-pharma-funded-clinical-trials/article/259981/

Symlin as a Treatment

Not for a cure, but of interest, are the results of two studies testing symlin in type-1 diabetics.  Only one was placebo controled, and it found:

analysis of 248 patients from a 29-week, placebo-controlled study, measurements in the normal range based on ADA criteria increased from 37.3 percent to 43.9 percent for SYMLIN-treated patients (n=115), compared to an increase from 38.2 percent to 40.9 percent in those receiving placebo (n=133). The percent of measurements in the normal range based on AACE criteria increased from 22.6 percent to 27.8 percent for SYMLIN-treated patients compared to an increase from 24.1 to 25.0 in those receiving placebo. The percentage of readings in the hypoglycemic range remained relatively stable.

Discussion

I'm not sure I'd take a second injection with meals (or a first injection for pump users) for that level of improvement, but it's still interesting.  I also think that A1c improvements would be a better measure of goodness than % inside of guidelines.   But you gotta start somewhere.

Maybe we'll end up with a tri-treatment artificial pancreas.  It will dose insulin for highs, glucagon for lows, and symlin with meal boluses.

Press Release: http://www.businesswire.com/news/home/20120609005027/en/SYMLIN%C2%AE-Helped-Patients-Type-2-Type-1

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. My blog contains a more complete non-conflict of interest statement.
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

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

Osiris Therapeutics has started a Phase II trial

Osiris Therapeutics has started a Phase II trial of their Prochymal cure for type-1 diabetes. This is an adult stem cell based cure, which has already completed Phase I and II trials and is undergoing Phase III trials targeting other immune diseases, such as Crohn's and Organ Rejection, etc. I think it is being tested on 6 or so different diseases right now. The company's description is this: "Prochymal is a preparation of mesenchymal stem cells specially formulated for intravenous infusion. The stem cells are obtained from the bone marrow of healthy adult donors."

The trial is 60 people, all within 16 weeks of initial diagnosis. It started in June 2008 and is expected to end in June 2010. The study is being done in Tennessee, and is partly funded by JDRF. Here is the company's description: "The design will be a double-blind, placebo-controlled trial at multiple sites with a target enrollment of 60 patients, and patients will be randomized to either Prochymal or placebo at a 2:1 ratio. The primary endpoint of the trial will be the measurement of C-peptide produced during a Mixed Meal Tolerance Test in patients treated with Prochymal, compared to those receiving placebo."

As far as I know, this is the first Phase II human trials for any stem cell based cure for type-1 diabetes. So it represents a whole new approach to a cure, into Phase II trials. Very good news.

For more information:
http://www.medicalnewstoday.com/articles/112956.php
http://www.osiris.com/clinical_trials_prochymal_t1d.php
http://www.osiris.com
http://clinicaltrials.gov/ct2/show/NCT00690066