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:
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:
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
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/
