Monday, February 28, 2011

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

Results from a phase-I Clinical Trial

Back in Sept 2009, Dr. Garg started a small pilot trial of Sitagliptin and Lansoprazole. These are two drugs currently used for type-2 diabetes, but this trial is aimed at using them on people who have type-1 diabetes.  The study was supposed to last about three months, and now they have published some results.
The [treatment] lowered their mean blood glucose by about 12 mg/dL and their A1Cs by 0.27%, and they were able to cut their insulin dose by nearly 10 percent during the treatment period.
They are very happy with the results and plan to start a 120 person study.  You can see the government clinical trials registration here, although it hasn't started yet:

The improvement looks pretty small to me.  They are cheering about 12 BG points improvement?  A quarter point A1c?  10% less insulin?   So, for example, someone who is currently averages a BG of 150 might drop to 138.  An A1c might go from 7.5 to 7.25.  Instead of using 60 units of insulin a day, they might use 54.  I'm underwhelmed, and I hope they get bigger improvements in their phase-II studies.  On the other hand, Lansoprazole is a common antacid and is available over the counter, and while Sitagliptin is prescription, it is also very common.  I don't know the longest clinical trial run with either one of these drugs however.  I'm a little nervous that previous testing of Lansoprazole (the antacid) might just assume you take it once in a while.  I'd be real curious if anyone has seen what happened (even in animals) if you took it every day for a month, a year, 10 years, etc.  Since that is what is envisioned here.  I expect that is what will be learned from the phase-II and phase-III trials.

As far as this blog is concerned, I don't think I will continue following this research, because I think it looks like a treatment for diabetes, not a cure.  But I don't want to be too "down" on this research.  Up until now, different types of insulin has been the only treatment available for type-1s, so this might be the first step to having an array of drugs that help keep BGs more stable.  I know a lot of people would be very happy with a .75 or 1 unit change in A1c, and as a first test, this got 1/3 to 1/4 of the way there.  So maybe further development will get there.


DiaPep277 Fully Enrolls a Small Phase-III Trial

DiaPep277 is a protein design to help train the body's immune system not to attack it's own beta cells.  It was the first treatment that I know of that started phase-III clinical trials, and has been in them for years.  There were two different phase-III studies underway, both about 300 people.  (Remember that for US or EU approval new treatments generally require two phase-III studies of about this size.)  However, the news story below is about a smaller "follow on" phase-III study with 40 people.  This study will follow people for 2 years after they were already part of the phase-II study.  It is looking at longer term safety/effectiveness issues.  Since it is fully enrolled, we "just" need to wait 2+ years for the results.  Of course the results from their mainline phase-III trials matter much more.

Clinical trial:

One Scam Cure and One Fringe Theory
Note that both of these guys cite Dr. Faustman's work, but are totally separate from it.  One of the "tricks" of scientific scams, is that it helps to cite real research, as part of your fraud.  So the fact that Drs. Arnim and Broxmeyer are citing Dr. Faustman says nothing about Dr. Faustman's work.

Ulrich von Arnim
If you ever wanted to know what a type-1 diabetes cure fraud would look like.  Here is your chance:
And here is the news coverage.
I'm not worried that this guy might have really cured type-1 diabetes: he's been in jail for two years for fraud, and has an arrest warrant waiting for him in Germany.  But it is interesting to look at his web site.  If that was your only source of information, you would think it was real.  The only tip-offs that I saw were these:
  • If you look at the "clinical trial registration" number column, I can see that those are not European clinical trial numbers.  Nor are they American numbers.  I think they are European patent numbers (and patents are not the same as clinical trials!)  Also the first row that says "(pre-study)" so has no clinical trial number.  That's wrong: if they used people, they gotta have a clinical trial.  There are ethical and legal issues if they don't.  (It's possible that things were different in 1990-1992, but I don't think they were that different.)
  • The second issue was the number of people "cured".  He claims to have cured about 14,000 people.  Now, there are about 1.5 million people with type-1 diabetes in the EU, so he has cured about 1% of them.  Already.  And we've never heard from even one of his patients.  Sounds nuts to me. (And he claims to have cured 1000s of people as long as 20 years ago, and no one has talked about this?)

Lawrence Broxmeyer
This guy has a fringe theory, or maybe a quack theory, that diabetes is caused by Tuberculosis (TB).  Actually, he has a lot of theories that a lot of different diseases are caused by TB.
If you believe this stuff, then it's obvious why a TB vaccine (like BCG) would cure type-1 diabetes.  He conveniently ignores the fact that giving BCG to people with type-1 diabetes does not cure them.  Nor does it prevent type-1 diabetes.  (In five or six previously completed studies.)

Random Reading / Listening

If you have a CD player in your car, I recommend a recorded lecture called "What is Wrong with Cloning?" by Dr. Arthur Caplan.  (The Sunnyvale, California, USA library has a copy.)  It is 1/3 a discussion of ethics, 1/3 the science of cloning and stem cells, and 1/3 stand-up comedy.  I have never laughed so hard while learning so much.  It's published by The Great Lecture Library.

This University PR piece:
describes three different clinical trials all being run out of UCSF by Dr. Steve Gitelman.
You can search my blog site for "Gitelman" to see previous coverage of these trials.

You might want to also look at this data, about longer life spans for type-1 diabetics dx recently vs. dx in the 1950s:

Reminder About The Blog
This blog generally only covers research results.   Occasionally related topics are discussed.   However, I generally don't discuss funding issues, stock issues, new hires (such as presidents, new board of director members, etc.)  patient issues, etc.  These are all news worthy, but they are not the kind of news that I cover here.

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. 
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Wednesday, February 23, 2011

Chance of FDA Approval

Long ago, one of my first blog postings described the "research funnel".  How a drug went from animal tests through three phases of clinical trials and was eventually approved (and how drugs could fail at each step in the process).  If you haven't read that posting, it contains a lot of useful background information on how drugs get approved in the USA:

I used the best data I could find for that post, but I'm very happy to say that Biotechnology Industry Organization (an industry trade group) and BioMedTracker (a company which collects data on drugs in development) have published some much better data on success rates for US FDA approvals.  Their data set is much larger than what I had back then.  And it is interesting! At least to me :-)

The study was conducted from 2004 through 2010 reviewed more than 4,000 drugs from companies large and small and both publicly traded and private.  But NOT university or non-profit research.

Major findings about the process right now:
  • The overall success rate (all the way through successful FDA approval) for drugs moving from early stage Phase I clinical trials is about 9%.  For phase-II it is 15%, for phase-III it is 44%.
  • 63% of drugs in Phase I testing advanced to Phase II
  • 33% of Phase II drugs made it to Phase III
  • 55% of the drugs that made it to Phase III testing filed for approval applications.
  • 80% of the drugs that filed for approval gained eventual approval (only about half were approved on their initial FDA review)
  • Biologics had a 15% chance of going from Phase I through to FDA approval, compared with a 7% success rate for traditional small molecule chemical drugs. A biologic is more complex than a simple drug.  It is generally something derived from a living organism.  For example, a purified microorganism or specially treated or processed blood or tissue would be a biologic.  BCG, cord blood, and ATG are biologics that are being tested on type-1 diabetics.  
  • The highest overall success rate from Phase 1 through likelihood of approval was for infectious diseases, such as hepatitis and HIV drugs, at 12%.  Next was endocrine system drugs, featuring [type-2] diabetes treatments, at 10.4%.  And then autoimmune diseases, such as rheumatoid arthritis, at 9.4%.
  • Overall success rates from Phase I to FDA approval is nearly 9%. This number is comprised of lead and secondary indications. When separated, lead indications have close to a one in seven rate of approval and secondary indications have a rate of one in 30.  This was seen in all phases of clinical development as well as in all disease areas. 
  • The study also shows that large molecule drugs are twice as successful in gaining approval than small molecule drugs.
Major findings about changes in the process:
  • Overall success rate for drugs moving from early stage Phase I clinical trials to FDA approval is about 9%, down from one in five to one in six seen in reports involving earlier years.
  • The 80% approval rate (for drugs that submitted applications), is down from 93% seen in early studies.

Here are some very rough calculations:
There are currently about 15 phase-I trials with a 9% chance of eventual approval   (1.35 total)
There are currently about 10 phase-II trials with a 15% chance of eventual approval (1.50 total)
There are currently about 3 phase-III trials with a 44% chance of eventual approval (1.35 total)
So, a reasonable estimate is that out of the current crop,  4 drugs will eventually be approved.  It will be very interesting to see how this plays out over the next few years.

But with two serious limitations:

First, The study above only included commercial company's drugs.  it did not include drugs being researched at universities.  I would assume that university research is far less likely to eventually be approved than commercial research. (There are at least two reasons for this: first, universities should be more experimental and less worried about practicle applications, and second, they don't have the resources to push treatments and commercial companies do.)  Since several of the current clinical trials are university research, they are less likely to end up being approved.

Second, most of the current crop of treatments in clinical trials are not cures.  Indeed, only one (Burt) has kept people free of external insulin for 4 years.  That is a phase-I trial, so I think it is reasonable that we are going to need about 10 more treatments in phase-I that actually cure people (or get close) before such a cure will become generally available.

I know that many people want to spend a lot of time and resources investigating drugs that are already approved, for some other purpose, in the hopes that they will cure type-1.  This study shows the dangers of such a focus, since those are the secondary indications that have the much lower success rate.  It turns out that most treatments only work on one thing, so if you try to use them for something else, you chance of success goes way down.  (Even if it is cheaper and quicker.)

Also, it is interesting to me that more complex treatments have higher chances of eventual approval.  Biologics are more complex than drugs, but have a greater chance of approval.  More complex molecules are more likely to be approved than simple ones.  My guess is that because these are more expensive to develop, companies only push the very best of them.  Or maybe all the simple cures have already been productized, and only the more complex ones remain.

If you work in the pharma industry, or if it is important to you, I strongly suggest that you look at this PDF file.  It is thick with information:
News reports:;_ylt=AgsEciuYx.Hb5aUFo.oOX0gPLBIF;_ylu=X3oDMTJ2OGI2aGpzBGFzc2V0A25tLzIwMTEwMjE0L3VzX3BoYXJtYWNldXRpY2Fsc19zdWNjZXNzBHBvcwM4BHNlYwN5bl9hcnRpY2xlX3N1bW1hcnlfbGlzdARzbGsDc3VjY2Vzc3JhdGVz

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. 
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Tuesday, February 8, 2011

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

Rilonacept Starts a phase-I Clinical Trial

About six months ago, I blogged about three clinical trials which had not yet started, but were expected to start "soon".  Now the Rilonacept study is actually starting. 

This drug has not previously been tested on type-1 diabetes, but is already approved for other diseases (since 2008 to treat CAPS) under the name Arcalyst.  It is currently in use in about 12 phase-II and phase-III clinical trials for several different inflammation based diseases, especially Gout. It is an IL-1 inhibitor, and IL-1 is known to be involved in the destruction of beta cells in people with type-1 diabetes.  The hope is that this treatment will result in a longer, stronger honeymoon, and may result in long term improvements in A1c (such improvements might lead to fewer serious complications years or decades down the road).  This is the third treatment targeting IL-1 that I'm following. Others include Anakinra and Canakinumab.

The study will enroll 15 patients, all of who will be treated with Rilonacept (no placebo group).  To enroll you must be over 16 years old, within 5 years of diagnosis, and still producing some C-peptides (> 0.2 nmol/L) in response to food. These people will be followed for six months, involving five clinic visits, and it is hoped the trial will be complete by June 2012.  The treatment is weekly injections (under the skin, like insulin).  They will be looking for general safety issues, as well as effectiveness (A1c, C-peptides, and insulin dose).  This is NOT a honeymoon only trial, by my definition.

This is being run out of Children's Medical Center (Dallas, Texas, USA):
Principal Investigator: Perrin C White, MD

If you are interested in participating, send Dr. White some email.  Don't worry about your C-peptide production.  If you meet the other criteria, they will test for that.

It is interesting to me how much the design of this clinical trial has changed in the last six months.  You can compare what I'm writing now, to what I wrote back then:
to see the differences.

Clinical Trial Record:

Thanks very much to Dr. White for providing information about this trial.

News on the Animas Artificial Pancreas

News article on Animas's Artificial Pancreas.  Obviously, I'll be a lot more interested when it actually starts a clinical trial:

Background reading on Artificial Pancreases in General

This paper is a little dry and a little dense, but it gives a good summary update of where we are, and the lead author (Hovorka) is actively involved in AP research:

Reminder About The Blog
I'm not a doctor or research professional of any kind.  I can not provide medical advice, because I lack the knowledge.  I don't recommend one clinical trial or another.  I think that any discussion about participating in a clinical trial must be held between you and your medical team.  I know not everyone has a doctor they trust, and I'm sorry about that, but I can't give you advice on which clinical trial you should be part of, or avoid. 

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.
To Get as Email Join here: