But before I do that, I want to discuss the word "vaccine". When I talk to parents or people who have type-1 diabetes, and ask them what the word "vaccine" means, they always say something like "something you give to a healthy person to prevent a disease". And they wonder why anyone who already has type-1 diabetes would care about a vaccine. But in the scientific world, the term "vaccine" means something that changes how the body responds to a specific substance (called an "antigen"). As researchers use the term, a vaccine can cause the body to respond more strongly or less strongly. So from this point of view, a vaccine which causes the immune system to stop attacking it's own beta cells would be very important to cure research.
This symposium was jointly sponsored by JDRF and FastForward which is focused on finding a cure for multiple sclerosis. Both of these are autoimmune diseases (ie. diseases caused by the body's immune system mistakenly attacking a working part of the body). So the idea is to jointly research and promote cures for autoimmunity in general.
There was one piece of bad news about why companies do not invest in type-1 diabetes, and two pieces of good news about why they do:
The bad news: If you've got 50 or 100 million dollars to invest in research, are you going to spend it on type-1 diabetes, or type-2 diabetes (which has about 10 times a big a market)? You are going to spend that money to develop a type-2 drug. Bigger market.
The first good news: Curing type-1 is an "unmet need". That means there is no competition. You make more money if there is no competition, so that is motivating people to research type-1 even in the face of the larger type-2 market. If you enter the type-2 market you have lots of competition (and some of it is really cheap, so it is hard for you to charge a lot for a new drug, if an old one is cheap). However, if you enter the type-1 market, you own it.
The second good news: Type-1 is related to other autoimmune diseases (especially: rheumatoid arthritis, multiple sclerosis, and possibly lupus and others.) So that means that money you put into curing type-1 diabetes might also lead to a cure for these other diseases, and that could be very profitable. A sort of three for one deal on cures. This also motivates companies to put more money into type-1 research.
This leads into discussion of the symposium's magic word: "platform". You might think that a platform is a wooden box that you stand on. I'm a software engineer, and we use "platform" to mean a bunch of software that helps develop new software and can be used over and over again for that purpose. The pharma guys use the word in much the same way that software guys do. A pharma "platform" is a way to speed the development of multiple drugs. Everyone who is working on a drug, talks about their platform. They hope that their development can be used again and again to develop multiple different cures for different diseases. The word "platform" represents the unbridled optimism common to researchers; and the funding opportunity that every venture capitalist, pharma company, and non-profit is looking for. They haven't even started a clinical trial, and are already talking about how they will cure multiple diseases in the future. "Platform" is the pot of gold at the end of the rainbow.
To be a little more specific, two types of platforms were discussed. The first was a common collection of ingredients that you can customize to cure different diseases. Consider this bread analogy: you have a recipe for pecan bread. You try replacing the pecans with almonds, now you have almond bread. You replace them with blueberries and now you have blueberry bread. Your bread is what the pharma guys would call a "platform". You drop in one new ingredient to create a new bread. If your bread recipe is good at this sort of flexibility, then a commercial bakery would be very interested in it, as well as all the "specialty" bread recipes.
Bayhills has exactly this kind of platform: it is a ring structure of several chemicals, one of which is specific to type-1 diabetes. That drug is called BHT-3021 and is targeted at type-1 diabetes. But if you take the same basic ring, and replace the type-1 chemical with a different one aimed at multiple sclerosis, then the drug is called BHT-3009 and is aimed at MS. And so on....
Another kind of platform is a method to find drugs, which you can use again and again on different diseases. Again, to use a cooking analogy, let's say you are looking for a dinner recipe and so you grab a can of chicken soup and pour it over chicken meat and bake it. A week later you grab mushroom soup, pour it over beef and bake that. You now have a "platform" for making recipes. The platform is this: pour a can of soup over a meat and bake it. None of the ingredients are reused (as they are above), but the basic technique is reused. There were a couple of different researchers with this kind of platform at the meeting. Including Apitope and Dr. Mannie (neither in clinical trials as yet).
The second most important word at the symposium was "bio-marker". A bio-marker is a way to do an experiment for cheap. For example, lets say you have a drug and you think it cures type-1 diabetes. Running an experiment to see if it does will take years: you need to make sure type-1 doesn't come back. However, if you had some blood test that told you the person no longer had type-1, then you would not need to follow them for years. You would just need to do the blood test. That blood test would be for a "bio-marker". Something that showed you the drug had worked, but was cheaper, quicker, and easier than seeing if it had really worked. Finding a bio-marker for a disease speeds up ALL research aimed at curing that disease, and it attracts research money to that disease, since research there is less risky.
C-peptide is such a bio-marker for type-1 diabetes, but the pharma guys are always wishing that there were more. It makes research, cheaper, quicker, less risky, and less unknown. It is especially important that the government regulators agree to the use of the bio-marker. If they do, then you can get government approval that the drug is useful, based on the bio-marker: quicker, cheaper, less risky, and you know approval will be granted.
Type-1 diabetes is diagnosed in about 78 thousand people per year in the US and the EU. That is your core market for any new, honeymoon treatment. There are about 2.1 million people who have type-1 diabetes in the US and the EU, so that is your market for any new treatment. At the time of diagnosis about 10%-20% of the beta cells are still working.
Since I focus on clinical trials, for me, the most important presenters were those who had clinical trials underway:
Diamyd (makers of GAD-Alum) expects to have results from the Euopean phase-III trial "this Spring, before the Summer". This study has three branches (people who did not get Diamyd, people who got two injections and people who got four injections). It only includes people within three months of diagnosis. Their phase-II study included people from longer after diagnosis, but the results were not so good for those people, so the phase-III study cut off eligibility at 3 months post diagnosis.
There is also have a small prevention trial in Sweden: 50 kids aged 4-7 who already tested positive to 2 or more different antibodies associated with type-1 diabetes, including the GAD antibody. This study will take years, since they need to wait and see how many of the patients actually come down with type-1 diabetes. This is an example of a the type of trial that doesn't have a bio-marker to speed it along, so it takes a long time to do even a small study.
Bayhill is expecting to be ready to start their phase-II study on BHT-3021 "very soon". They expect to publish the full data from their phase-I study "later this year". They have already published interim phase-I results last Summer, and I'm trying to get a copy of that presentation. Although the FDA did not allow them to enroll children in their phase-I trial, they do expect their phase-II trial to be open to patients under 18 years old. Obviously, this make it easier to complete enrollment. It is also a general sign of safety that the FDA will let you include children in your trial.
One of the interesting things about their phase-I trial is that everyone gets treated eventually. When you enroll, half the people get the drug, and half get a placebo. Each group is then followed for a year, and the research is based on this treated vs. untreated comparison. But then, the people who previously got the placebo are given the drug. The advantage to this (I think) is easier recruitment. Because, in the end, everyone gets the drug. In classic trials, some people don't what to participate, because they are afraid that they will be in the placebo group, and go through all the work, and not get the treatment. This design ensures that: everyone gets the treatment.
Finally, ToleRx (makers of Otelixizumab) were there, but my understanding is that their drug is not antigen specific and therefore would not be considered a vaccine. In any case, I did ask, and was told, that they expected to publish results mid this year from their first phase-III trial. I know their second phase-III trial is about a year behind their first, and both need to be done before they can submit to the FDA for market approval.
Most of the research discussed at this meeting had been done on animals, not people, and I discuss some of it (not all of it), below:
I was reminded (yet again) how enticing animal research is. There were at least three or four researchers at this one symposium who had cured type-1 diabetes in NOD mice. Some of them had cured it in several different animals models, and had performed all sources of confirmatory tests to make sure the animals were permanently cured of type-1 diabetes. It would have been so easy to latch one to one of these guys as the one-true-cure that will lead us all to the promised land. Again and again I reminded myself: don't get too excited about animal cures: they are always a long time and an uncertain result away from a human cure.
The most interesting to me was Parvus. They have licensed Dr. http://www.diabetesincontrol.com/articles/did-you-know/9191-
I particularly liked this paragraph:
According to Teodora Staeva, Ph.D., JDRF Program Director of Immune Therapies, a key finding from [this research] is that only the immune cells specifically focused on aggressively destroying beta cells (or, alternatively, regulating these cells) responded to the antigen-specific nanoparticle vaccine. That means the treatment did not compromise the rest of the immune system -- a key consideration for the treatment to be safe and effective in an otherwise healthy person with Type 1 diabetes.Another interesting piece of animal research was Dr. Daniell, who I've blogged on before:
Dr. Daniell is still looking for funding to start a human trial, and his presentation sounded like a funding pitch. Basically, he has genetically modified lettuce to contain proinsulin, and because proinsulin is wrapped in cellulose, it is not digested, but enters the system of whoever ate it. Why is this important? Because giving proinsulin to NOD mice prevents the development of type-1 diabetes. However, previous researchers have tried to slip proinsulin past the digestive system in people, but this has not succeeded in preventing or curing type-1 diabetes. (As I discuss in more detail in my previous blog entry.) I asked Dr. Daniell about this specifically, and his reply was simple. In previous proinsulin clinical trials the methods used to get the proinsulin past the digestive system were not very good, and he believes the experiments failed because they were not good enough. However, generating proinsulin, naturally wrapped in lettuce cellulose is a much better system. This proinsluiln will get past the digestive system, and therefore will be successful even in the face of the previous failures.
A third interesting research area was Dr. Mannie. He has a platform which he used to create an MS drug, which he has successfully tested in animals. He hopes to get IND paperwork (required to start a human trial) done by 2015 for that drug. So far, he has spent $700,000 on the project. He is confidant that his platform will work for type-1 diabetes as well, if someone gave him a few $100,000s for that project. So, think about this: would developing another cure for type-1 diabetes in NOD mice, be worth $500,000? Should JDRF (or anyone else) put in that money now? Or wait about 6-7 years and see what happens to the MS drug in people?
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.