Diamyd : Prevention vs Intervention, why should we care?

Long time since last entry and some news regarding the Diamyd GAD65 trials to prevent or improve Type 1 Diabetes.

Today we got news that the prevention trial mentioned before has started and three children have been treated. Why is this important and what differs this trial (prevention) from the other trials (Phase III Intervention)?

We have very good ways of screening children for Type 1 Diabetes. With that information Diamyd is trying to see if early injections with GAD65 will not only preserve beta cells but actually stop the disease before outbreak. Prevention trials take 5+ years to give good enough data, but just because it takes a long time doesn't mean it's not worth doing. Phase III Intervention trials are running in parallel, both in Europe and in America (actually three separate trials are done in America).

We have also news that the American part of the Phase III trial is reducing the minimum age to 10 years (from 16 years). This will reduce the time it takes to enroll patients.

Looking at older plans, Diamyd was planning to have enrolled all 640 patients in the two Phase III trials. As usual delays are a part of this kind of research and now we are looking at end of 2009 for the last patient to be enrolled (delay of 6 months).

Overall it looks good! Safety is the key here, and a safe drug that works a little is 10 times better than a dangerous drug that works good (well not always, but while treating children!!). So we are still waiting for Phase III data, planned Q1 2011, fingers crossed.

Have a nice summer!

Diamyd trials update

Much has happened in the last few months.
Here is a picture to illustrate the trials currently ongoing and when they (if data is available) will present the results.

As you can see, Phase III results are expected in fall 2010, and FDA/EMEA approval (if granted) is expected to take 6-9 months.

Click on the image to make it larger.

Trialnet starts trial using Diamyd vaccine

Trialnet will start the Diamyd Phase II trial at 15 clinics in the US.
This study will include 126 patients and add to the data planned to be received by the Phase III trials currently ongoing in the US and Europe, and the Combination trial mentioned earlier also supported by the NIH/NIDDK.

The group of 126 patients will be placebo controlled and given 3 injections of either GAD65 or Placebo. To be included in this trial you have to be newly diagnosed (3 months) and be within 16 - 45 years old.

After a while the age requirement will drop to 8 years and at the end of the trial probably even down to 3-4 years of age. This acceptance of very low ages is made to accommodate for the Trialnet prevention trial planned to start this year.

Recruitment is planned to take 6-9 months and first results can be expected in the first half of 2011 (we have Phase III results in fall of 2010).

Trialnet Chair Dr Skyler has the following to say:
"We are pleased to announce the launch of this trial, which will employ state-of-the-art technology to investigate the vaccine's modulation of the immune system to induce immune tolerance in type 1 diabetes. We look forward to studying the vaccine's effect and mechanism of action at TrialNet's 15 clinical centers in North America,"

This trial is another step on the way to secure that Diamyd (GAD65) is effective in slowing down or completely stopping the auto-immune reaction which destroys the beta cells.

Safety
VERY important to hear that FDA will allow younger children to try out this drug. Don't get me wrong, i'm not for testing unproven drugs on children, but for me this proves that Diamyd indeed has a strong safety profile. Compare to for example to TolerX, DiaPep and Macrogenics (teplizumab) who all have a range of side effects.

In less than 2 years we will get first data from Phase III trials. Then more data will continue to drop in as the patients are followed for a few more years. If results in Phase III trials looks as good as Phase II results published in NEJM, the drug can be on the market early 2012.

I'm hopeful and glad that we have this range of trials so results will be definitive.

If you want to read about other possible cures for T1D, I recommend cureresearch4type1diabetes by Joshua Levy.

Second Diamyd type 1 diabetes prevention trial started

Today the second Diamyd (GAD65) prevention trial was approved by the Swedish medical authorities.

It will be conducted at Lund University hospital in Sweden.
The trial will include 50 children from 4 years of age, randomized and placebo controlled.

The fact that children as young as 4 years old where approved for this trial is good evidence on the amazing safety profile Diamyd (GAD65) has shown so far.

"To stop the immune attack on the insulin producing cells in type 1 diabetes may be easier the sooner it is done in the disease process", says Professor Åke Lernmark, at Lund University, Sweden. "It is like steering a big boat away from a threatening collision. The sooner the course is changed, the better. A timely change in the course of the disease - no insulin injections - that may be this century's contribution to curing autoimmune diabetes. Last century's contribution? Insulin injections!"

Now we are only waiting for Trialnet to also start the US prevention trial, using identified high-risk patients identified in the Natural History Study.

Source:
Diamyd Press release

First Diamyd type 1 diabetes prevention trial started

The first of three prevention trials using Diamyd have now started at the Oslo Diabetes Research Center in Norway.

The study will include 90 high risk patients for type 1 diabetes, and 60 newly diagnosed. The really interesting part of this study will be the tissue samples from the pancreas which according to the press release will provide insight in how Diamyd reduces the destruction of the beta cells.

"This is a major step in diabetes research. We have never previously studied what actually happens to the beta cells during onset of type 1 diabetes," says Professor Knut Dahl-Jørgensen who will lead the study. "In addition to studying how the Diamyd® vaccine affects the insulin producing cells in people at high risk for developing type 1 diabetes, as well as how Diamyd® preserves the insulin producing capacity in recent-onset patients, we will specifically investigate whether type 1 diabetes may be caused by viral infection."

No further information is available on how long the trial will be and when we can have the first data points.

It will be very interesting to see the results from the tissue samples of the pancreas.

As mentioned earlier, I expect two additional prevention trials to be started during this year. One run by NIH / Trialnet and the other by Lund University, Sweden.

More information:
Diamyd press release

Combination trial aimed at regenerating beta cells

I have previously advocated the use of multiple drugs in order to try and cure Type 1 Diabetes. Diamyd which is trying to stop the autoimmune reaction against the insulin producing beta cells could be combined with drugs that stimulate the generation of new beta cells, or with beta cell transplants.

Today we found out that the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) have started, and is recruiting 164 patients in a trial at Bethesda, Maryland (USA). The trial will only treat newly diagnosed (0-4 months from onset), but the results could benefit everyone. If the body still regenerates some beta cells (common idea today within the research community), and you stop the autoimmunity (using GAD65 - Diamyd) as well as increase the regeneration, this could help even already diagnosed Type 1 Diabetics.

This trial is combining GAD65 (Diamyd) which stops or delays the autoimmune reaction towards the beta cells, Sitagliptin a DPP-4 inhibitor used for Type 2 Diabetes and Lansoprazole a proton pump inhibitor.

Both Sitagliptin (Merck, 2006) and Lansoprazole (1995) are approved drugs by the FDA.

Press release from Diamyd
Link to trial information, and here.

If you can't cure it, prevent it!

Lately there has been some news from a unexpected source regarding the upcoming Diamyd (GAD65) prevention trial. We have been expecting news on the NIH TrialNet funded prevention trial expected to start in mid 2009, instead news from two independent sources have said to be interested in starting one prevention trial in Scandinavia and one in Sweden, pending approval from the medical agencies.

Now we are awaiting three prevention trails with Diamyd (GAD65) to be started in the first half of 2009.

1.
NIH TrialNet, USA
Lead: Jerry Palmer / Ellen Leschek
Status: Planned, waiting FDA approval
Start date: mid-2009

2.
Lund University, Sweden
Lead: Helena Elding
Status: Approved from ethics committee, pending approval from medical agencies
Start date: mid-2009

3.
Scandinavian Prevention Trial
Lead: Unknown
Status: Unknown
Start date: 2009

Why prevention? Well it looks like the largest problem is not to halt the beta cell destruction, but to regenerate the beta cells. So stopping the assault before all or any beta cells have been destroyed is the key point here (until we have solved the beta cell regeneration problem).

BIG problem with prevention is that 90% of all type 1 diabetics have no relatives and no real reason to suspect that they might be at risk. You cannot simply vaccinate the whole population (well you could, but you wouldn't because it's not practical/safe). The three prevention trials above will solve this in slightly different ways. NIH TrialNet will take patients with high risk from their Natural History Study. The Swedish trial from Lund University will use its database of all children born in southern parts of Sweden (ABIS) to pick the children with high risk (2-3 antibodies).

It's still hard to see how this will play out. So far all prevention trials have more or less failed. Is there any reason to be optimistic? Maybe. The Diamyd vaccine can either not work at all, delay the outbreak of type 1 diabetes, or fully stop the outbreak (cure). No one can claim to know what the outcome in these trial will be, since then you wouldn't have to spend years doing them.

Of course it's the effect seen at newly diagnosed (Phase II trial) which has prompted these trials. You also have to note that the sub-group which really benefited (diagnosed <3 months) was only 4 individials. Now Phase III trials with 640 patients will try and verify those results.

The trials are likely to last for at least 5-10 years. They will probably be read yearly and results should be visable after 4-5 years depending on the group size.

So who is this for, people who already have the decease will not benefit, and people who doesn't know they are at risk won't know to care. I would say this news is mostly beneficial to families who know that their children are at a greater risk (siblings/parents/cousins already have the decease). They might have the possibilty to reduce or eliminate the risk by a simple vaccination, if it proves to work.

Safety is the word! Since vaccination will probably mean that 90-95-99% of all people receiving the drug won't need it, it has to be safe! Sure a sick kid might accept getting the flu and being at a hospital for 1 week if it improves his diabetes, but a healty kid will for sure not, and should't have to. The absence of side-effects is the important silent benfit of Diamyd (Gad65) (So far!).

Too good to be true some might think, and after 30 years of failiures I can't blame you. But what more can we do than to support research and hope it works. After all, the last 10 years of medical research have been one break through after another. Time for Diabetes now.

Will a successful vaccine against type 1 diabetes kill off all research in a cure to current diabetics? This fear is something we as a community must address and make sure that the research never stops.