Diamyd Medical, Working to Cure Type 1 Diabetes

Diamyd : Prevention vs Intervention, why should we care?

2009-06-22T17:23:00.003+02:00

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

2009-03-15T10:36:00.002+01:00

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

2009-03-11T17:38:00.003+01:00

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

2009-03-04T11:12:00.003+01:00

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

2009-02-13T12:40:00.004+01:00

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

2009-02-05T14:28:00.006+01:00

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!

2008-12-22T20:56:00.003+01:00

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.

No beta cells left, you aren't forgotten

2008-11-29T15:31:00.004+01:00

Many, not to say most type 1 research focus on newly diagnosed diabetes. Because the drugs or therapies focus on preserving the beta cells you have left, not being able to do anything about creating new ones.

However in recent findings Susan Bonner-Weir, Ph.D conclude that beta cells not only regenerate by division of existing beta cells, but may also be created by stimulation of the pancreatic duct cells.

This may lead to a therapy where you stimulate the pancrea to create beta cells. The newly created beta cells are protected by injections of Diamyd GAD-Alum.

There is still a long way to go, but the promise of combination therapies might be the solution for all, not only newly diagnosed.

The news article describing this is linked here.

What is a real cure for T1D

2008-10-26T20:08:00.003+01:00

The word Cure is getting thrown around a lot so it's reasonable to ask the question: What is a real cure for Type 1 Diabetes?

Diabetes is not the same for everyone, which leads to the conclusion that a cure for one person might not be applicable for someone else. Since Diabetes Type 1 (T1D) is a autoimmune decease stopping the autoimmunity should be the first course of action, either through immunosuppression (TolerX, MacroGenics), encapsulation (LCT) or immunotolerization (Diamyd).

Once the autoimmunity is stopped you can consider recreating the insulin producing beta-cells. This is still a major dark cloud and the reason why many (if not all) Phase III trials only include patients close to diagnosis and with remaining beta-cell mass. That way stopping the autoimmunity will in theory be a cure if the patient has sufficient beta-cell mass. So far no drug has proven to completely stop the autoimmunity, only to slow it down.

Lets have a closer look at the different approaches.

immunosuppression
Since it's all about suppressing the T-cells your body will be less resistant against infections and fever/flu-like symptoms are common. T1D often hit young children, and giving immunosuppressing drugs to children might not be taken lightly by both doctors and parents.

encapsulation
Transplanting islets and beta-cells is done and will work as a regular organ transplant. The risks of only transplanting the islets are smaller than a complete pancrea transplant. Even with immunosuppression drugs the new beta-cells will be a target for the immune system and soon get killed of. This is where encapsulation of the islets comes in to the picture. The islets will be protected without immunosuppression. This will work for "old" diabetics since there is no pre-requirement on any beta-cell function. Large downside is the amount of human islets available for transplants (LCT solves that by using pig islets), and the cost of treatment which might make this unavailable for poorer countries.

immunotolerization Can you teach the immune system not to kill your beta-cells? This is the way common vaccines work and by exposing the immune system to small quantities of the antigen you might turn off the autoimmunity. Diamyd works by exposing the body to one of the major auto-antigens in T1D, GAD65. Diamyd will not regenerate any beta-cells, so unless the body can regenerate beta-cells when the autoimmunity is cured, Diamyd will only work for diabetics with remaining beta-cell mass. Not all diabetics have auto-antibodies against GAD65, and if you don't you are excluded from the Diamyd treatment.

Hopefully within a few years (2011 for Diamyd), some therapies will start to become available. Some years later combination therapies will start to emerge and soon the cure(s) everyone is waiting for will eventually become available. Many have heard this before, a cure will soon be here, but we now live in the age of medicine with advances not thought possible.

Regarding newly diagnosed and pre-diabetics vs older diabetics, the first group will be the first to have a therapy available. Simply because they still have beta-cell mass left.

Two other large areas of interest are Stem Cell research and artificial pancreas. More about that later. I hope you have a nice day!

Diamyd published in New England Journal of Medicine

2008-10-08T19:52:00.010+02:00

Diamyd (GAD65) is published in the New England Journal of Medicine.

It's the 30 month followup phase II results on Juvenile Type 1 Diabetes which was very successful and is in our minds the most promising treatment towards a cure for newly diagnosed and LADA patients.

Diamyd is currently recruiting in Europe and USA for two Phase III trials.

Link to article (GAD Treatment and Insulin Secretion in Recent-Onset Type 1 Diabetes).

Another article mentioning Diamyd (GAD65) Immunotherapy on Trial for New-Onset Type 1 Diabetes.

Trials Update 2008-10-05

2008-10-05T19:59:00.004+02:00

Treatment of patientes is ongoing for both of Diamyds trials. This is the latest status from Diamyd. Recruitment for the two phase III trials in Europe and USA is planned to be finished by April 2009. The NIDDK trial is planning to start recruiting in December 2008 and will begin including years 8-45, later dropping the age requirement to 3 yrs in preparation for the TrialNet prevention trial.

Information is constantly added to the official clinical trials page.

Timeline for GAD65 (Diamyd)

2008-08-27T19:03:00.003+02:00

Click on the image for a larger version.

GAD 65 Trial Information

2008-08-24T13:58:00.004+02:00

Click here for full screen.

Treatment with Diamyd is a clear benefit even after 30 months

2008-07-29T19:13:00.007+02:00

The image below shows the results 30 months after treatment.

The image shows the change in C-Peptide after a Mixed Meal Tolerance Test.

Top Left (A) : Given Diamyd 0-3 months after diagnosis.
Top Right (B) : Given Diamyd 3-6 months after diagnosis.
Bottom Left (C) : Given Diamyd 6-12 months after diagnosis.
Bottom Right (D) : Given Diamyd 12-18 months after diagnosis.

As you can see it's very important to treat early, while the patient still has living beta cells to preserve. The treatment seems to wear off after 15-20 months and this is why the Phase III trials will use additional booster injections of Diamyd at day 90 and 270. What we are looking for is a longlasting effect.

Could this cure a child who is newly diagnosed with Type 1 Diabetes? Yes. Are we sure it will work? No.

In my eyes we have a worst case of "only" prolonging the honeymoon period with 15-20 months. Best case is a sustained or increased amount of C-Peptide secretion even a few years after injection.

Im jumping ahead now, but if results are great on newly diagnosed children with 15% of their beta cells remaining. Imagine what would happen if we gave the vaccine to children with a high risk of developing Type 1 Diabetes or children with pre-diabetes. Both groups would have a higher amount of beta cells left to save. This is exactly what TrialNet are doing in their planned prevention trial. They will give Diamyd GAD65 vaccine to children who have a very high risk of developing Type 1 Diabetes. Remember that we are now very good at predicting who will get the decease years before outbreak.

If Diamyd GAD65 prevents the outbreak of Type 1 Diabetes in high risk children it can be administered proactively after a positive antibody screening.

Please note that the Phase III trial should be recruiting patients now in the US. Check back for clinicaltrials link as soon as it's published.

If you have LADA you want Diamyd

2008-07-26T22:31:00.003+02:00

At the European Association for the Study of Diabetes (EASD) Diamyd will have a poster presenting their 5 yr results on LADA patients.

The results are clear from the poster title; GAD65 vaccination significantly reduces insulin dependence at five years follow-up in a dose escalating study in adult-onset autoimmune diabetes patients

The results are very promising and together with the favourable phase II results on type 1 children, it's clear that Diamyd preserves beta cell function in diabetics.

The LADA results will be verified by a slightly larger phase III trial planned probably in 2009, while the type 1 diabetes phase III trials are currently ongoing.

Antibodies, What Does It Mean?

2008-07-05T18:38:00.007+02:00

This image from www.scielo.br shows the connection between the how many autoantibodies you have and the risk of developing Type 1 Diabetes.

If you are positive for two antibodies your risk of developing T1D within 10 years is 70%.

If you are positive for GAD65, which is one of the three/four major T1D antigens and diagnosed within 3 months you could be eligible for the Diamyd GAD65 Phase III trial.

Trial UPDATE

2008-07-01T13:06:00.003+02:00

USA:
Phase III (Diamyd) - 306 patients - Status: recruiting patients
Phase II (NIH/NIDDK) - 126 patients - Status: not started recruitment
TrialNet Prevention Trial - Status: no additional information

Europe:
Phase III (Diamyd) - 306 patients - Status: recruiting patients

Schedule:
For the Phase III trials recruitment is expected to be finalized in April 2009. Results will be available in fall 2010.

The NIH/NIDDK trial is expected to report in 2011.

Why Diamyd is not only for honeymooners

2008-06-30T21:10:00.002+02:00

Read this post by Joshua, I could not agree more.

We should see first patient treated in Diamyd, GAD 65 Phase III trial really soon.
According to the information released today, everything is on track. 612 patients to be treated by April 2009.

Recent studies find ways to shorten time to end-point for preventive trials

2008-06-15T00:29:00.007+02:00

According to the abstract "228-OR" presented at ADA 68th (2008), measuring post-challenge dysglycemia in trial members may be a good sign that they will later develop type 1 diabetes.

For trial members less than 13 years of age, 95% of those who had dysglycemia developed type 1 diabetes within 5 years. Mean for the whole group was 79%.

This is good news for all the preventive trials, since you may shorten the follow-up time with a few years.

Or to quote the abstract, "The high incidence of DG and the very high likelihood of T1D once DG occurs suggest that T1D prevention trials of individuals with normal glucose tolerance could potentially be shortened by including DG as an endpoint."

Abstract full name: "Incident Post-Challenge Dysglycemia as a Predictor of Type 1 Diabetes in the Diabetes Prevention Trial-Type 1 (DPT-1)"

TrialNet T1D Prevention Study with Diamyd!

2008-06-08T15:22:00.006+02:00

Update:
The TrialNet prevention study is now confirmed. The quote below is taken from diamyd.com

"Jay Skyler, chairman of TrialNet, presented their work and highlighted both the upcoming TrialNet phase II study with Diamyd(r) in recent onset type 1 diabetes, as well as NIH's/TrialNet's intention for a prevention trial with Diamyd(r) in subjects at high risk for developing type 1 diabetes."

Last year (at the ADA conference) it was mentioned that TrialNet with Jerry Palmer as Lead Investigator might start a Type 1 Diabetes prevention study, to investigate the possible benefits of giving Diamyd to high risk patients who have not yet been diagnosed.

The benefits if this work is very clear. It will answer a very important question: Since giving Diamyd early after diagnosis seems to help, what will happen if it's given even earlier? More beta cells left at the time of the first injection might greatly increase the effect of the Diamyd vaccine.

High risk persons to consider for this trial would be anyone who are a 1st or 2nd degree relatives to T1D patients.

To be included they would probably have to be between 3-45 years of age, have normal glucose tolerance and positive for GAD65 auto-antibodies.

The primary endpoint would be the breakout of T1D.

Credit: Most of the information from this post have been taken from the presentation Ake Lernmark did last year at ADA 2007.

More specific dates regarding Phase III trials (T1D)

2008-05-30T16:21:00.003+02:00

More specific dates from Diamyd today.

Start of Phase III in US and EU will happen within 0-2 months.
Results expected fall 2010, and then 9-12 months for market approval.

The NIH Phase II trial was planned because Diamyd is seen as one of the most promising ways towards a cure, according to the company.

Diamyd will attend the ADA conferance in San Francisco next week.

How Diamyd may cure older diabetes patients

2008-05-02T18:38:00.004+02:00

You have heard it a few times to many. Diamyd is only recruiting newly diagnosed patients. Does this mean that you who have had Type 1 Diabetes for 10 years is out of luck?

Not necessarily.

In the traditional view, insulin producing beta cells who got killed by the auto-immune reaction, was gone forever. That is why islet transplantation is a sought after research area. But what if the body can recreate the beta cells? That would mean that a 40 y/o patient with type 1 diabetes who got the Diamyd vaccine would be able to recreate 20% of the beta cells each year, meaning 100% recovery after only 5 years.

This is of course still very early and with a lot of "if".
- Diamyd vaccine must work (2 x phase III trials ongoing + 1 x phase II ongoing)
- The body must be able to recreate beta cells after destruction.

Even with only 20-30% of the beta cells, the patient would be much better of. Who wouldn't want a life-long honeymoon period?

I understand this is not proven science yet, but it's possible, with no big side effects and only 2-4 injections 4-8 weeks apart.

Some links:
http://www.healthcentral.com/diabetes/c/14/1390/beta-cell-explained
http://www.diabetesselfmanagement.com/articles/Diabetes_Definitions/Beta_Cell_Regeneration
http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-05-007.html
http://www.jci.org/115/1/5?content_type=abstract

NIDDK to hold the (NIH) Phase II trial

2008-05-02T16:01:00.005+02:00

Recent information on clinicaltrials.gov lets us know that it's NIDDK (The National Institute of Diabetes and Digestive and Kidney) who will conduct the Phase II trial.

126 patients will be enrolled.

42 patients: two injections of Diamyd 20ug vaccine 4 weeks apart, and the third 8 weeks after the second.
42 patients: two injections of Diamyd 20ug vaccine 4 weeks apart, and a placebo injections as the last one 8 weeks after the second.
42 patients: three injections of placebo as a control.

Primary endpoint is C-Peptide.

To be eligible for this trial you need to be between 8-45 years old, and diagnosed within the previous 3 months.

ClinicalTrials identifier for this trial: NCT00529399

Take care!

NIH will conduct a Diamyd Phase II trial

2008-04-19T11:18:00.003+02:00

Some new information about the American NIH (National Institute of Health) and a possible Phase II trial have been mentioned in a Swedish newspaper. The information is still very vague with no details released.

It will execute for two years and include 126 patients.

What will differ this trial from the one Diamyd has already made and when it will start is also unclear.

European Phase III trials approved

2008-03-21T09:36:00.006+01:00

Diamyd now also has approval from the Swedish Medical Products Agency to start Phase IIItrials. The trial will like its American parallel study include 306 newly diagnosed type 1 patients.

"Diabetes teams from approximately 20 Swedish pediatric clinics will meet in Linköping, Sweden, on April 4 to go through details for the study"

Diamyd is planning to get approval from additional 3-4 European countries, in order to add an additional ~20 clinics to the trial.

According to Diamyd the interest in the drug is strong, and parents of patients send inquires daily to Diamyd about inclusion in its trials. This will hopefully mean that patient recruitment will not take that long (6-9 months).

Good luck Diamyd, and all T1D patients!