Exciting new drug slows or even halts kidney failure

Earlier this month the biotech company Dimerix Pty Ltd, based in Melbourne, reported extremely encouraging results from its recent clinical trial for chronic kidney disease, with their anti-inflammation drug DMX-200.

 

Kathy Harrison CEO

Kathy Harrison, CEO of Demerix 

Recently, I was delighted to meet with the CEO of Demerix, Ms Kathy Harrison and to talk about the results and the opportunities for kidney patients.

 

What DMX-200 does

One of the first signs of kidney disease is albumen in our urine.  Albumin is a type of protein that is normally found in the blood. We all need protein; it’s an important nutrient that helps build muscle, repair tissue, and fight infection.  But protein should be in our blood, not our urine.

If our kidneys are damaged (by high blood pressure, diabetes, etc), protein can “leak” out of the kidneys into our urine. Having protein in urine is called “albuminuria” or “proteinuria.” If that is not bad enough, our immune system often then reacts by inappropriately attacking our own kidney cells causing inflammation and even more proteinuria, in a rapid downhill spiral.

Dimerix’s DMX-200 is designed to help slow or even stop proteinuria, by reducing the inflammation.

Results

New drugs usually go through three phases before release

  • Phase I clinical trials test a small group of people (e.g. 20-80) to evaluate safety (e.g. to determine a safe dosage range and identify side effects).
  • Phase II clinical trials may test from twenty to several hundred to check that it works as intended and to further evaluate its safety
  • Phase III studies may test several hundred to several thousand by comparing the therapy to other therapies, monitoring for adverse effects, determining dosing schedules etc.

These results were from the first part of a Phase II trial (Phase IIa), conducted in Melbourne. Of the 24 patients who completed the trial, six achieved more than a 50% drop in proteinurea levels (25%). Fifty percent is a major reduction and a clinically meaningful result, halting what can be a rapid decline to complete kidney failure.

Conversely, four weeks after treatment stopped, three patients experienced more than a 50% increase in proteinurea levels, returning to previous, pre-trial levels. This suggests that the Dimerix treatment not only slowed the proteinurea but helped maintain it at that lower level.

Importantly, the trial also demonstrated that the treatment appears to be very safe: there were no serious adverse events.

Aside from the promising results, Ms Harrison said further analysis also identified which patient sub-groups are more responsive to this treatment, but at this stage that data is being kept confidential for competitive reasons.

Special early access

Of the 24 patients, 11 (45%) have continued on treatment under the Special Access Scheme. This is an arrangement where the TGA (Australia’s FDA) allows Dimerix to offer patients the opportunity to stay on the treatment after finishing the trial (at little or no cost!), even though it has not been formally approved.

The Next Trial – Getting involved

The next trial, the Phase IIb study, is expected to start towards the end of 2017. It will look at a more specific dose and treatment for a longer period at that optimum dose. It’s expected that about 30 patients will be treated for 6 months.

This new study will recruit a more targeted patient population based on responders in the Phase IIa trial, in addition to patients with the rare FSGS (focal segmental glomerulosclerosis) disease, which is one of the causes of chronic kidney disease.

The new study will be conducted around Australia, in Melbourne, Sydney, probably Brisbane and Perth.

If you wish to be involved, you can register your interest now via info@dimerix.com, or shortly, via a Registration button on the website. Dimerix will acknowledge your interest and add your name to their register of interested patients. In the last quarter of 2017, they will advise you of the process for getting involved (via your nephrologist).

DMX-200 is an exciting new development for patients with chronic kidney failure everywhere. Unlike stem cell treatments, promising, but on the distant horizon, this has the potential, to slow and even stop proteinurea in its tracks for some patients, now. It’s so close we can almost touch it – in fact, you can if you are part of the trial.

General release could be a year or more away, but from these results, DMX-200 is shaping up to be our next weapon of choice in humanity’s ongoing war against kidney disease.

Dimerix LogoNote: For the speculators amongst us, Dimerix shares are available on the Australian Stock Exchange as DXB, at $0.012 per share.

 

For the technically minded

Dimerix’s treatment involves the combination of two existing drugs, irbesartan with propagermanium. Using its core technology, called Receptor-HIT, Dimerix hypothesised that two receptors that are commonly found in the kidney, angiotensin II type I and CCR2, have a joint interaction. In preclinical studies, it then showed that by blocking both receptors, more than an additive effect could be achieved in kidney disease. Irbesartan, an anti-hypertensive drug that is prescribed to 70% of people with CKD, blocks the angiotensin receptor and propagermanium, which is an anti-inflammatory compound, blocks the CCR2 receptor.

All patients in the study were dose escalated across five different doses from 30 mg per day to 240 mg per day of propagermanium (no placebos). All patients entering the study were already receiving irbesartan. One aspect the company is building data on is the optimum dose with animal studies and results from competitors showing that too high a dose can reduce treatment benefit.

 

 

Life 2.0 – a chance to fix the faulty bits?

dna-crane

Rebuilding DNA with CRISPR. Source: New Yorker, Illustration by Todd St.John

BIG things are happening in genetics, for BigD-ers and for the rest of the world. Scientists have discovered a naturally-occurring, highly accurate gene editor, that can be used to cut and paste or delete genes or parts of genes in DNA. They can use the editor to remove a disease-causing mutation, replace faulty or undesirable parts of a gene or to turn a gene off completely.

What could this mean? Say you’ve inherited a genetic mutation that guarantees you’ll get polycystic kidney disease by the time you reach adulthood. And that it is most likely you will spend the rest of your life on dialysis.

What if the mutant genes that cause polycystic disease, passed down from generation to generation, can be clipped out of your genome entirely and you never pass it on to any of your offspring? (more…)

Kidney disease: meant-to-be or dumb luck? Part 2 – DNA

DNAOne of the (many) cool and wondrous benefits of being alive in the 21st Century is our ability to look deeply into our own bodies, right down to the very building blocks of life, our DNA, to glimpse our personal program for life.  Another almost-as-amazing benefit is that it costs just $99!

I was keen to check it out to see if my DNA had my kidney failure pre-programmed or if it was just dumb bad luck.

Getting started

I had read quite a bit about 23andMe and had long been keen to see what it had to offer.  So I clicked buy and began my journey. (more…)

Kidney disease: meant-to-be or dumb luck? Part 1 – Chance

gladstone ganderI have often wondered if my kidneys were programmed to fail when I was born, or if they were simply the victim of a rough and tumble world; or maybe a bit of both.

I know, everybody is different, but maybe my case could be useful for others.

I had some kind of blockage that stopped urine from leaving my left kidney, which eventually destroyed it.  It happened when I was 19, full of beans, and in the Navy.  (more…)

MSCs help us Reject Rejection

mesenchymal_stem_cell 2The light of rejection-free, healthy kidney transplants has entered the tunnel, and should arrive at our end in just three to five years.

Last month a senior researcher from the Cell and Tissue Therapies WA at the Royal Perth Hospital (CTTWA) presented a paper to the Renal Society of Australia‘s annual conference that has profound implications for us BigDers.  It detailed their early clinical trial successes in using Mesenchymal Stem Cells (MSCs) to stop kidney transplant rejection and to repair acute kidney injury (among many other medical wonders). (more…)

Every donor kidney a perfect match: no more transplant drugs!

Stem CellsWe all hate rejection.  It hurts us somewhere deep inside.  And those of us who’ve had an organ transplant hate it most of all.  Because the only way to make all that pain go away is by taking a hearty (sometimes heroic) dose of anti-rejection drugs.

Rejection is driven by our body’s immune system, a collection of cells (T cells) that recognise and destroy foreign cells: germs, poisons, other bits that find their way into us. All cells have proteins called antigens on their surface.  As soon as these antigens enter our body, the immune system recognises that they are not from our body and attacks them.

When we receive an organ transplant, our immune system (more…)

Dialysis news flash!

It’s been an interesting news week for BigD-ers, with a major advance in stem cell technology  It wont happen tomorrow, but the potential is now the possible: growing a new kidney from stem cells.   It’s not certain yet whether it will be done inside the body, or in a dish and transplanted when full grown, but if we can hang around a few years…

Just click on the headlines below for more.

Australian scientists grow mini-kidney in lab 

Stem cell mini-kidney in a dish

Plus:

University of Queensland kidney breakthrough a step forward in bio engineering

Dialysis needling: if at first…

 

Buttonholes

Buttonholes!

Josie (not her real name) emailed me recently about a problem she had getting one of her needles in:

 

Hi Greg

I hope you don’t mind me getting in touch. My name is Josie, I live in the UK and started home haemo a few months ago. I have had a problem with my fistula tonight and because it is Friday night here I can’t get hold of any of the nurses from my training unit, and having followed your blog I thought I could seek your advice… as I say, I hope you don’t mind me doing so. (more…)

Dialysis and Fluid Restrictions – Tips and Tricks

This week, a guest post from Ros Ball, Past President and currently Secretary of DATA, the Dialysis and Transplant Association of Victoria (Australia).  You may remember Ros when I wrote about her in June a couple of years ago.  She and her husband Charlie have outfitted their caravan with a dialysis machine and travel where most BigD-ers fear to tread:  the wide open spaces of the outback.  Ros’s get up and go, regardless of the demands of BigD is an inspiration, and puts the rest of us sometime travellers in the shade. (more…)

Dialysis: Back to the future with implantable artificial kidney

Hello and welcome to my first post for the New Year.  I hope you had a good Christmas and celebrated the arrival of 2011 in a style that set the tone for the year ahead.  My New Year was easy-going: we went to see The King’s Speech at the movies on New Year’s Eve, followed by a drive to Falls Creek, Victoria’s biggest alpine resort on New Year’s Day.  We stayed overnight and I was back in time for the BigD the next day.

The King’s Speech was a great movie: fabulous acting by Colin Firth and Geoffrey Rush and an inspiring message about how persistence and courage can win you back your life (a familiar theme, and not just for stammerers). (more…)