Farabursen - What is it and How Does it Impact PKD Progression?

farabursen medication research Sep 12, 2025

Farabursen, previously known as the experimental medication RGLS8429, is generating a lot of excitement in the PKD community – and it isn’t even available yet!

Polycystic kidney disease (PKD) starts at the genetic level. Every person on earth has two copies of the PKD1 and PKD2 genes. ADPKD happens when there’s a change, a mutation, in one of these genes. This mutation alters the PKD gene instructions for making kidney-specific protein molecules that are essential for your kidneys structure and function. When these proteins are not made correctly, cysts begin to form and grow, disrupting normal kidney tissue over time.

Now, when I say “protein,” I don’t mean the kind on your plate – I am referring to small molecules, made up of amino acids, your body uses to carry out vital functions.

To understand Farabursen, and how it could potentially slow PKD progression, we need to start at the very beginning: your genes.

But first, let's do a quick refresher on DNA and genes. Stick with me – this will make it much easier to understand why this experimental medication is showing so much promise.

Farabursen is moving into the final phase of testing, human clinical trials – a critical step before it could become available to help combat Polycystic Kidney Disease.

DNA and Genes: What You Need to Know

DNA: Your Complete Instruction Manual

DNA, which stands for deoxyribonucleic acid, is a long double helix molecule that carries all of your unique genetic information. Think of DNA as your body's complete instruction manual.

Genes: The Instruction Pages

A gene is a very specific section of DNA that provides your cells with detailed instructions for making individual body proteins. Those proteins each carry out particular functions in your body, like building tissues, transporting oxygen, fighting infections, or sending signals between cells. Think of your genes, of which humans have upwards of 21,000, as each containing a different set of instructions housed in your DNA Instruction Manual. Your body copies the instructions from each gene and actively uses them.

RNA: The Messengers

Another important molecule to know about is RNA, which stands for ribonucleic acid. There are different types of RNA; I am just going to touch on the types of RNA that are important to understand why Farabursen is being clinically tested as a treatment for Polycystic Kidney Disease.

Stick with me as I get a little science geeky, in a simplified way. The first type of RNA is messenger RNA (mRNA). Messenger RNA carries the copied instructions from your genes to where they can be used to make proteins, to a ribosome. Messenger RNA is exactly what it sounds like: a messenger that carries instructions to where they need to be.

Ribosomes: Protein Factories

Ribosomes are the “factories” where new proteins are made. The ribosome reads the copied gene instructions, provided by the messenger RNA, and follows them to make a new protein. That protein is a molecule made up of a chain of amino acids - much like a string of beads.

Both the PKD1 and PKD2 genes carry instructions for making proteins, which are called polycystin proteins. When either of the PKD1 or PKD2 genes is mutated, things can start to go awry in the kidney. (More on that in a moment!)

When needed, there is a way to stop this protein-making process, an “off switch”. This "off switch" helps regulate how much new protein is made from a specific gene’s instructions - helping to keep everything in check and to ensure your body and kidneys function smoothly.

MicroRNA: The Off Switch

This is where another type of RNA comes in —microRNA, or miRNA for short. These tiny molecules are a gene's “off switch.” They bind to the messenger RNA and block them from sharing the copied gene instructions with the protein-making factories, the ribosomes. In short, microRNAs stop genes from making too much of one type of protein.

Putting It Together: DNA in Action

DNA is your body's master instruction manual. Within that manual, your genes are the individual instructions. To use those instructions, messenger RNA carries a copy of them to ribosomes —the protein-making factories, where new proteins are made. MicroRNAs are the “off switch” for this process. They ensure your cells don’t make too much of any one protein.

The experimental medication Farabursen targets a PKD-specific microRNA, that "off switch", with the goal of making more polycystin protein to help potentially slow, and or stop, cyst growth and PKD progression.

DNA is the complete instruction manual that contains all your genetic information.
Genes are the individual instructions within specific sections DNA.
Messenger RNA (mRNA) carries a copy of a gene's instructions to the ribosomes.
Ribosomes are the factories where the copied instructions are used to make essential body proteins.
MicroRNA (miRNA) is the "off switch" that stops the protein making process.

Polycystic Kidney Disease

Now that we’ve had a quick refresher on genes and DNA, let’s focus on the PKD genes themselves. This will help highlight how Farabursen is proposed to work.

PKD, Genes and Proteins

Every human has two copies of the PKD1 and PKD2 genes—one set from each parent. Those genes carry the instructions to make proteins, called polycystin proteins, which are important for kidney tubule structure and maintaining kidney health.

ADPKD is caused by mutations of the PKD1 or PKD2 genes, with an estimated 85% of PKD being caused by PKD1 mutations. When PKD genes are mutated, their instructions get scrambled. This leads to cells that don’t work as they should—setting the stage for the cyst growth seen in autosomal dominant polycystic kidney disease (ADPKD).

PKD is complicated (you can say that twice and mean it!), but in general, the PKD gene mutations cause changes in kidney tubule structures, create altered growth pathways, and ultimately lead to cyst formation, multiplication, and unwanted growth.

PKD and MicroRNA

With Polycystic Kidney Disease, microRNA is upregulated, meaning there is a lot more of it than normal. The specific miRNA involved with Polycystic Kidney Disease is microRNA-17.

With PKD, there is more microRNA, a lot more, putting the brakes on, or altogether stopping, the production of those polycystin proteins. In general, PKD’ers make only 10-15% of what is considered a normal level of polycystin protein. PKD is a “polycystin protein problem”!

Farabursen: The On Switch

Farabursen is what is called an oligonucleotide medication; it targets and blocks that specific microRNA that is elevated with PKD, microRNA-17. Remember, microRNAs are the “off switch” for making your body’s proteins. The high levels of microRNA-17, with polycystic kidney disease, mean that much less polycystin protein is made. Your kidneys need polycystin protein to be healthy and function properly.

Consider Farabursen to be the “on switch”. By blocking the microRNA-17, Farabursen essentially flips the on switch for the messenger RNA to share its instructions for making polycystin protein. More polycystin protein helps your kidneys function better, and you have more “normal” levels of essential kidney proteins. With more polycystin available, kidney cells function better, and the hope is that cyst growth can be slowed—or even stopped.

In short, Farabursen targets microRNA-17, the “off switch” that prevents polycystin proteins, which are essential for healthy kidneys and function, from being made. By blocking the microRNA-17, Farabursen is essentially the “on switch” that kickstarts the PKD1 gene to make more polycystin proteins. The belief, and what studies have shown so far, is that restoring levels of the polycystin protein helps slow PKD progression.

Study Results: What We’ve Learned So Far

Farabursen has completed a Phase 1 clinical trials with positive results. These studies showed that the drug was safe and well-tolerated, and it appeared to slow the growth of kidneys in people with ADPKD.

In the trials, patients taking Farabursen had almost no increase in their kidney size, while those on a placebo saw their kidneys grow at a typical rate. The drug also increased levels of polycystin-1, the important protein that people with PKD usually don’t make enough of. This suggests that Farabursen is doing what it’s supposed to do: helping the kidneys function more normally.

What’s Next for Farabursen?

The company developing Farabursen, Novartis, has plans to begin Phase 3 trials later this year. Recruitment for the upcoming studies hasn't begun as of the date of this blog’s publication.

The upcoming clinical trial, which has been reported have a 12-month intervention period, will be followed with great anticipation and interest. The results that will be studied are total kidney volume (TKV) after the 12-month intervention period, where participants receive Farabursen or a placebo. In addition, kidney function (eGFR) will also be looked at after 24 months.

Who qualifies for the upcoming study?

According to a January 2025 presentation by Regulus, the company originally behind Farabursen, criteria to considered for participation in the upcoming clinical trial include:

18-70 years old
Mayo Classification is 1C, 1D, or 1E
Kidney function, eGFR, of 25-90
If you are 18-30 years old, and your Mayo Classification is 1E, an eGFR up to 140
Not taking Tolvaptan or Jynarque (can do a 3-month washout period)

What can you do?

If you are interested in being considered for the upcoming Phase 3 Trial for Farabursen, talk to your nephrologist. Ask if if you PKD center is participating in the upcoming clinical trial. If you know someone who would benefit from learning more about Farabusen, send them this blog!

Your advocate,

Diana, The PKD Dietitian

Please Note

Information provided in this blog was up to date at the time of publication. I reached out to Novartis, but they were unable to provide additional, or updated details on the upcoming clinical trial.