Research pipeline

Since 1982, we’ve led the fight against PKD through the support of basic, translational, and clinical scientists; vital research funding; and patient education. Today, we’re encouraged by the significant strides we’re making to find treatments. We’ve gone from a single drug in clinical trials five years ago to an approved drug, tolvaptan, and more drugs in the pipeline today than ever before.

Read on to learn more about the treatments for PKD currently being developed in the United States.

Learn more about clinical trials and the difference between Phases 1–3. 

Patients play a key role in the research and development process by volunteering to participate in clinical studies. From observational studies to clinical trials, you can help researchers unlock the secrets of PKD and find a treatment by participating in a study. Learn more.

Tolvaptan

On April 24, 2018, the U.S. Food and Drug Administration (FDA) granted approval of tolvaptan to be the first treatment in the United States for adult patients with autosomal dominant polycystic kidney disease (ADPKD), the most common form of polycystic kidney disease (PKD).

Tolvaptan is a medication (taken twice a day as an oral pill) that affects how the kidneys control the concentration of urine. It’s been shown to slow down the growth of kidney cysts (total kidney volume) when it is taken for a long time (several years) by adults at risk of rapidly progressing ADPKD. This may help protect the function of your kidneys and delay the need for a kidney transplant or dialysis. Though your kidney function would continue to decline, it would be at a slower rate. Learn more here.

Bardoxolone methyl

What it is

Bardoxolone methyl is a novel drug candidate that belongs to a class of drugs called nuclear erythroid 2-related factor (Nrf2) activators.  Nrf2 activation has been shown to improve the function of mitochondria and have anti-inflammatory effects as well. Bardoxolone is being developed by Reata Pharmaceuticals for several rare, genetic chronic kidney diseases, including Alport Syndrome and ADPKD.

Why it may be a potential treatment for PKD

Bardoxolone methyl has shown an improvement in kidney function compared to placebo in a Phase 3 study in Alport Syndrome. The application for approval to treat Alport Syndrome was filed by Reata in April 2021, and the FDA is expected to act on this application by February 2022. Phase 2 results indicate that it may also prevent the decline in kidney function in patients with ADPKD.

Clinical study status

Reata Pharmaceuticals is currently studying bardoxolone for the treatment of ADPKD in the Phase 3 FALCON study.  This is a 2-year study evaluating the safety and efficacy of bardoxolone in approximately 550 patients world-wide. Initial results on the outcomes of the first year of treatment should be available within 15 months of completion of study enrollment. We rely on ADPKD patients to sign up for the study to move this research forward. Learn more about what participating in the FALCON study looks like here.

Lixivaptan

What it is

Lixivaptan is a member of the same drug class as tolvaptan, and inhibits the function of the vasopressin 2 receptor.. Lixivaptan is being developed by Palladio Biosciences for ADPKD.

Why it may be a potential treatment for PKD

Like tolvaptan, lixivaptan is predicted to slow the progression of ADPKD. However, because it has a different chemical structure than tolvaptan, lixivaptan is thought to not be associated with adverse liver effects as seen in some patients receiving tolvaptan therapy. We’ll know whether this is true through clinical trials.

Clinical study status

Palladio Biosciencesis is currently studying lixivaptan for the treatment of ADPKD in a Phase 3 study called The ALERT Study.  This is a 1-year study evaluating the liver safety, non-liver safety, and efficacy of lixivaptan in up to 50 patients who have permanently discontinued tolvaptan due to liver chemistry test abnormalities while on that drug. Learn more about what participating in The ALERT Study looks like here.

Tolvaptan in ARPKD

What it is

Tolvaptan was approved by the FDA to treat ADPKD in 2018. It is a medication (taken twice a day as an oral pill) that affects how the kidneys control the concentration of urine. It’s been shown to slow down the growth of kidney cysts (total kidney volume) when it is taken for a long time (several years) by adults at risk of rapidly progressing ADPKD. It is now being studied in pediatric ARPKD patients.

Why it may be a potential treatment for PKD

Tolvaptan is an approved drug that inhibits the vasopressin pathway by blocking the activity of the vasopressin receptor 2 (V2).  Preclinical studies of tolvaptan in rat models of PKD in which the causative gene of ARPKD, PKHD1, is mutated, demonstrated a reduction in kidney cyst formation, decreased cyst cell growth, and preserved kidney function, suggesting the vasopressin pathway may also play a role in the progression of the renal manifestations of ARPKD.  The potential role of the vasopressin pathway in promoting cyst formation caused by mutations in PKHD1 has also been confirmed by genetic studies in rat.

Clinical study status

Otsuka is currently studying tolvaptan in a two phase 3 studies in ARPKD. These are an 18 month and a 2-year study, each evaluating the safety and efficacy of tolvaptan in up to 20 patients under the age of 18. Read more to learn about what participating looks like.

Tesevatinib in ADPKD

What it is 

Tesevatinib is a novel drug candidate that belongs to a class of drugs called receptor tyrosine kinase inhibitors. Receptor tyrosine kinases play an important role in promoting cell growth in the body. However, when tyrosine receptor kinases are mutated, or their activity isn’t properly controlled in the body, they can promote uncontrolled cell growth, and are implicated in the formation and metastasis of some tumors.   Tesevatinib is being developed by Kadmon Corporation for ADPKD, as well as other indications in which EGFR inhibition may impact disease progression.

Why it may be a potential treatment for ADPKD 

Because cyst formation and growth represent a form of uncontrolled cell growth, it’s thought that tyrosine receptor kinase inhibitors may reduce cyst formation and growth in ADPKD. Additionally, one of the receptor tyrosine kinases inhibited by tesevatinib, the epidermal growth factor receptor (EGFR) is part of signaling pathways that are known to promote cyst growth in ADPDK. Phase 1 studies of tesevatinib in ADPKD demonstrated that tesevatinib was generally well tolerated.

Clinical study status 

Kadmon  is currently studying tesevatinib in a phase 2 study in ADPKD. This is a 2-year study evaluating the safety and efficacy of tesevatinib in approximately 80 patients in the U.S. The study is no longer recruiting, and preliminary findings from the study are anticipated to be available in early 2022.

GLPG2737

What it is 

GLPG2737 is a novel drug candidate that belongs to the class of drugs called cystic fibrosis transmembrane conductance regulator (CFTR) inhibitors. CFTR is a chloride channel, meaning it specifically transports chloride across cellular membranes. GLPG2737 is being developed by Galápagos for the treatment of ADPKD.

Why it may be a potential treatment for ADPKD 

CFTR promotes cyst growth by secreting chloride ions into the lumen (interior) of cysts. Inhibition of CFTR has been shown to reduce cyst growth in cellular models of ADPKD, as well as in animal models of ADPKD.  Phase 1 single and multiple dose studies of GLPG2737 have been completed in healthy volunteers and demonstrated that the drug was generally well tolerated.

Clinical study status 

Galápagos is currently studying GLPG2737 for the treatment of ADPDK in the phase 2 MANGROVE Study.  This is a one-year study evaluating the safety and efficacy of GLPG2737 in up to 60 patients at risk of rapidly progressing disease.  This trial is being conducted in seven countries in Europe. There are currently no studies on GLPG2737 in the United States.

RGLS4326

What it is

RGLS4326 is a novel drug candidate that belongs to a class of drugs that target microRNAs. Micro RNAs are a collection of RNA molecules in cells that play multiple roles in the regulation of cell function. RGLS4326 is being developed by Regulus Therapeutics for ADPKD.

Why it may be a potential treatment for PKD

The specific microRNA targeted by RGLS4326, miR-17, is involved in regulating the production of PKD1 and PKD2 proteins, the proteins encoded by the causative genes in ADPKD. Preclinical studies with RGLS4326 have demonstrated direct regulation (an increase in the amounts produced) of PKD1 and PKD2 in human ADPKD cyst cells, as well as a reduction in kidney cyst formation, decreased cyst cell growth, and preserved kidney function in animal models of ADPKD. A phase 1 multiple dose study of RGLS4326 was completed in healthy volunteers, and demonstrated that the drug was generally well tolerated.

Clinical study status

Regulus is currently studying RGLS4326 for the treatment of ADPKD in a phase 1 dose ranging study. This is a 12-week open label study evaluating the relationship between the RGLS4326 dose and ADPKD biomarkers in approximately 27 patients in the U.S.. We rely on ADPKD patients to sign up for the study to move this research forward. Learn more about what participating in the RGLS4326 study looks like here.

Tesevatinib in ARPKD

What it is 

Tesevatinib is a novel drug candidate that belongs to a class of drugs called receptor tyrosine kinase inhibitors. Receptor tyrosine kinases play an important role in promoting cell growth in the body. But, when tyrosine receptor kinases are mutated, or their activity isn’t properly controlled in the body, they can promote uncontrolled cell growth, and are implicated in the formation and metastasis of some tumors. Tesevatinib is being developed by Kadmon Corporation for ARPKD.

Why it may be a potential treatment for ARPKD 

Because cyst formation and growth represent a form of uncontrolled cell growth, it’s thought that tyrosine receptor kinase inhibitors may reduce cyst formation and growth in ARPKD. Additionally, one of the receptor tyrosine kinases inhibited by tesevatinib, the epidermal growth factor receptor (EGFR), is part of signaling pathways that are known to promote cyst growth in ARPKD. Phase 1 studies of tesevatinib in ADPKD demonstrated that tesevatinib was generally well tolerated.

Clinical study status 

Kadmon is currently studying tesevatinib in a phase 1 study in ARPKD. This is a pediatric study evaluating the safety and efficacy of liquid tesevatinib in approximately 10 patients in the U.S. The study is no longer recruiting, and preliminary findings from the study should be available soon.

Venglustat

What it is

Venglustat is a novel drug candidate that belongs to a class of drugs called glucosylceramide synthase (GCS) inhibitors. GCS’s produce glycosphingolipids, which play a pivotal role in cell membranes in both normal and PKD-affected kidney. Venglustat was being investigated by Sanofi Genzyme for ADPKD, as well as other indications in which glycosphingolipid production is thought to impact disease progression.

Why it may be a potential treatment for PKD

Two specific glycosphingolipids are present in higher quantities in the kidneys from mouse models of ADPKD and from the kidneys of people with ADPKD. Compared to those without, this suggests their elevation may play a role in disease progression. Based on this observation, inhibition of the specific GCS that produce these compounds are thought to slow the growth of cysts in patients with ADPKD. Studies in animal models have shown that GCS inhibition reduces cyst formation and growth, and initial studies in humans show venglustat to be well tolerated.

Clinical study status

Sanofi Genzyme evaluated venglustat for the treatment of ADPKD in the Phase 2/3 STAGED-PKD study.  In June 2021, Sanofi Genzyme announced that it is halting this clinical trial due to a failure to meet futility criteria. This means that the data from the first year of the trial did not demonstrate a change in the rate of total kidney volume growth in patients taking the study drug versus placebo, and likely doesn’t offer a significant preventative effect against kidney cyst growth in ADPKD.

 

 Drug Repurposing

Curcumin

What it is

Curcumin is a dietary supplement that is produced by some plants and is found in the spice turmeric.

Why it may be a potential treatment for PKD

Curcumin activates transcription of key antioxidants, suppresses inflammation, and reduces cell proliferation (growth). Because of these properties, it’s thought that it could have positive effect in reducing cell growth as well as improve the health and function of arteries in ADPKD.

Clinical study status

The University of Colorado Anschutz Medical Campus is conducting a study to determine if curcumin can improve the function of blood vessels in children and young adults with ADPKD. The study is no longer recruiting patients, and findings from the study should be available soon.

Metformin

What it is

Metformin is a first-line, FDA-approved drug to treat type 2 diabetes.

Why it may be a potential treatment for ADPKD

Mouse models have shown that metformin blocks the aerobic glycolysis pathway, which is linked to cell proliferation that causes cysts to form and grow. When treated with metformin, mice with PKD show inhibition of cyst growth. Metformin has a long established safety profile because it’s been used for decades in the treatment of type 2 diabetes.

Watch our recorded webinar, PKD therapies and potential candidates, to learn more.

Clinical study status

Researchers at Tufts University in Boston and at the University of Maryland in Baltimore are currently conducting this trial; recruitment has closed. Preliminary results show that metformin is tolerabile and safe in ADPKD patients. A larger study will be needed to determine the effectivess of metformin to slow disease progression.

Niacinamide

What it is

Niacinamide is a form of vitamin B3 available over the counter. It’s used for treating diabetes and certain skin conditions.

Why it may be a potential treatment for ADPKD

Niacinamide has been shown to inhibit a regulatory protein called sirtuin 1, which promotes cell growth and may promote cyst growth in PKD. Inhibition of sirtuin 1 may slow or stop cyst growth.

Niacinamide could be an appealing treatment option for PKD because of its low cost and favorable safety profile. The European Nicotinamide Diabetes Intervention Trial (ENDIT) study showed that large doses of niacinamide are safe in humans. Additionally, niacinamide is a dietary supplement, so it doesn’t require approval by the FDA. Studies aimed to establish an optimal dosage for ADPKD patients.

Clinical study status

The Randomized, Controlled Pilot Study of Niacinamide in Polycystic Kidney Disease (NIAC-PKD2), conducted at the University of Kansas Medical Center, was designed to determine the effects of niacinamide on markers of kidney injury, inflammation, kidney function, and cyst growth. Unfortunately, although the drug was well-tolerated in ADPKD patients, the researchers observed no benefit compared to those on placebo. 

Pioglitazone

What it is

Pioglitazone is an FDA-approved treatment for type 2 diabetes.

Why it may be a potential treatment for ADPKD

Pioglitazone has been shown to inhibit chloride secretion into cysts, which is a key factor in cyst growth. When chloride moves into the cyst, water follows, filling the cysts with fluid and causing them to grow. By inhibiting chloride from moving into cysts, pioglitazone may potentially slow or stop cyst growth. Pioglitazone may also inhibit cyst cell division by causing terminal cell differentiation.

Watch our recorded webinar, A discussion about pioglitazone Actos as a potential therapy for PKD, to learn more.

Clinical study status

Researchers at Indiana University Purdue University in Indianapolis (IUPUI) are conducting a pilot clinical trial to test the safety and efficacy of low doses of pioglitazone on ADPKD progression. This study is ongoing but is no longer recruiting patients. Results are expected in 2021.

Statin therapy

What it is

Statins comprise a class of drug that lowers the level of cholesterol in the blood.

Why it may be a potential treatment for PKD

In addition to their efficacy in lowering cholesterol, statins also have anti-proliferative, anti-inflammatory, and antioxidant effects. Due to this and their relative safety, it’s thought they could potentially be used to slow the progression of ADPKD.

Clinical study status

The University of Colorado Anschutz Medical Campus is conducting a study to learn if pravastatin (a common statin) is helpful in slowing down the progression of ADPKD. This study is actively recruiting patients. Learn more about the study and see if you are eligible here.

 

Last updated June 2021.