PKD treatment pipeline

Since 1982, we have led the fight against PKD through the support of basic, translational and clinical scientists, vital research funding, and patient education. Today, we are encouraged by the significant strides we are making to find treatments. We have gone from a single drug in clinical trials five years ago to an approved drug, tolvaptan (brand name JYNARQUE™), 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. In 1982, when the PKD Foundation was established, little was known about the molecular genetics or mechanisms of the disease. The following list shows how much is now known, much of it due to the research funding by the Foundation. Each novel therapeutic addresses a unique pathway that is affected by the disease.

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 has 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. Results are expected in 2022.

Niacinamide

What it is

Niacinamide is a form of vitamin B3 available over the counter. It is 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, and therefore does not require approval by the FDA, although a pivotal trial would help to establish an optimal dosage regimen.

Clinical study status

Preliminary results from the ongoing uncontrolled, open label, pilot and feasibility study of niacinamide in polycystic kidney disease (NIAC-PKD1) show that niacinamide is safe and well tolerated in humans.

The Randomized, Controlled Pilot Study of Niacinamide in Polycystic Kidney Disease (NIAC-PKD2), which is being conducted at the University of Kansas Medical Center, is designed to determine the effects of niacinamide on markers of kidney injury, inflammation, and kidney function and cyst growth. Recruitment for this study is closed. Analysis is ongoing.

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

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, thus 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 active and ongoing but is no longer recruiting patients. Results are expected in 2020.

Tesevatinib

What it is 

Tesevatinib is a new drug compound that is a tyrosine kinase inhibitor designed to block key molecular drivers of tumor growth, metastases and drug resistance.

Why it may be a potential treatment for ADPKD 

Early clinical studies have shown that tesevatinib inhibits epidermal growth factor (EGFR), which promotes cyst growth in ADPKD.

Clinical study status 

A Phase 1 study has been completed, demonstrating that tesevatinib was generally well tolerated. Kadmon Corporation, LLC, is currently recruiting patients for a Phase 2 randomized, placebo-controlled study to compare and evaluate safety and efficacy of tesevatinib. This study is recruiting patients. Click here to learn more and find out if you are eligible to participate.

Tesevatinib is also the first drug to be tested in pediatric patients with ARPKD. Click here to learn more.

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 is 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 of children and young adults with ADPKD. The study is currently recruiting patients. Learn more about this clinical study.

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 is 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.

RGLS4326

What it is

RGLS4326 is a compound designed to inhibit microRNA-17, a key factor in the cell biology of PKD cyst cells.

Why it may be a potential treatment for PKD

Preclinical studies with RGLS4326 have demonstrated a reduction in kidney cyst formation, decreased cyst cell growth and preserved kidney function in animal models of ADPKD (not yet in humans). This type of drug is involved in the transcription or decoding of messenger RNA (mRNA) into proteins.

Clinical study status

In December 2017, Regulus Therapeutics Inc. announced that it had initiated he first-in-human Phase I study of RGLS4326 and completed dosing of the first cohort of healthy volunteers. Read the press release here.

Venglustat

What it is

Venglustat is a glucosylceramide synthase (GCS) inhibitor. Two glycosphingolipids –glucosylceramide (GL-1) and lactosylceramide are present in higher quantities in the kidneys from mouse models of PKD and from humans with PKD compared with normal kidneys. Glycosphingolipids play a pivotal role in cell membranes in both normal and PKD-affected kidney cells.

Why it may be a potential treatment for PKD

Because GL-1 is elevated in PKD kidneys, inhibition of the enzyme that makes GL-1 is thought to slow the growth of renal cysts. Initial studies in humans show venglustat to be well tolerated. It doesn’t affect serum creatinine, blood pressure or urinary output in normal volunteers.

Clinical study status

Sanofi Genzyme is currently recruiting for a phase 2/3 study of venglustat in patients with ADPKD between the ages of 18-50. Read here for more information.

Oxypurinol

What it is

Oxypurinol is the active metabolite of allopurinol, a drug used commonly for the treatment of gout.

Why it may be a potential treatment for PKD

Patients with chronic kidney disease, including PKD are often at risk of hyperuricemia (too much uric acid in the blood), which is thought to be a risk factor for the progression of renal and cardiovascular disease, as well as the cause of gout. Oxypurinol has been shown to reduce the level of circulating uric acid. It is hypothesized to have a better benefit/risk profile than allopurinol.

Clinical study status

Xortyx, the company developing a proprietary formulation of oxypurinol is planning a phase 2/3 clinical trial to begin in 2019.

Lixivaptan

What it is

Lixivaptan is a member of the same drug class as tolvaptan. However, it may distinguish itself from tolvaptan by having a distinct safety profile even though its mechanism of action is the same: blockade of the renal vasopressin receptor.

Why it may be a potential treatment for PKD

Like tolvaptan, lixivaptan is predicted to slow the progression of PKD. However, because it has a different chemical structure than tolvaptan, lixivaptan may not be associated with adverse liver effects. Whether this is true will be established in clinical trials.

Clinical study status

Palladio Biosciences, the company developing lixivaptan, is currently recruiting for a phase 2 clinical trial. See here for more information.

Bardoxolone methyl

What it is

Bardoxolone methyl is a novel drug candidate being developed for chronic kidney diseases by Reata Pharmaceuticals.

Why it may be a potential treatment for PKD

Bardoxolone methyl has shown efficacy in the treatment of various chronic kidney diseases. Phase 2 results indicate that it may also prevent the decline in renal function in patients with ADPKD.

Clinical study status

Reata Pharmaceuticals is preparing to begin a phase 2/3 study of bardoxolone methyl in ADPKD patients. As with all clinical trials, the protocol, which defines patient qualifications, dose regimen, and duration, the final protocol is under active development. This study could start soon.