ADPKD News Summary

Eloxx Pharmaceuticals announced the finalized design of its global EXPRESS Phase 2 trial: approximately 60 adults with genetically confirmed PKD1/PKD2 nonsense mutations will be randomized 1:1 to exaluren or placebo for 52 weeks, with annualized height-adjusted total kidney volume (htTKV) growth as the primary endpoint.

Exaluren is a "read-through" agent designed to let ribosomes bypass premature stop codons and restore full-length polycystin-1. A substantial durable htTKV effect could support Breakthrough Therapy designation; the FDA lists htTKV as a potential surrogate endpoint for accelerated approval in ADPKD. First dosing is expected in Q3 2027 with topline data in 1H 2029. Orphan drug status has been granted in the US and EU. This is an early-stage program targeting a specific genetic subtype — far from clinical availability.

Source: Eloxx Pharmaceuticals press release (2026-10-20) · Read more

npj Digital Medicine published MEDA-PKD, a near-real-time analytics platform integrating routine clinical and research data from the German AD(H)PKD Tolvaptan Registry (NCT02497521). As of March 2026 it visualized data from 1,735 patients with a mean follow-up of 796 days.

Platform analysis showed tolvaptan treatment improved the annual eGFR decline rate by approximately 27% under real-world conditions (p=0.00015), with a greater response in men than women. The results provide real-world corroboration of tolvaptan's effectiveness in routine practice and demonstrate the potential of disease-specific registry platforms for individualized decision-making.

Source: npj Digital Medicine (2026-10-20) · Read more

The American Journal of Nephrology published the protocol of a single-site RCT randomizing 120 adults with ADPKD and overweight/obesity to a 24-month daily caloric restriction (DCR) behavioral weight-loss intervention or control, assessing whether weight loss slows kidney growth. Murine studies showed mild-to-moderate food restriction significantly slows cyst growth, and human pilot data support the approach.

Note: this is a trial protocol, not results — efficacy of caloric restriction in ADPKD remains unproven. Any weight-loss intervention should be undertaken with physician/dietitian guidance; do not attempt aggressive dieting on your own.

Source: American Journal of Nephrology (2026-10-17) · Read more

Estuary Biotherapeutics announced a $103 million launch to develop targeted gene therapies addressing the root cause of ADPKD, with the stated goal of durably halting or reversing the structural and functional manifestations of the disease.

A gene-therapy approach differs from approved symptomatic treatments such as tolvaptan and represents early-stage investment in disease modification. The company is pre-clinical; this is financing/company news rather than efficacy evidence.

Source: Estuary Biotherapeutics press release (2026-10-16) · View release

A Scientific Reports study used single-cell RNA sequencing in Pkd1-deficient mice to identify GPRC5A-positive cyst-lining cell clusters (from the loop of Henle and proximal tubules) with dysregulated Hippo signaling and enhanced unfolded protein response (UPR). Nuclear TFEB and CHOP accumulation increased pro-apoptotic gene expression — TFEB appears to restrict cyst expansion by driving ER stress-induced apoptosis of cyst-lining cells.

TFEB deficiency attenuated apoptosis and accelerated cyst growth; human ADPKD kidney samples mirrored the nuclear TFEB/CHOP findings — suggesting TFEB activation may be an endogenous cyst-limiting mechanism and a potential therapeutic target.

Source: Scientific Reports (2026-10-14) · View article · DOI

SCYNEXIS announced completion of a Phase 1 study of SCY-770, a potential first-in-class selective oral direct AMPK activator designed to address multiple underlying drivers of cyst growth and progression in ADPKD. Phase 1 in healthy volunteers characterized safety, tolerability and pharmacokinetics, with favorable tolerability at higher doses than previously evaluated.

A Phase 2 proof-of-concept study in ADPKD patients remains on track to start in Q4 2026. Note: Phase 1 only establishes short-term safety in healthy participants — it is not evidence of efficacy in ADPKD.

Source: SCYNEXIS press release (2026-10-06) · View release

Clinical Kidney Journal published the SIDIA study: a randomized, double-blind, placebo-controlled two-period crossover trial in 15 adults with ADPKD (mean eGFR 68), comparing empagliflozin 10 mg vs placebo for 14 days each. The primary endpoint (24-h urinary/fractional excretion of phosphate, calcium, magnesium) showed no difference; empagliflozin lowered serum uric acid −26%, raised serum magnesium +5.7%, increased urinary citrate +78.6% (relevant to kidney-stone propensity), reduced blood pressure −4/−7 mmHg, and produced an expected −7.1% eGFR dip; copeptin rose +26%.

No major short-term safety signals were observed, but the sample is small and analyses exploratory. Together with the ongoing STOP-PKD Phase 3 (see Oct 1 item), this addresses the place of SGLT2 inhibitors in ADPKD.

Source: Clinical Kidney Journal (2026-10-02) · View article · DOI

Glasgow-based Mironid announced it has dosed the initial cohorts in the Phase 1 trial of its first-in-class LoAc® small molecule, marking its transition to a clinical-stage company. The dose-escalation study (EudraCT 2025-524899-40-00) evaluates safety, tolerability and pharmacokinetics in healthy volunteers; the single-ascending-dose part enrolls up to 48 participants across six sequential cohorts.

LoAc® targets the underlying biology of ADPKD; initial data are expected next year. Vicente E. Torres (Mayo Clinic Translational PKD Center) endorsed the program. As with all Phase 1 data, tolerability in healthy volunteers is not efficacy evidence.

Source: Mironid press release (2026-10-01) · View release

The investigator-initiated, randomized, double-blind, placebo-controlled multicenter Phase 3 STOP-PKD trial (NCT07280585), led by the University of Cologne, is recruiting ~420 ADPKD patients to assess whether daily dapagliflozin 10 mg (an SGLT2 inhibitor) slows the chronic eGFR slope; secondary endpoints include a composite of 40% eGFR loss, kidney failure or renal death, with an interim safety analysis covering TKV, eGFR and copeptin.

SGLT2 inhibitors are standard of care in CKD, but landmark trials excluded ADPKD patients and current guidelines do not recommend them in ADPKD — this trial aims to close that evidence gap. Completion expected in 2030.

Source: ClinicalTrials.gov NCT07280585 (recruiting since Dec 2025) · View registration

Researchers at the Jared Grantham Kidney Institute (University of Kansas Medical Center) report in JCI Insight that single-nucleus RNA sequencing of human ADPKD kidneys identifies fibroblasts as the predominant source of fibrous ECM. Pirfenidone — approved for idiopathic pulmonary fibrosis — suppressed ECM gene expression, proliferation, migration and contractility of primary human ADPKD renal myofibroblasts in vitro.

In the Pkd1 RC/RC mouse model, pirfenidone reduced renal fibrosis, myofibroblast accumulation and profibrotic signaling, improved kidney function and reduced kidney enlargement; cyst burden fell only in female mice. Preclinical drug-repurposing evidence — no human data yet.

Source: JCI Insight (2026-09-22) · View article · DOI

A BMC Nephrology study of 50 Malaysian ADPKD patients found the Mayo prognostic model (based on height-adjusted total kidney volume, HtTKV, measured by MRI) predicted eGFR with correlation coefficients of 0.954–1.000 (p<0.001) over 24 months; Bland-Altman analysis showed 85.1% accuracy within P30 of measured eGFR.

The authors conclude the tool provides a useful preliminary prediction of disease progression in Southeast Asian ADPKD patients — relevant for Asian populations — while noting larger cohorts are needed for validation.

Source: BMC Nephrology (2026-09-18) · View article · DOI

Kidney International has formally published the French LIPS study (2026;110(4):988-999): 144 adults with stage 2/3 ADPKD were randomized to monthly lanreotide 120 mg or placebo for three years, with iohexol-clearance mGFR slope as the primary endpoint — lanreotide did not slow mGFR decline. An apparent creatinine-eGFR signal was not replicated by cystatin C-eGFR or urinary creatinine clearance, and is considered exploratory rather than a true kidney benefit.

Gastrointestinal adverse events were more frequent with lanreotide, and hypoglycemia occurred in 11.1% vs 1.4% of placebo. An accompanying editorial discusses endpoint measurement ("ending the confusing story of mGFR and eGFR"). Together with the earlier negative Dutch DIPAK-1 trial, evidence for somatostatin analogues slowing kidney decline weakens further.

Source: Kidney International (2026) · DOI · PubMed

A Mayo Clinic team led by Peter Harris reports in the Journal of Clinical Investigation that PC1 loss thins and deforms the tubular basement membrane (TBM) — enriched in heparan sulfate — driving tubule distension preferentially in the distal nephron. The process is driven by a cilia-dependent transcriptional program, with GLIS2 as a key downstream mediator.

On tubule-on-chip and animal models, reducing TBM stiffness amplified Pkd1-null tubule dilation and cyst formation, while raising luminal pressure (ureteral obstruction) triggered an irreversible cystogenic program. The study establishes a TBM-centered biomechanical model of ADPKD and identifies the cilium/TBM axis as a potential therapeutic target.

Source: Journal of Clinical Investigation (2026-09-15) · View article

Mayo Clinic researchers published in the Journal of Clinical Investigation a previously unknown kidney pathway: urate regulates urine concentration independently of vasopressin. This challenges decades of established physiological understanding.

Led by Dr. Fouad Chebib, the study shows that urate — traditionally associated with gout — plays a critical role in kidney water conservation. For ADPKD, this is significant: the only approved drug (tolvaptan) targets the vasopressin V2 receptor, and the urate pathway offers an entirely new therapeutic target.

Source: Journal of Clinical Investigation / CancerIlles (2026-09-11) · View article

Nature Scientific Reports published a study showing that mebendazole, an anthelmintic drug, slows cyst progression and improves renal function in a Pkd1 ADPKD mouse model by disrupting microtubule polymerization.

The study found that microtubule dynamics are enhanced in Pkd1-deficient cells via GSK3β activation. This is the first identification of dysregulated microtubule dynamics as a previously unrecognized mechanism in ADPKD pathogenesis, suggesting mebendazole as a potential drug-repurposing strategy.

Source: Nature Scientific Reports (2026-09-11) · View article · DOI

PYC Therapeutics announced that the first patient has been dosed in the open-label extension study for PYC-003. The extension study provides longer-duration safety and tolerability data, with patients continuing to receive PYC-003 per the original protocols.

PYC-003 is an RNA drug targeting the miR-17 binding site on PKD1 mRNA with a cell-penetrating peptide. 12-month total kidney volume (TKV) data from the Phase 1a/1b program is expected in late 2027, with registrational study data to follow.

Source: Kalkine Media (2026-09-11) · View article

On PKD Awareness Day (Sept 4), the PKD Foundation called for public support of the PKD Cures Act (H.R. 9169) — the first federal legislation in U.S. history devoted exclusively to PKD research. Introduced in June 2026 by bipartisan House members, the bill would expand NIH research, speed clinical trials, and establish a long-term federal research roadmap.

Walk for PKD fundraising events run nationwide through September and October. Since 2000, the walks have raised over $36 million for PKD research. Approximately 500,000 people in the U.S. live with PKD.

Source: PRNewswire / PKD Foundation (2026-09-04) · View article · PKD Cures Act details

CDISC, in partnership with the PKD Foundation and Critical Path Institute, released TAUG-PKD Version 2.0, helping researchers worldwide generate more comparable, reusable, and regulatory-ready data to accelerate discovery for both ADPKD and, for the first time, ARPKD.

Version 1.0 incorporated data from CRISP and HALT-PKD trials and supported the regulatory qualification of total kidney volume (TKV) as a disease progression biomarker for ADPKD.

Source: PKD Foundation (2026-09-04) · View article

A bioRxiv preprint demonstrates that collecting duct-targeted lipid nanoparticles (LNPs) delivering Pkd2 mRNA reversed established cystic disease in Pkd2-deficient mice, restoring renal architecture and reducing fibrosis and inflammation.

A single dose also reduced cyst burden and improved renal function in a Pkd1-deficient model, suggesting the strategy may work across genetic backgrounds. This is the first study showing mRNA replacement therapy directly restoring polycystin expression and reversing formed cysts.

Source: bioRxiv preprint (2026-06-05) · View article

Frontiers in Medicine published a Chinese single-center prospective open-label trial: 89 rapid-progression ADPKD patients on tolvaptan for 2 years showed left kidney TKV mean change of -70.2 mL (6 months) and -47.8 mL (12 months), with stable eGFR and no major hepatic/renal toxicity.

80% had family history, 40% had polycystic liver disease, 65.6% had hypertension. Most common daily doses: 60mg (31.1%) and 45mg (26.7%). This provides local Chinese evidence supporting tolvaptan efficacy and safety.

Source: Frontiers in Medicine (2026-03-12) · View article · DOI

Under China's "pilot access" policy, Shanghai Jiao Tong University Affiliated Ruijin Hospital Hainan (Boao Lecheng Pilot Zone) has officially introduced tolvaptan for ADPKD, issuing the first domestic prescription.

The first patient is a 53-year-old man from Zhejiang, diagnosed with ADPKD for over 20 years. He started tolvaptan in February 2026 under Dr. Xie Jingyuan's team, titrated to 45mg AM / 15mg PM by July. The drug is not yet commercially available in China — it is approved only within the Lecheng Pilot Zone. Indication: ADPKD with CKD showing signs of rapid progression, to delay cyst and kidney function decline.

The model uses dual-hospital coordination: comprehensive evaluation at Ruijin Shanghai, medication at Ruijin Hainan, with ongoing monitoring of kidney function and electrolytes.

Source: Sina Finance / CCTV Media (2026-09-09) · Sina Finance · CCTV Media

PYC Therapeutics presented PYC-003 Phase 1 safety data at the ANZSN annual meeting. PYC-003 is an RNA drug targeting the miR-17 binding site on PKD1 mRNA, with a cell-penetrating peptide to enhance kidney cell uptake.

All single ascending dose cohorts (healthy volunteers + ADPKD patients) showed zero treatment-related serious adverse events. No changes in serum electrolytes, creatinine, liver function, or renal injury biomarkers (KIM-1, NGAL).

Next: Phase 1a SAD data expected H2 2026, Phase 1b MAD and open-label extension data expected CY 2027. ADPKD affects ~12.5 million people globally, with ~95% currently without treatment options.

Source: StockwireX (2026-08-31) · View article

A Yale team published a study in the Journal of Clinical Investigation identifying upstream open reading frames (uORFs) in the PKD1 gene that limit polycystin-1 (PC1) translation efficiency.

In genetically engineered mouse models, disrupting these uORFs increased PC1 levels 2-4 fold. This supports the therapeutic strategy of "boosting polycystin production" rather than "fixing the mutant gene," consistent with current anti-miR-17 oligonucleotide and pharmacochaperone approaches.

Source: Medical Xpress (2026-08-25) · View article · JCI paper

The PKD Foundation published a comprehensive review of the current ADPKD therapeutic pipeline across four directions:

1. Gene-directed therapies: Farabursen (Novartis, anti-miR-17, Phase 3 initiation being scheduled), PYC-003 (PYC Therapeutics), VX-407 (Vertex pharmacochaperone, Phase 2a AGLOW trial ongoing).

2. Metabolic pathways: SGLT2 inhibitors (dapagliflozin + tolvaptan combination showed additive benefit), empagliflozin EMPA-PKD trial, GLP-1 receptor agonists.

3. Paracrine signaling: PAPP-A inhibitors significantly reduced cyst growth and preserved kidney function across three preclinical mouse models.

4. Gene editing/gene therapy: Single-treatment curative therapies becoming a realistic possibility.

The review emphasizes two key conceptual shifts: ADPKD is "dosage-dependent" not "on or off" — even partial restoration of polycystin levels may be therapeutic; and early cystic changes may be reversible.

Source: Life Science Daily (2026-08-18) · View article

South Korea's Mezzion Pharma announced expanding Udenafil (a PDE5 inhibitor originally developed for Fontan patients) into ADPKD, proceeding directly to Phase 2b trials in Korea and the US.

Animal model results from Mayo Clinic collaboration showed: 50-60% cyst reduction, significant BUN improvement (P<0.001), and improvement in cardiac hypertrophy indicators. Efficacy was verified stepwise from cells to kidney tissue to live animal models.

Source: EDAILY (2026-08-08) · View article

SCYNEXIS initiated a Phase 1 study of SCY-770, a first-in-class oral direct AMPK activator. Preclinical data demonstrated inhibition of cyst cell proliferation and reduction of cyst growth in the kidney.

The drug has a well-characterized safety profile in over 270 clinical trial participants. Phase 1 dose-optimization data expected Q3 2026, with Phase 2 proof-of-concept initiation planned for Q4 2026.

Source: SCYNEXIS press release (2026-06-30) · View article

The ANCHOR study (Phase 2) by AbbVie and Calico Life Sciences is enrolling. The trial spans 231 sites across 9 countries, planning to enroll 240 adult ADPKD patients.

Dosing: intravenous ABBV-CLS-628 or placebo every 4 weeks for 92 weeks. Primary endpoint: rate of change in total kidney volume (TKV) at Week 96. Secondary endpoints include eGFR change.

Source: ClinicalTrials.gov (updated 2026-09-01) · View article

An open-label randomized controlled crossover trial (27 ADPKD patients) evaluated the additive effect of the SGLT2 inhibitor dapagliflozin in patients already on tolvaptan.

Results: Adding dapagliflozin significantly attenuated the eGFR (cystatin C) decline slope (P=0.003) and 6-month TKV change (-0.44% vs +5.04%, P=0.01). This suggests SGLT2 inhibitors may provide additional benefit on top of tolvaptan.

Source: Kidney International Reports (2025) · View article