Farabursen

Last updated

Farabursen
Clinical data
Other namesRGLS8429
Routes of
administration 		Subcutaneous injection
Legal status
Legal status
  • Investigational
Identifiers
CAS Number
UNII

Farabursen (development code RGLS8429) is an investigational oligonucleotide drug developed by Regulus Therapeutics for the treatment of autosomal dominant polycystic kidney disease (ADPKD). [1] [2] The drug is designed to inhibit microRNA-17 (miR-17) and preferentially targets the kidney. [3]

Contents

In April 2025, Novartis announced plans to acquire Regulus Therapeutics to advance farabursen's development, [4] with the acquisition completed in June 2025. [5]

Mechanism of action

Farabursen is a next-generation antisense oligonucleotide that works by inhibiting microRNA-17 (miR-17). [3] The drug is designed with preferential kidney distribution, allowing it to target the site of disease more effectively. [1]

MicroRNA-17 normally suppresses the expression of the PKD1 and PKD2 genes, which produce polycystin-1 (PC1) and polycystin-2 (PC2) proteins respectively. [6] These polycystin proteins play a crucial role in regulating kidney cell growth and preventing cyst formation. In ADPKD, mutations in these genes result in reduced protein levels, leading to uncontrolled cyst growth. By inhibiting miR-17, farabursen aims to increase the production of PC1 and PC2 proteins, potentially slowing or halting disease progression. [6]

Clinical trials

Phase 1 studies

A Phase 1 single ascending dose (SAD) study was completed in September 2022. [7] The trial demonstrated that farabursen had a favorable safety and pharmacokinetic profile, with the drug being well-tolerated and no serious adverse events reported. Plasma exposure was approximately linear across the four tested doses. [8] [9]

Phase 1b multiple ascending dose study

The Phase 1b multiple ascending dose (MAD) study (NCT05521191) was a double-blind, placebo-controlled trial that evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of farabursen in adult patients with ADPKD. [10] The primary endpoints measured changes in urinary polycystin-1 (PC1) and polycystin-2 (PC2) levels, while exploratory endpoints examined changes in height-adjusted total kidney volume (htTKV) and overall kidney function. [6]

See also

References

  1. 1 2 "Novartis to acquire Regulus Therapeutics and farabursen, an investigational microRNA inhibitor to treat ADPKD, the most common genetic cause of renal failure" (Press release). Novartis. 1 May 2025.
  2. ↑ Fang C, Norouzi S, Garimella PS (September 2025). "Therapies in autosomal dominant polycystic kidney disease: beyond tolvaptan". Current Opinion in Nephrology and Hypertension. 34 (5): 368–374. doi:10.1097/MNH.0000000000001101. PMID   40726372.
  3. 1 2 "Regulus Therapeutics Announces Successful Completion of its Phase 1b Multiple-Ascending Dose (MAD) Clinical Trial of Farabursen (RGLS8429) for the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)" (Press release). Regulus Therapeutics. 27 March 2025.
  4. ↑ "Regulus Therapeutics Enters into Agreement to be Acquired by Novartis AG" (Press release). Regulus Therapeutics. 30 April 2025.
  5. ↑ "Novartis Completes Acquisition of Regulus Therapeutics" (Press release). Novartis. 25 June 2025.
  6. 1 2 3 "RGLS8429 Increases Urinary PC1 and PC2 and May Reduce... : Journal of the American Society of Nephrology". LWW. doi:10.1681/ASN.2024w1p (inactive 6 November 2025). Archived from the original on 29 April 2025. Retrieved 6 November 2025.{{cite journal}}: CS1 maint: DOI inactive as of November 2025 (link)
  7. ↑ Regulus Therapeutics Inc. (25 August 2025). A Phase 1, Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics of RGLS8429 (Report). clinicaltrials.gov.
  8. ↑ "Regulus Therapeutics Announces Positive Topline Data from the Second Cohort of Patients in its Phase 1b Multiple-Ascending Dose (MAD) Clinical Trial of RGLS8429 for the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)". BioSpace. 12 March 2024. Retrieved 6 November 2025.
  9. ↑ "Regulus Therapeutics Announces First Patient Dosed in Phase 1b Multiple-Ascending Dose (MAD) Clinical Trial of RGLS8429 for the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)" (Press release). Regulus Therapeutics. 2 November 2022.
  10. ↑ Regulus Therapeutics Inc. (28 May 2025). A Phase 1b, Double-Blind, Placebo-Controlled, Multiple Ascending Dose and an Open-Label Fixed-Dose Study in Patients With Autosomal Dominant Polycystic Kidney Disease to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of RGLS8429 (Report). clinicaltrials.gov.
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