Elmiron (pentosan polysulfate sodium) / Paradigm Biopharma, ReqMed, Bene-Arzneimittel - LARVOL DELTA

BPS Symptom Load during Pentosane Polysulfate Sodium Treatment in Real Life in France. (PubMed, Fr J Urol) - "Safety of PPS was confirmed. PPS treatment was associated with improvement of BPS symptoms like urinary frequency, pain and patient perception of BPS-related problems. Monitoring every 6 months was confirmed to enable timely treatment modifications."

Journal • Gynecology • Inflammation • Interstitial Cystitis • Musculoskeletal Pain • Pain • Urology

Pentosan polysulfate maculopathy: clinical considerations, pathobiology, and causality. (PubMed, Prog Retin Eye Res) - "Consequently, there is a pressing need for increased recognition of PPS toxicity and further understanding of disease mechanisms. This review summarizes the clinical characteristics of PPS maculopathy, evaluates its public health impact, explores potential pathogenic mechanisms, and presents a compelling case for causality using clinical, laboratory, and epidemiological evidence."

Journal • Review • Immunology • Interstitial Cystitis • Macular Degeneration • Musculoskeletal Pain • Ophthalmology • Osteoarthritis • Pain • Retinal Disorders • Rheumatology

Colopathy associated with pentosan polysulfate use. (PubMed, Front Pharmacol) - "Histopathologic findings suggest a novel drug-associated colopathy, with some subjects necessitating colectomy for dysplasia. Further investigation into the causality of this association is warranted."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Interstitial Cystitis

Sentiments of Individuals with Interstitial Cystitis/Bladder Pain Syndrome Toward Pentosan Polysulfate Sodium: Infodemiology Study. (PubMed, JMIR Form Res) - "As IC/BPS remains a complex syndrome, this study highlights the value of patient-led discussions in informing treatment decisions. Furthermore, these findings suggest that health care providers might benefit from considering the insights shared on peer-to-peer forums to better understand individual preferences, concerns, and expectations."

Journal • Interstitial Cystitis • Macular Degeneration • Musculoskeletal Pain • Pain • Retinal Disorders

Pentosan polysulfate sodium maculopathy: Final analysis of a prospective cohort, updated review, and association with inflammatory bowel disease. (PubMed, Surv Ophthalmol) - "Vigilant surveillance of patients receiving this potentially harmful drug is critical. We review the recommended screening guidelines, the pathophysiology and MMI spectrum of disease, the differential diagnosis including MMI clues to an accurate diagnosis, and the progression of retinopathy that can take place despite discontinuation of the drug, emphasizing the critical importance of early detection of toxicity."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Interstitial Cystitis • Macular Degeneration • Retinal Disorders

Potential New Phenotypic Presentation of Pentosan Polysulfate Sodium Maculopathy. (PubMed, J Vitreoretin Dis) - "In this case, a review of pertinent medications assisted in making the diagnosis of toxic maculopathy. Proper diagnosis and prompt discontinuation of the inciting medication are necessary to avoid the risk for potentially irreversible retinal damage and vision loss."

Journal • Achromatopsia • Age-related Macular Degeneration • Inherited Retinal Dystrophy • Interstitial Cystitis • Macular Degeneration • Ophthalmology • Retinal Disorders

Update on Retinal Drug Safety: Proceedings of the ASRS ReST Committee Webinar Part 1. (PubMed, J Vitreoretin Dis) - " Topics reviewed in the webinar included pentosan polysulfate sodium (Elmiron) maculopathy, intraocular pressure elevation reported with the aflibercept prefilled syringe (PFS), and brolucizumab-associated inflammation with occlusive retinal vasculitis. Retinal toxicity related to intraoperative medications was reviewed, including hemorrhagic occlusive retinal vasculitis after intraocular vancomycin, dilution errors with intravitreal aminoglycosides, inadvertent overdoses of cefuroxime after cataract surgery, and toxic posterior segment syndrome after dropless cataract surgery using compounded triamcinolone-moxifloxacin...The ASRS ReST Committee collects data from its website reporting system to inform members about up-to-date pharmaceutical and device safety concerns. Recently, a webinar was used to inform members of pigmentary maculopathy associated with pentosan polysulfate sodium, safety regarding the aflibercept PFS, intraocular inflammation and occlusive retinal..."

Journal • Cataract • Hematological Disorders • Inflammation • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Vasculitis

ELMIRON: A PEEK INTO THE MEDICOLEGAL WORLD (AUA 2024) - "This convenient sample of product liability lawsuits related to PPS use provides insight into the rise in adverse event reporting surrounding the FDA "Black Box warning" in June 2020. Interestingly, no prescribing medical provider was listed as a defendant in any of the 26 legal claims. Ultimately, we plan to review the multidistrict class action lawsuit in New Jersey with over 1,800 claims pending as of October 2023."

Interstitial Cystitis • Macular Degeneration • Musculoskeletal Pain • Pain • Retinal Disorders

INSIGHT INTO ELMIRON: AN IN-DEPTH EXAMINATION OF OCULAR ADVERSE EVENTS (AUA 2024) - "Although this data set has known limitations, FAERS is a publicly accessible database that is useful in monitoring adverse events in "real-time. " These data indicate that female patients are disproportionately affected by ocular adverse eventsassociated with PPS, which is consistent with case series from ophthalmology literature (Leug, 2021). Interestingly, the peak in FAERS database filings for these adverse events coincides with a class action lawsuit certified in 2020, perhaps suggesting a legal motivation behind these filings."

Adverse events • Alopecia • Gastrointestinal Disorder • Interstitial Cystitis • Macular Degeneration • Musculoskeletal Pain • Ophthalmology • Pain • Retinal Disorders

Incidence and Risk of Retinopathy in Patients With and Without Interstitial Cystitis and Pentosan Polysulfate Sodium Use. (PubMed, J Vitreoretin Dis) - " Patients with IC had greater incidence and risk of retinopathy. PPS use further increased the incidence and risk of retinopathy."

Journal • Inherited Retinal Dystrophy • Interstitial Cystitis • Macular Degeneration • Retinal Disorders • Retinitis Pigmentosa

Further advances in identification of pentosan polysulfate monosaccharide composition by NMR. (PubMed, J Pharm Biomed Anal) - "Several publications have recently proposed NMR spectroscopy to evaluate the critical quality attributes (CQA) of pentosan polysulfate sodium (PPS), the active ingredient of Elmiron™ approved to treat interstitial cystitis...The newly identified cross-peaks were integrated into an updated quantitative NMR method. Finally, we demonstrated that an in-depth PPS analysis can be obtained using NMR instruments at medium magnetic fields (500 MHz/600 MHz), commonly available in pharmaceutical industries."

Journal • Interstitial Cystitis

"Elmiron?" (@ArpanUppal5)

Progression of Pentosan Polysulfate Sodium (PPS) Maculopathy in a Prospective Cohort. (PubMed, Am J Ophthalmol) - "Eyes with baseline PPS maculopathy all exhibited remarkable progression with qualitative and quantitative multimodal imaging analysis despite drug discontinuation. Disease progression may be attributed to underlying inner choroidal ischemia or RPE impairment."

Journal • Cardiovascular • Macular Degeneration • Retinal Disorders

Macular Hole in a patient with Pentosan Polysulfate Maculopathy. (PubMed, Retin Cases Brief Rep) - "PPS-related maculopathy can lead to severe retinal atrophy and a subsequent degenerative macular hole. A high index of suspicion is required for early detection and cessation of drug to prevent this irreversible vision loss."

Journal • Age-related Macular Degeneration • Interstitial Cystitis • Macular Degeneration • Retinal Disorders

Pentosan polysulfate sodium (Elmiron) maculopathy: a genetic perspective. (PubMed, Retina) - "Pentosan polysulfate maculopathy is not associated with Mendelian IRD genes. However, several AMD risk alleles were identified to be associated with maculopathy compared to their frequency in the normal population. This suggests a role for genes in disease pathology, particularly the alternative complement pathway. These findings would benefit from further investigation to understand the risk of developing maculopathy in taking pentosan polysulfate."

Journal • Age-related Macular Degeneration • Inherited Retinal Dystrophy • Macular Degeneration • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

The effect of pentosan polysulfate sodium for improving dyslipidaemia and knee pain in people with knee osteoarthritis: A pilot study. (PubMed, Osteoarthr Cartil Open) - "To evaluate the efficacy and safety of pentosan polysulfate sodium (PPS, Elmiron®) for dyslipidaemia and knee osteoarthritis (OA) related symptoms...The most common AEs were positive faecal occult blood tests, followed by headache and diarrhoea. The findings suggest that PPS has promising effects on improving dyslipidaemia and symptomatic pain relief in people with knee OA."

Clinical • Dyslipidemia • Immunology • Metabolic Disorders • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Characterization of pentosan polysulphate patients for development of an electronic medical record screening and alert system for ophthalmic monitoring. (PubMed, Can J Ophthalmol) - "An EMR support tool can improve referral rates of PPS maculopathy screening with an ophthalmologist and may serve as an efficient method for longitudinal screening of this condition with the added benefit of informing pentosan polysulphate prescribers about this condition. Effective screening and detection may help determine which patients are at high risk for this condition."

Journal • Interstitial Cystitis • Macular Degeneration • Ophthalmology • Retinal Disorders

"Have had occasional response to elmiron, but anecdotal" (@tyldesley_scott)

"Role for Elmiron ?" (@PPendyalaMD)

Age-Related Macular Degeneration Masquerade: A Review of Pentosan Polysulfate Maculopathy and Implications for Clinical Practice. (PubMed, Asia Pac J Ophthalmol (Phila)) - "Pentosan polysulfate (PPS) sodium (Elmiron) is the only Food and Drug Administration (FDA)-approved oral medication to treat interstitial cystitis, also known as bladder pain syndrome...We also compare PPS maculopathy to age-related macular degeneration, explain why differentiating between the 2 is clinically important, and highlight avenues for further research. Finally, we highlight the paucity of data on patients of color and why this lack of understanding may impact patient care."

Journal • Review • Age-related Macular Degeneration • Diabetes • Inherited Retinal Dystrophy • Interstitial Cystitis • Macular Degeneration • Metabolic Disorders • Musculoskeletal Pain • Ophthalmology • Otorhinolaryngology • Pain • Retinal Disorders

Radiation Cystitis Treated With Pentosan Polysulfate Sodium Trial (clinicaltrials.gov) - P2/3 | N=72 | Recruiting | Sponsor: National Taiwan University Hospital | Not yet recruiting ➔ Recruiting

Enrollment open

Redefining the Spectrum of Pentosan Polysulfate Retinopathy: Multimodal Imaging Findings from a Cross-Sectional Screening Study. (PubMed, Ophthalmol Retina) - "Findings from masked grading of multimodal imaging at a centralized reading center suggest a wider phenotypic spectrum of structural abnormalities among patients taking PPS. Macular changes selectively involve the RPE and outer retina, with a range of findings often seen beyond the arcades. The subtle and atypical findings in this cohort should prompt clinicians to consider lowering the threshold for diagnosing PPS retinopathy."

Journal • Diabetic Retinopathy • Interstitial Cystitis • Ophthalmology • Retinal Disorders

Paradigm Biopharmaceuticals Initiates a Phase 3 Clinical Trial in Knee Osteoarthritis Across the U.S (PRNewswire) - "Paradigm Biopharmaceuticals...is announcing...the official launch of their U.S. clinical trial program with an estimated 56 planned clinical trial locations nationwide for the conduct of the pivotal phase 3 trial to support registration of Pentosan Polysulfate Sodium (PPS) for osteoarthritis (OA) of the knee....The purpose of this study is to measure the change in pain and function with subcutaneous injections of PPS compared with subcutaneous injections of placebo in participants with kOA pain....The primary endpoint in the pivotal study is a change from baseline at Day 56 in WOMAC® pain with secondary outcomes including change from baseline at multiple time points out to day 168 in WOMAC® Pain and Function, Patient Global Impression of Change and Quality of Life."

Trial status

Prevention and Management of Intravesical BCG-related Lower Urinary Tract Symptoms (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: Sir Mortimer B. Davis - Jewish General Hospital | N=100 ➔ 3 | Trial completion date: Dec 2020 ➔ Feb 2022 | Suspended ➔ Terminated | Trial primary completion date: Sep 2020 ➔ Feb 2022; Given the updated precautions on Elmiron as well as the risk benefit profile, we have decided to terminate the study.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • IL10 • IL2

Radiation Cystitis Treated With Pentosan Polysulfate Sodium Trial (clinicaltrials.gov) - P2/3 | N=72 | Not yet recruiting | Sponsor: National Taiwan University Hospital

New P2/3 trial