Liposomal tacrolimus led to improvements in hematuria, bleeding sites on cystoscopy, microscopic urine analysis for red blood cells, and urinary symptoms.
Liposomal tacrolimus (LP-10) demonstrated promising efficacy and safety in patients with hemorrhagic cystitis (HC), according to results of a phase 2a study published in the Journal of Urology and Nephrology.1,2
The findings showed that LP-10 led to improvements in hematuria, bleeding sites on cystoscopy, microscopic urine analysis for red blood cells (RBCs), and urinary symptoms. LP-10 was also well tolerated; investigators did not report any treatment-related severe or serious adverse events (AEs).
"The peer-reviewed publication of our phase 2a study results is a milestone achievement for Lipella. It underscores the significance of our clinical program and LP-10's potential as a first-in-class treatment for the cancer survivor community with hemorrhagic cystitis," Jonathan Kaufman, PhD, chief executive officer, Lipella, the developer of LP-10, stated in a press release.1
The multicenter phase 2a dose-escalation study enrolled patients with refractory moderate to severe sterile HC (grades 2-4) for ≥3 months. Patients had 1 or more incident of hematuria either with or without blood clot.
Overall, 13 patients enrolled and completed the study between February 2021 and October 2022. Patients received up to 2 intravesical instillations of LP-10 at one of three doses: 2 mg (n = 4), 4 mg (n = 4), and 8 mg (n = 5). The median age was 77 years (range, 65-89), 72 years (range, 63-81), and 48.5 years (range 25-72) for the 3 cohorts, respectively. All patients were male.2
Across the cohorts, the most common prior treatments for HC reported were hyperbaric oxygen therapy (n = 6) and bladder fulguration (n = 5). Ten patients received both instillations, while 3 patients felt better after the first dose and opted not to receive the second.2
Across all patients, the number of patients negative for hematuria on urine dipstick rose to 7 following treatment versus only 2 at baseline. At 2 weeks’ follow-up, a statistically significant improvement from baseline in the number of bleeding sites on cystoscopy was observed in the 2 mg (P = .16), 4 mg (P = .06), and 8 mg (P = .04) cohorts.
Data on RBC count on urine microscopy was available for 11 patients. An improvement over baseline in the RBC per HPF count on urine microscopy was observed across all dose cohorts. Of the 11 patients, there were 8 with 0-4 urinary RBCs per HPF on microscopy at 1 week following treatment compared with 4 patients at baseline. Further, the 3 remaining patients did not have more than 10 to 24 RBCs per HPF at 1 week after treatment.2
There was also a statistically significant improvement vs baseline in the number of incontinence episodes per 3-day period observed in the 4- and 8-mg cohorts.
Regarding safety, 6 (46%) of the 13 patients experienced a total of 12 adverse events (AEs). Most AEs were mild and all resolved within a few hours or days. There were 3 patients who experienced drug-related AEs, which consisted of artificial urinary sphincter malfunction, dysuria, and bladder spasms. AEs related to instillation that were reported included urinary tract infection, dysuria, bladder spasms, and urinary urgency were reported.2
"LP-10 has received Orphan Disease Designation from the FDA for the treatment of hemorrhagic cystitis, a potentially fatal disease with great unmet need and no currently approved drug treatment. We are scheduled to have a Type-C meeting with FDA in Q4 and plan to share details on those discussions shortly thereafter. We currently expect to initiate our phase 2b clinical trial for LP-10 in January 2024," Michael Chancellor, MD, chief medical officer, Lipella, stated in the press release.1
1. Lipella Pharmaceuticals' Phase 2a Clinical Study Results Published in the Journal of Urology and Nephrology. Published online and accessed September 21, 2023. https://tinyurl.com/mwx3ywux
2. Hafron J, Breyer BN, Joshi S, Smith C, Kaufman MR, Okonski J, Chancellor MB. Intravesical liposomal tacrolimus for hemorrhagic cystitis: a phase 2a multicenter dose-escalation study [published online ahead of print September 19, 2023]. Int Urol Nephrol. doi: 10.1007/s11255-023-03783-y