Oakland University William Beaumont School of Medicine
Introduction: Radiation used to treat prostate, colon, uterine, cervical and other pelvic cancers can cause chronic, painful urinary inflammation and hemorrhagic cystitis (HC). The blood loss associated with hemorrhagic cystitis can lead to surgery and can be fatal. Lipella Pharmaceuticals received orphan disease designation for HC and recently completed a phase 2a clinical trial of LP-10 for the treatment of HC. Methods: The LP-10 Phase 2a clinical trial was a multi-center, dose-escalation study of intravesical instillation of liposomal formulation of tacrolimus at 2mg, 4 mg and 8mg. The study recruited 13 subjects with moderate to severe refractory hemorrhagic cystitis. These subjects were treated with up to two courses of LP-10 bladder instillations (clinicaltrials.gov: NCT01393223). Results: Fifteen subjects were screened (14 male and 1 female) and 13 enrolled. All enrolled subjects were male with mean age 67 (range 25-89 years old) with a history of prostate cancer (n=9), bladder cancer (n=2) and lymphoma (n=2). Mean duration of HC was 4 years and ranged from 1-14 years. All subjects tolerated LP-10 instillations and completed the study without report of product related serious adverse events. LP-10 pharmacokinetic analysis demonstrated short duration of systemic uptake. A dose response was observed. Responder analysis evaluating cystoscopy, hematuria, and symptoms noted complete response in 3 subjects, partial response in 7 subjects and no response in 3 subjects. (NR=“no response”, PR=“partial response”, CR=“complete response”)(normalized rank, 0 to 9)(Figure 1). Conclusions: The results of the Phase 2a study demonstrated safety and a signal of efficacy with dose response of LP-10 for the treatment of refractory moderate to severe HC. This is the first successfully completed trial for cancer survivors with HC and more research is needed to develop a drug treatment for hemorrhagic cystitis, a disease with great unmet need. SOURCE OF Funding: Lipella Pharmaceuticals, Inc.
